Molecular Medicine Program Faculty - 12/16/2009 04:39:55 pm ...
-
Upload
brucelee55 -
Category
Documents
-
view
3.898 -
download
3
Transcript of Molecular Medicine Program Faculty - 12/16/2009 04:39:55 pm ...
Taiwan International Graduate Program
Molecular Medicine Program
Faculty
Institute of Biomedical Sciences /
National Yang Ming University
Taiwan International Graduate Program
Molecular Medicine Program
Institute of Biomedical Sciences
Faculty
2
Name in Chinese:張程
Name in English:Chang, Chen
Education: University of Alabama at Birmingham
Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei
Title:Research Fellow, Institute of Biomedical Sciences, Academia Sinica
Tel:886-2-2652-3032, 886-2-2789-9027
Fax:886-2-2788-7641
My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/cchang_c.htm
E-mail:[email protected]
Fields of Specialty: Functional MRI/S , Neuroscience
Research Description:
My research focus primarily on the development and application of magnetic resonance imaging
and spectroscopy techniques for the study of brain metabolic, functional and structural alterations in a
variety of cerebral diseases. Specific goals include: 1) developing and validating diffusion and
perfusion MRI to evaluate the changes in cerebral hemodynamics as a result of brain damage; 2)
combining BOLD-, diffusion tensor- and manganese- MRI to study the functional connectivity in rat
brains; 3) developing molecular imaging techniques in studying specific biological pathways, and cell
and gene therapy; 4) developing MR microscopy at cellular resolution to follow key intercellular and
intracellular events; and 5) developing in vivo localized 1H NMR spectroscopy to investigate the
biochemical and physiological integrity of the brain.
We have established a functional and micro-magnetic resonance imaging center (FMIC) core
facility in 2002 to serve the Medical Genomics Program. The core is dedicated to: (1) provide state of
the art MRI equipments and comprehensive MR technical support, including experimental design,
3
targeted technology development and imaging data analysis; (2) promote collaborative links between
the MR and basic science research, and (3) educate and train researchers, fellows, and students in the
use of MR imaging technologies in biomedical research. FMIC provides cutting-edge magnetic
resonance techniques, emphasizing on providing anatomical, biochemical, functional, genetic and
pharmacological information in vivo for small animals.
Selected Recent Publication:
1. Chang, C. and Shyu, B. C. A fMRI Study of Brain Activations During Non-noxious and
Noxious Electrical Stimulatiion of the Sciatic Nerve of Rats. Brain Res., 2001; 897:71-
81..
2. Sun, S. W.; Song, S. K.; Hong, C. Y.; Chu, W. C.; and Chang, C. Improving Relative
Anisotropy Measurement using Directional Correlation of Diffusion Tensors. Mag.
Reson. Med., 2001; 46:1079-1087.
3. Lin, T. N.; Sun, S. W.; Cheung, W. M.; Li, Fuhai and Chang C. Dynamic Changes in
Cerebral Blood Flow and Angiogenesis after Transient Focal Cerebral Ischemia in Rats:
Evaluation with Serial MRI. Stroke, 2002; 33: 2985 - 2991.
4. Song, S.K.; Sun, S.W.; Ramsbottom, M.J.; Chang, C.; Russell, J. and Cross, H.
Dysmyelination Revealed through MRI as Increased Radial (But Unchanged Axial)
Diffusion of Water. NeuroImage, 2002; 17:1429-1436.
5. Sun, S. W.; Song, S. K.; Hong, C. Y.; Chu, W. C.; and Chang, C. Directional correlation
characterization and classification of white matter tracts: Magn. Reson. Med. 2003;
49:271-275.
6. Lee, W. T. and Chang, C. Magnetic Resonance Imaging and Spectroscopy in Assessing 3-
Nitropropionic Acid-Induced Brain Lesions: Animal Model of Huntington's Disease.
Progress in Neurobiology 2004, 72:87-110.
7. Shyu, B.C.; Lin, C. Y.; Sun, J.J.; Chen, S. L. and Chang, C. BOLD response to direct
thalamic stimulation reveals functional connection of the medial thalamus and anterior
cingulate cortex in the rat. Magn. Reson. Med (in press).
8. Shyu, B.C.; Lin, C. Y.; Sun, J.J.; Chen, S. L.; Sylantyeva, S.and Chang, C. A method for
direct thalamic stimulation in fMRI studies using a glass-coated carbon fiber electrode. J.
Neuro. Methods (in press).
4
Name in Chinese:常蘭陽
Name in English:Lan-Yang Ch’ang
Education:Vanderbilt University
Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei
Title:Associate Research Fellow, Institute of Biomedical Sciences, Academia Sinica
Tel:886-2-2652-3940, 886-2-2789-9128
Fax:886-2-2785-8847
My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/lychang_c.html
E-mail:[email protected]
Fields of Specialty:Genomics, Bioinformatics
Research Description:
Our research objective is to dissect the complexity of human biology from the perspectives of
genome, transcriptome and proteome. It is thus of critical importance to establish in the laboratory
appropriate technological competence that enables the study of large-scale biology. The ultimate goal
of this undertaking is to understand better how the complex genetic networks operate and govern all
aspects of biological processes in living organisms. The human genomic sequence, completed in 2003,
provides us a genetic framework for examining the complexity of life. The functionality of each
annotated gene will be described in the context of its biological role under normal physiology or in
response to external factors. In the revolutionary era of new biology, this knowledge foundation will
greatly assist us to identify genes involved in various disease processes for future development of
diagnostic, therapeutic and preventive measures.
Our ongoing research efforts cover three major areas of interest:
5
(1.) Functional Genomics
A complexity reduction technology has been developed for profiling the expressed genes in normal
and diseased conditions, and during early embryogenesis. DNA microarray has also been set up for
the analysis of gene expression pattern. Recently we have begun to characterize the function of
novel genes in the human genome by the molecular and cellular approaches as well.
(2) Bioinformatics
We have developed an alternative algorithm –CRASA– for mapping the expressed sequence tags
(ESTs) to the genome, which enables us to annotate the transcribed sequence in the public
databases. A fully automated gene annotation pipeline has been established for large-scale EST-to-
genome mapping. In addition we are in process of developing a new algorithm for the identification
of evolutionarily conserved syntenic markers in the mammalian genomes.
(2.) Human Genetic Diversity
Sequence variation among different individuals accounts for 0.1% of our genomic content. Yet, the
biological consequence, or phenotype, is often dictated by the polymorphic genotypes functioning
alone or interacting with environmental factors. Currently, we are developing a haplotyping
technique to address the correlation between genotype and phenotype using the human disease
model.
Selected Recent Publication:
1. J.-Y. Chiu, C.-S. Liu, L.-Y. Ch'ang and W.-C. Lin. Comparative Ping-pong Analysis of
EST Databases. J. Genet. & Mol. Biol. 2:94-100, 2002.
2. S.-J. Wei, W.-K. Yang, L.-Y. Ch'ang, D.-M. Yang, Y.-M. Hung and W.-C. Lin.
Combination Gene Therapy of Cancer: Granulocyte-Macrophage Colony Stimulating
Factor Enhances Tumor Regression Induced by Herpes Simplex Virus Thymidine
Kinase/ Ganciclovir "Suicidal" Treatment in a Mouse Tumor Model. J. Genet. & Mol.
Biol. 3:194- 208, 2002.
3. T.-J. Chuang, W.-c. Lin, H.-C. Lee, C.-W. Wang, K.-L. Hsiao, Z.-H. Wang, D. Hsieh,
S.C. Lin and L.-Y. Ch'ang. A Complexity Reduction Algorithm for Analysis and
Annotation of Large Genomic Sequence. Genome Res. 13:313-322, 2003
4. Lin, T.-Y., Twu, N.-K., Ho, M.-S., Ch'ang, L.-Y., and Lee, C.-Y. Enterovirus 71
outbreak, Taiwan: occurrence and recognition. J. Emerging Inf. Dis. 9:291-293, 2003.
5. Liu, C.C. and Ch'ang, L.-Y. Down-regulation of human NDR gene in megakaryocytic
6
differentiation of erythroleukemia K562 cells. J. Biomed. Sci. 11:104-111, 2004.
7
Name in Chinese:趙麗洋
Name in English:Chau, Lee-Young
Education:University of Kentucky
Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei
Title:Research Fellow, Institute of Biomedical Sciences, Academia Sinica
Tel:886-2-2652-3931, 886-2-2789-9137
Fax:886-2-2785-8847
My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/ lychau_c.html
E-mail:[email protected]
Fields of Specialty:Cardiovascular Diseases, Inflammation, Gene therapy
Research Description:
Cardiovascular diseases are the leading cause of morbidity and mortality in developed countries.
As the worldwide incidence of cardiac diseases continues to increase steadily, fully understanding the
pathological mechanisms underlying the disease development at the molecular and genetic levels as
well as developing new successful approaches for the therapeutic intervention imposes a great
challenge in biomedical research nowadays. The research interests in my laboratory include the
development of gene-based therapeutic treatment for the diseases, and the identification of disease-
related genes using ENU-mutagenesis approach. Besides, we are very interested in the study of the
cytoprotective function of heme oxygenase-1 (HO-1), which is a stress-inducible enzyme to catalyze
the degradation of prooxidant heme to produce carbon monoxide (CO), bilirubin and free iron. Recent
studies from our liaboratory and others have demonstrated that HO-1 plays an important role in iron
homeostasis and exerts potent anti-inflammatory effect via CO, although the mode of action is not yet
clear. Experiments are ongoing to elucidate the signaling network underlying the protective function
8
of HO-1. Furthermore, the therapeutic potential of HO-1 in treating cardiovascular diseases was
explored in animal models.
Selected Recent Publication:
1. Lee T-S., Yen, H-C., Pan, C-C. and Chau, L-Y. The role of interleukin 12 in the
development of atherosclerosis in apoE-deficient mice. Arterioscler. Thromb. Vasc.
Biol. 19: 734-742, 1999.
2. Pang, J-H.S. and Chau, L-Y. Copper-induced apoptosis and immediate early gene
expression in murine J774.A1 macrophages. Atherosclerosis. 146: 45-52, 1999.
3. Ai, L-S. and Chau, L-Y. Post-transcriptional regulation of H-ferritin mRNA:
Identification of a pyrimidine-rich sequence in 3'-untranslated region associated with
message stability in human monocytic THP-1 cells. J. Biol. Chem. 274: 30209-30214,
1999.
4. Lee, T-S. and Chau, L-Y. Fas/Fas ligand-mediated pathway is involved in oxidized
LDL-induced apoptosis in vascular smooth muscle cells. Am. J. Physiol.Cell Physiol.
280: C709-C718, 2001.
5. Juan, S-H., Lee, T-S., Tseng, K-W., Liou, J-Y., Shyue, S-K., Wu, K-K. and Chau, L-Y.
Adenovirus-mediated heme oxygenase-1 gene transfer inhibits the development of
atherosclerosis in apoE-deficient mice. Circulation 104, 1519-1525, 2001.
6. Lee, T-S. and Chau, L-Y. Heme oxygenase-1 mediates the anti-inflammatory effect of
interleukin-10 in mice. Nat. Med. 8, 240-246, 2002.
7. Chen, Y-H., Lin, S-J., Lin, M-W., Tsai, H-L., Kuo, S-S., Chen, J-W., Charng, M-J., Wu,
T-C., Chen, L-C., Ding, P.Y-A., Pan, W-H., Jou, Y-S., and Chau, L-Y. Microsatellite
polymorphism in promoter of heme oxygenase-1 gene is associated with susceptibility
to coronary artery disease in type 2 diabetic patients. Hum. Genet. 111:1-8; 2002
8. Lee, T-S., Tsai, H-L., and Chau, L-Y. Induction of heme oxygenase-1 expression in
muirne macrophages is essential for the anti-inflammatory effect of low dose 15-deoxy-
12,14-prostaglandin J2. J. Biol. Chem. 278:19325-19330; 2003. △
9. Chen, Y-H, Chau, L-Y, Lin, M-W, Chen, L-C, Yo, M-H, Chen, J-W, and Lin, S-J. Heme
oxygenase-1 gene promotor microsatellite polymorphism is associated with
angiographic restenosis after coronary stenting. Eur Heart J. 25:39-47; 2004.
10.Hu, C-M., Chen, Y-H., Chiang, M-T., and Chau, L-Y. Heme oxygenase-1 inhibits
9
angiotension II-induced cardiac hypertrophy in vitro and in vivo. Circulation accepted
pending revision; 2004.
10
Name in Chinese:陳志成
Name in English:Chen, Chih-Cheng
Education:University College London, UK
Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei
Title:Assistant Research Fellow, Institute of Biomedical Sciences, Academia Sinica
Tel:886-2-2652-3917, 886-2-2789-9057
Fax:886-2-2782-9224
My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/ccchen_c.html
E-mail:[email protected]
Fields of Specialty: Pain, Neurobiology, Gene Targeting, Mouse Genetics
Research Description:
Acid (protons) is one of the major factors in pain sensation. High concentrations of protons or tissue
acidosis occur in pain associated with inflammation, ischemia, tumors, etc. Therefore, the study of
genes involved in acid signaling will be beneficent to the development of new analgesic drugs.
We have cloned a few acid-sensing ion channels (ASICs) from sensory neurons and generated ASIC3
knockout and transgenic mice. From the study of ASIC3 knockout mice, we have confirmed that
ASIC3 is involved in pain sensation. In many nociceptive tests, we found that mice lack of the ion
channels showing hyperalgesic behaviors. This result was surprising but provided us a new insight of
role of protons, which may be involved in many different physiological functions. Thus, we will
continue screening and cloning the receptor genes for protons, as well as studying their roles in pain
sensation and other physiological functions by using transgenic and knockout mice models.
Specific projects include:
1. Transgenic & knockout mouse model of human familial disautonomia.
11
2. Pain behavior alteration of mice lack of proton-gated ion channel ASIC3
3. The roles of acid-sensing ion channels in sensory neurons.
4. Genetic mapping and molecular cloning of genes involved in acid-signaling
and nociception
Selected Recent Publication:
1. Chen, C.-C., Zimmer, A.M., Sun, W.H., Hall, J.E., Brownstein, M.J., and Zimmer, A.
(2002). A role for ASIC3 in the modulation of high-intensity pain stimuli. Proc. Natl.
Acad. Sci. USA 99, 8992-8997.
2. Akopian, A.N., Chen, C.-C., Ding, YN., Cesare, P., and Wood, J.N. (2000). A new
member of the acid-sensing ion channel family. Neuroreport 11, 2217-2222.
3. Akopian, A.N., Chen, C.-C., Souslova, V., Okuse, K., and Wood, J.N. (2000). Sensory
neuron-specific ion channels and receptors. In: Molecular Basis of Pain Induction, ed
Wood, J.N., Wiley-Liss Inc., pp.113-128
4. Chen, C.-C., England, S., Akopian, A.N., and Wood, J.N. (1998). A sensory neuron-
specific, proton-gated ion channel. Proc. Natl. Acad. Sci. USA 95, 10240-10245.
5. Krylova, O., Chen, C.-C., Akopian, A., Souslova, V., Okuse, K., Abson, N., Ravenal, S.,
and Wood, J.N. (1997). Ligand-gated ion channels of sensory neurons: from purines to
peppers. Biochemical Society Transactions 25, 842-844.
6. King, B., Chen, C.-C., Akopian, A.N., Burnstock, G., and Wood, J.N. (1997). A role for
calcineurin in the desensitisation of P2X3. Neuroreport 8, 1009-1102.
7. Chen, C.-C., Akopian, A.N., Sivilotti, L., Colquhoun, D., Burnstock, G., and Wood, J.N.
(1995). A P2X purinoceptor expressed by a subset of sensory neurons Nature 377, 428-
431.
8. Hsu, Y.L., Chen, C.-C., and Wu, J.L. (1995). Molecular relationships in infectious
pancreatic necrosis virus. Virus Research 37, 239-252.
12
Name in Chinese:張久瑗
Name in English:Chen, Joanne Jeou-Yuan
Education:University of Minnesota
Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei
Title:Associate Research Fellow, Institute of Biomedical Sciences, Academia Sinica
Tel:886-2-2652-3966, 886-2-2789-9046
Fax:886-2-2785-8594
My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/jychen_c.html
E-mail:[email protected]
Fields of Specialty:Cancer Genomics, Molecular and Tumor Biology
Research Description:
A major problem in the management of patients with cancer is the lack of specific tumor markers
for the early detection, the accurate prediction of the biological behavior and the accurate assessment
of prognosis. The identification of tumor-associated candidate genes provides an answer to this
problem. Gastric cancer (GC) is highly prevalent. To systematically dissect the pathways that are
involved in the initiation and progression of this disease, various approaches of representational
difference analysis (RDA) have been taken to isolate gastric cancer-associated genes. By genomic
RDA, chromosomal instability and microsatellite instability have been determined in GC at a genome-
wide level. A subset of GC was characteristic of high microsatellite instability as the result of
mutations in mismatch repair genes. In other GCs, distinct patterns of chromosomal instability and
DNA copy number changes are tightly associated with specific clinicopathologic features. Candidate
gene approach is underway to further explore he regions that may harbor candidate oncogenes or
tumor suppressor genes dominating the pathogenic development of specific subtypes of GC. By
13
various mRNA RDA, we have identified two thousands more genes that are differentially expressed in
GC. A gastric cancer gene chip based on the cDNA of these genes was established and microarray
hybridization was performed followed by cluster analyses to identify candidate genes associated with
the pathogenic development of GC of specific histopathologic subtypes and stages. Genes that are
involved in various pathways regulating cell proliferation or survival are focused and the potential
usage of them as molecular markers for GC patients is evaluated. By proteomics, we are using humoral
antibodies elicited in the sera of GC patients as reagents to isolate tumor antigens, with the hope to
identify overexpressed candidate genes that may play important roles in gastric tumorigenesis. The
goals of these studies are to provide a broad scope of the genetic events that are involved in the
pathogenic development of gastric adenocarcinoma, with the hope to establish better choices of useful
diagnostic and prognostic markers, and in the long run, to provide us the common denominator for
understanding, treating, and preventing this disease.
Selected Recent Publication:
1. Lo, P.-K., Chen, J.-Y., Tang, P.-P., Lin, J., Lin, C.-H., Su, L.-T., Wu, C.-H., Chen, T.-L.,
Yang, Y. and Wang, F.-F.* Identification of a mouse thiamine transporter gene as a
direct transcriptional target for p53. J. Biol. Chem. 276: 37186-37193, 2001.
2. Wu, C.-W., Chen, G.-D., Fann, C. S.-J., Lee, A. F.-Y., Chi, C.-W., Liu, J. M., Weier, U.
and Chen, J.-Y.* Clinical implications of chromosomal abnormalities in gastric
adenocarcinomas. Genes, Chromosomes and Cancer. 35:219-231, 2002.
3. Huang, C.-J. and Chen, J.-Y.* Identification of Additional IE2-p86-responsive Cis-
repressiive Sequences within the Human Cytomegalovirus Major Immediate Early
Promoter. J. Biomed. Sci. 9:460-470, 2002.
4. Fann, C. S.-J., Chen, J.-Y.*, Wu, C.-W., and Chi, C.-W. Regarding clinical implications
of chromosomal abnormalities in gastric adenocarcinomas. Genes, Chromosomes, and
Cancer 38:204-206, 2003.
5. Kao, C.-F., Chen, S.-Y., Chen, J.-Y., and Lee, Y.-H. W.* Modulation of p53
Transcription Regulatory Activity and Posttranslational Modification by Hepatitis C
Virus Core Protein. Oncogene (In press), 2004.
6. Liu, C.-A., Wang, M.-J., Chi, C.-W., Wu, C.-W., and Chen, J.-Y.* Overexpression of
Rho Effector Rhotekin Confers Increased Survival in Gastric Adenocarcinoma. J.
Biomed. Sci. (In press), 2004.
14
Name in Chinese:陳士隆
Name in English:Chen, Steve S.-L.
Education:Purdue University
Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei
Title:Research Fellow, Institute of Biomedical Sciences, Academia Sinica
Tel:886-2-2652-3933, 886-2-2789-9035
Fax:886-2-2785-8847
My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/slchen_c.html
E-mail:[email protected]
Fields of Specialty:Retrovirology, Virus-host Interactions, Viral Protein Functions, Viral
Pathogenesis
Research Description:
Our current research focuses on HIV-1 viral protein functions, viral protein-protein interactions
underlying viral pathogenesis, and on the development of genetic anti-HIV strategies. In the Gag
project, we recently demonstrated a novel mode of trans-dominant inhibition in HIV-1 replication by a
cytoplasmic domain fusion protein -gal/706-856. We aim to further understand the molecular, viral,
and cellular bases for the role of this inhibitor in modulation of Gag and Env expression. In the Env
project, we intend to examine the role of palmitoylation of the Env cytoplasmic domain in viral
replication and Env targeting to lipid rafts, and to understand the biological functions of the putative
cholesterol-binding motif located in the ectodomain of gp41. In a new SARS coronavirus project, we
intend to characterize the biological functions of the heptad repeat (HR)1, and HR2 motifs in the spike
protein in virus replication. In the gene transfer and therapy program, we attempt to understand
whether IL10, which was known to downregulate HIV-1 replication in vitro, can be used as a candidate
15
for designing a genetic, immunotherapeutic approach to controlling HIV-1 replication. Moreover, we
will examine whether expression of a cytoplasmic tail fragment and -gal/706-856 in lentiviral vector-
transduced human CD4+ T cells and primary cells can inhibit HIV-1 replication.
Selected Recent Publication:
1. Lee, S.-F., Wang, C.-T., Liang, J. Y.-P., Hong, S.-L., Huang, C.-C. and Chen, S. S.-L.
Multimerization potential of the cytoplasmic domain of the human immunodeficiency
virus type 1 transmembrane glycoprotein gp41. J. Biol. Chem. 275: 15809-15819, 2000.
2. Wang, C.-T., Chen, S. S.-L., and Chiang, C.-C. Assembly and release of human
immunodeficiency virus type 1 Gag proteins containing tandem repeats of the matrix
protein coding sequences in the matrix domain. Virology 278: 289-298, 2000.
3. Chiou, S.-H., Liu, J.-H., Hsu, W.-M., Chen, S. S.-L., Chang, S.-Y., Juan, L.-J., Lin, J.-
C., Yang, Y.-T., Wong, W.-W., Liu, C.-Y., Lin, Y.-S, Liu, W.-T., and Wu, C.-W.
Upregulation of Fas ligand expression by human cytomegalovirus immediate-early gene
2: a novel mechanism in CMV-induced apoptosis in human retina. J. Immnol. 167:
4098- 4103, 2001.
4. Chen, S. S.-L., Lee, S.-F., and Wang, C.-T. Cellular membrane-binding ability of the C-
terminal cytoplasmic domain of human immunodeficiency virus type 1 envelope
transmembrane protein gp41. J. Virol. 75: 9925-9938, 2001.
5. Lee, S.-F., Ko, C.-Y., Wang, C.-T., and Chen, S. S.-L. Effect of point mutations in the
N-terminus of the lentivirus lytic peptide-1 sequence of human immunodeficiency virus
type 1 transmembrane protein gp41 on Env stability. J. Biol. Chem. 277: 15363-15375,
2002.
6. Hsu, W.-M., Chen, S. .S.-L., Peng, C.-H., Chen, C.-F., Ko, Y.-C., Tsai, D.-C., Chou, C.-
K., Ho, L.-L., Chiou, S.-H., and Liu, J.-H. Elevated nitric oxide level in aqueous humor
of AIDS patients with cytomegalovirus retinitis. Ophthalmologica 217: 298-301, 2003.
7. Chen, S.-W., Chiu, H.-C., Liao, W.-H., Wang, F.-D., Chen, S. S.-L., and Wang, C.-T.
The virion-associated human immunodeficiency virus type 1 Gag-Pol carrying an active
protease domain in the matrix region is severely defective both in autoprocessing and in
trans processing of gag particles. Virology 318: 534-541, 2004.
8. Chan, W.-E., Wang, Y.-L., Lin, H.-H., and Chen, S. S.-L. Effect of extension of the
16
cytoplasmic domain of human immunodeficiency type 1 virus transmembrane protein
gp41 on virus replication. J. Virol. 78:5157-5159, 2004.
17
Name in Chinese:陳垣崇
Name in English:Chen, Yuan-Tsong
Education:Columbia University
Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei
Title:Distinguished Research Fellow/ Director, Institute of Biomedical Sciences, Academia Sinica
Tel:886-2-2652-3001, 886-2-2789-9104
Fax:886-2-2782-5573
My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/ytchen_c.htm
E-mail:[email protected]
Fields of Specialty:Human Genetics, Genomic Medicine
Research Description:
Our overall research interests are in translational research. We aim at translating the promise of
genomic medicine into clinical reality.
Specific projects at present time include:
1). Identification of novel genes/targets associated with human diseases. This includes
susceptibility genes for common multi-factorial diseases and pharmacogenetic disorders and disease
causing genes for single gene disorders. Genetic epidemiology, mouse ENU mutagenesis,
bioinformatics and proteomics are some approaches that we use in identification of novel genes
associated with the human disease. Genes for several monogenic diseases have been mapped and/or
identified. Genetic markers associated with drug-induced Stevens-Johnson syndrome have been
identified. A systematic, genome-wide, phenotype-driven mutagenesis program for gene function
studies in the mouse have resulted in the identification of a mouse model resembling human maple
syrup urine disease. We will continue our research along these lines to identify more novel disease
genes/ targets and to increase our understanding of the diseases.
18
2). Functional characterization of a novel glucose transporter and its role in diabetes mellitus. We
cloned a novel glucose transporter (Glu 10), which is highly expressed in pancreas and liver and is
located on a region of a chromosome where a diabetes mellitus type II locus has been mapped. We are
currently investigating its role in diabetes by generation of knock out mouse model and by direct
genetic association study of human patients affected with diabetes.
3). Enzyme and gene therapy and targeting mechanisms of Pompe disease. Pompe disease is a
fatal genetic muscle disorder. As enzyme replacement therapy for Pompe disease moves into clinical
trials the fundamental question of how the enzyme targets the heart and skeletal muscle remains
unanswered. In vitro studies have established that the uptake of the enzyme in cultured fibroblasts is
due to receptor-mediated endocytosis via the mannose-6-phosphate receptor (MPR300), however, it is
presently unclear if the same system is involved in vivo. We have generated tissue-specific MPR300
knockout mouse model to help us answer this question and to better define the role of the receptor in
vivo. In anticipation of expanding the clinical trial to adult and juvenile patients, we are also evaluating
what effects advanced age may have upon the efficacy of the enzyme and gene therapy using animal
models.
Selected Recent Publication:
1. Sun BD, Chen Y-T, Bird A, Amalfitano A, Koeberl DD. Long-term correction of
glycogen storage disease type II with a hybrid adenovirus-adeno-associated virus
vector. Mol Ther 7:193-201, 2003.
2. Wu JY, Kao HJ, Li SC, Stevens RD, Hillman S, Millington DS, and Chen YT. ENU
mutagenesis identifies mice with mitochondrial branched-chain aminotransferase
deficiency resembling human maple syrup urine disease. J Clin Invest, 113:434-440,
2004.
3. Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC, Wu JW, Chen YT. A
marker for Stevens-Johnson syndrome. Nature, 428:486 2004.
4. Quan H, Athirakul K, Westle, WC, Torres, GE, Stevens R, Chen YT, Coffman TM,
Caron MG. Hypertension and impaired glycine handling in mice lacking the orphan
transporter XT2. Molecular & Cellular Biology, 24: 4166-4173, 2004.
5. Hwu WL, Yang CF, Fann Cathy S J, Chen CL, Tsai TF, Chien YH, Chiang SC, Chen
CH, Hung SI , Wu JY, and Chen YT. Mapping of psoriasis to 17q terminus. J Medical
Genetics, in press, 2004.
19
6. Chen, Y.T. Glycogen storage diseases. In: Harrison Principles of Internal Medicine,
14th Edition, pp 2176-2182, 1998, 15th Edition, pp 2281-2289, 2001, 16th edition, in
press 2004.
20
Name in Chinese:陳儀莊
Name in English:Chern, Yijuang
Education:University of Massachusetts
Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei
Title:Research Fellow, Institute of Biomedical Sciences, Academia Sinica
Tel:886-2-2652-3913, 886-2-2789-9028
Fax:886-2-2782-9143
My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/ychern_c.html
E-mail:[email protected]
Fields of Specialty:Signal Transduction , Gene Regulation
Research Description:
We previously cloned the cDNA and the gene of the rat A2A adenosine receptor (A2A-R), which
contains seven transmembrane domains and belongs to the G protein-coupled receptor family.
Stimulation of A2A-R results in activation of adenylyl cyclase/protein kinase A (PKA) and protein
kinase C (PKC). One of A2A-R’s physiological functions is to protect cells against various assaults.
Using PC12 as a neuron-like model system, we demonstrated that atypical PKCs function downstream
of PKA to mediate the protective effect of the A2A-R against apoptosis evoked by serum withdrawal in
PC12 cells. In addition, A2A-R stimulation rescued the blockage of NGF-induced neurite outgrowth
when the NGF-evoked MAPK cascade was suppressed. In the central nervous system (CNS), the A2A-
R gene is heavily expressed in GABAergic striopallidal neurons, which selectively degenerate during
progression of Huntington’s disease (HD). We therefore are investigating the potential therapeutic
effects of A2A-R-selective agonists on HD using a transgenic mouse model (R6/2) of HD. Moreover,
we also are using cellular and transgenic approaches to study the gene regulation and function of A2A-R
21
in vivo. The principal objective of this research group is to understand the molecular mechanisms
underlying the physiological functions and the regulation of A2A-R.
Selected Recent Publication:
1. Liu, F.C., Wu, G.C., Hsieh, S.T., Lai, H.L., Wang, H.F., Wang, T.W. and Chern, Y.
Expression of type VI adenylyl cyclase in the central nervous system: implication for a
potential regulator of multiple signals in different neurotransmitter systems. FEBS Lett.
436: 92-98, 1998.
2. Lai, H.L., Lin, T.H., Kao, Y.Y., Lin, W.J., Hwang, M.J. and Chern, Y. The N terminal
domain of type VI adenylyl cyclase mediates its inhibition by protein kinase C. Mol.
Pharmacology 56: 644-650, 1999.
3. Lee, Y.C., Chang, C.W., Su, C.W., Lin, T.N., Sun, S.H., Lai, H.L. and Chern, Y. The 5'
untranslated regions of rat A2A adenosine receptor gene function as negative
translational regulators. J. Neurochem. 73: 1790-1798, 1999.
4. Chern, Y. Regulation of adenylyl cyclase in the central nervous system. Cellular
Signalling 12: 195-204, 2000.
5. Huang, N.K., Lin, Y.W., Huang, C.L., Messing, R.O. and Chern, Y. Activation of
protein kinase A and atypical protein kinase C by A2A adenosine receptors antagonizes
apoptosis due to serum deprivation in PC12 cells. J. Biol. Chem. 276: 13838-13846,
2001.
6. Wu, G.C., Lai, H.L., Lin, Y.W., Chu, Y.T. and Chern, Y. N-glycosylation and residues
Asn805 and Asn890 are involved in the functional properties of type VI adenylyl
cyclase. J. Biol. Chem. 276: 35450-35457, 2001.
7. Lin, T.H., Lai, H.L., Kao, Y.Y., Sun, C.N., Hwang, M.J. and Chern, Y. Protein kinase C
inhibits type VI adenylyl cyclase (ACVI) by phosphorylating the regulatory N domain
and two catalytic C1 and C2 domains. J. Biol. Chem. 277: 15721-15728, 2002.
8. Lee Y.-C., Chien C.-L., Sun C.-N., Chiang, M. C., Huang C.-L., Huang N.-K., Lai H.-
L., Lin Y.-S., Chiou S.-Y., Liao W.-L., Liu F.-C., Wang L., Tai M.-H., Lin T.-N. and
Chern Y. Characterization of the rat A2A adenosine receptor gene: a 4.8-kb promoter-
proximal DNA fragment confers selective expression in the central nervous system. Eur.
J. Neurosci. 18: 1786- 1796,2003.
9. Kao, Y.Y., Lai, H.L., Hwang, M.J. and Chern, Y. An important functional role of the N
22
terminus domain of type VI adenylyl cyclase (ACVI) in Gia-mediated inhibition. J.
Biol. Chem. (in press)
23
Name in Chinese:何美鄉
Name in English:Ho, Mei-Shang
Education: Indiana University
Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei
Title:Associate Research Fellow, Institute of Biomedical Sciences, Academia Sinica
Tel:886-2-2652-3045, 886-2-2789-9120
Fax:886-2-2782-3047
My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/ msho_c.html
E-mail:[email protected]
Fields of Specialty:Epidemiology ,Virology.
Research Description:.
Probing into the biological basis that renders the wide spectrum of clinical outcomes of microbial
infections represents one of the most intriguing aspects in clinical practice and research in infectious
diseases. It is generally contended that the interplay between hosts and micriobes contributes to the
main thrust in steering an infectious process towards a certain clinical outcome, i.e., the microbial
virulent or attenuated genes/factors vis-a- vis host掇 susceptible factors derived at the genetic level or
during the process of immunological response. The central themes in our laboratory are revolved
around queries into precisely the above question by studying two infection models: hepatitis B virus
(HBV) and enterovirus 71. For HBV investigation, our focus is on vaccine-related issues with
emphasis on vaccine failure and chronic HBV infection of vaccines. The ongoing projects include
study of genetic predisposition for chronic infection by the immune escape mutants and study of
human susceptible genes for HBV infection by genetic epidemiological approach. Enterovirus 71 - the
newly identified neurotropic enteroviruse, is epidemic prone in causing morbidity and mortality in
24
recent years. The ongoing projects include establishing animal models to distinguish strain differences
in virulence; studying the molecular basis for viral virulence by infectious clones derived from reverse
genetic technology, therefore, the host-virus interaction can be further studied by series of in vivo
experiments using mutant and chimera virus in conjunction with knock-out mice. Furthermore, we are
identifying the mammalian cellular receptors for enterovirus 71 which would provide basis for
establishment of a susceptible transgenic mice model for enterovirus 71 in vivo study.
Selected Recent Publication:
1. Ho, M.S., Mau, Y.C., Lu, C.F., Huang, S.F., Hsu, L.C., Lin, S.R. and Hsu, H.M. Patterns
of circulating hepatitis B surface antigen variants among vaccinated children born to
hepatitis B surface antigen carrier and non-carrier mothers. Journal of Biomedical
Science 5: 355-362, 1998.
2. Shih, S.R., Ho, M.S., Lin, K.H., Wu, S.L., Chen, Y.T., Wu, C.N., Lin, T.Y., Chang, L.Y.,
Tsao, K.C., Ning, H.C., Chang, P.Y., Jung, S.M., Hsueh, C. and Chang, K.S.Genetic
analysis of enterovirus 71 isolated from fatal and non-fatal cases of hand, foot and
mouth disease during an epidemic in Taiwan, 1998. Virus Research 68: 127-136, 2000.
3. Wu, C.N., Lin, Y.C., Fann, C., Liao, N.S., Shih, S.R. and Ho, M.S. Protection against
lethal enterovirus 71 infection in newborn mice by passive immunization with subunit
VP1 accines and inactivated virus. Vaccine 20: 895-400, 2002.
4. Lin, Y.C., Wu, C.N., Shih, S.R. and Ho, M.S. Characterization of a vero cell-adapted
virulent strain of enterovirus 71 suitable for use as a vaccine candidate. Vaccine 2002.
5. Ho, M.S., Chiu, L.Y., Lin, Y.C., Hu, C.Y., Lee, T.D., Fann, C.S.J., Tsai, J.F. and Chen,
D.S. Genetic predisposition to chronic hepatitis B infection in vaccinated children with
emphasis on immune escape variants. J. Med. Virology 2002.
6. Lin, Y.-C., Wu, C.-N., Shih, S.-R. and Ho, M.-S. Characterization of a vero cell-adapted
virulent strain of enterovirus 71 suitable for use as a vaccine candidate. Vaccine 20,
2485-2493, 2002.
7. Lin, T.-Y., Twu, S.-J., Ho, M.-S., Ch'ang, L.-Y. and Lee, C.-Y. Enterovirus 71 outbreak,
Taiwan: occurrence and recognition. J. Emerging Infectious Disease 9:291-293, 2003.
8. Shih, S.-R., Chiang, C., Chen, T.-C., Wu, C.-N., Hsu, J.-T., Lee, J.-C., Hwang, M.-J.,Li,
M.-L., Chen, G..-W. and Ho, M.-S. Mutations at KFRDI and VGK domains of
enterovirus 71 3C protease affect its RNA binding and proteolytic activities. J. Biomed.
25
Sci. 11(2):239-248, 2004.
26
Name in Chinese:李旭東
Name in English:Lee, Sho Tone
Education: University of Manitoba, Canada
Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei
Title:Research Fellow, Institute of Biomedical Sciences, Academia Sinica
Tel:886-2-2652-3935, 886-2-2789-9170
Fax:886-2-2785-8847
My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/stlee_c.html
E-mail:[email protected]
Fields of Specialty: Drug Resistance ,Vaccine Development
Research Description:
As a member of the Division of Infectious Diseases, our laboratory focuses our effort on two topics:
(1) study of the mechanism of genesis of drug resistance and gene amplification in protozoan
Leishmania parasites and the mechanism(s) of infection of Leishmania parasite to host mononuclear
phagocytes and (2) development of subunit and DNA vaccines against flavivirus.
In drug resistance: (i) a genome wide search of the genes activated during resistance induction in order
to understand the mechanisms of genesis behind drug resistance and gene amplification. Subtractive
hybridization and proteomic approaches are used for a genome wide comparison between the wildtype
and the drug-resistant Leishmania; (ii) an intercellular adhesive molecule (ICAM) cloned and
expressed is used to investigate the mechanism involved in the interaction between the parasite and its
host macrophage.
In the flaviral vaccine study, we focus on the development of subunit and DNA vaccines against
Japanese encephalitis virus (JEV) which is an important pathogen in Taiwan as well as in Eastern and
27
Southeastern Asia. A C-terminal fragment of JEV envelope (E) protein was found to induce protective
immunity against JEV. We are now mapping the smallest and most immunodominant fragment of this
antigen for inducing protective immunity against JEV using DNA priming-protein boosting strategies.
Selected Recent Publication:
1. Singh, A.K. and Lee, S.T. Status of respiration and ATP content in arsenite resistant
Leishmania mexicana amazonensis. Microbiol. Pathogen. 26(3): 171-174, 1999.
2. Lye, L.F., Chiang, S.C., Hsu, J.Y. and Lee, S.T. Expression and cellular localization of
ribonucleotide reductase small subunit M2 protein in hydroxyurea-resistant Leishmania
mexicana amazonensis Mol. Biochem. Parasitol. 102: 263-271, 1999.
3. Chiang, S.C., Ali, V., Haung, A.L., Chu K.U., and Lee, S.T. Molecular, cellular and
functional characterizations of a novel ICAM-like molecule of the Ig-superfamily from
L. m. amazonensis. Mol. Biochem. Parasitol. 112: 263-275, 2001.
4. Chia, S.C., Leung, P.S.C., Liao, C.P., Huang, J.H. and Lee, S.T. Fragment of Japanese
encephalitis virus envelope protein produced in Escherichia coli protects mice from
virus challenge. Microbial Pathogenesis 31(1): 9-19, 2001.
5. Chang, Y.H., Lee, S.T. and Lin, W.W. Effects of cannabionoids on LPS-stimulated
inflammatory mediator release from macrophages: involvement of Eicosanoids. J. Cell.
Biochem. 81: 715-723, 2001.
6. Chiang, S.C., Chang, S.C. and Lee, S.T. ICAM-L gene is conserved only in Leishmania
species in the family of kinetoplastida. Mol. Biochem. Parasitol. 124: 47-50, 2002.
7. Hsu, M.J., Lee, S.S., Lee, S.T. and Lin, W.W. Signaling mechanisms of
enhanced neutrophil phagocytosis and chemotaxis by the
polysaccharide purified from Ganoderma lucidum. Br. J. Pharmacol.
139(2): 289-98, 2003.
8. Chen, C.W., Lee, S.T., Wu, W.T., Fu W.M., Ho, F.M. and Lin, W.W. Signal
transduction for inhibition of inducible nitric oxide synthase and
cyclooxygenase-2 induction by capsaicin and related analogs in
macrophages. Br. J. Pharmacol. 140: 1077-1087, 2003.
9. Wu, H.W., Chen, C.T., Lin, Y.L. and Lee, S.T. Subfragments of the envelope gene are
highly protective against the Japanese encephalitis virus lethal infection in DNA
28
priming/protein boosting immunization strategies. Vaccine, 22: 793-800, 2004.
29
Name in Chinese:林天南
Name in English:Lin, Teng-Nan
Education:University of Missouri-Columbia
Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei
Title:Associate Research Fellow, Institute of Biomedical Sciences, Academia Sinica
Tel:886-2-2652-3396, 886-2-2789-9141
Fax:886-2-2785-8847
My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/tnlin_c.html
E-mail:[email protected]
Fields of Specialty:Cerebral Ischemia , Angiogenesis ,Neurochemistry
Research Description:
Brain injury as a result of cerebral vascular disease (stroke) is a major health problem in Taiwan.
Unfortunately, no treatment to limit brain damage is yet available. The need for intervention is great,
both because of the seriousness of the disorder and its prevalence.
The ultimate goal for us is to unravel the cellular and molecular mechanism of neuronal injury
and/or recovery following ischemia-reperfusion. Both in vivo “focal cerebral ischemia model
(MCAO)” and in vitro “primary neuronal and glial cultures” are using in our laboratory to explore
these questions. Both pharmacological and genetic approaches are using to facilitate our goal.
Research Interest:
1. Mechanism of Angiogenesis
2. Gene regulation of growth factors and their receptor
3. Cellular and molecular mechanism of neuronal injury and recovery
4. Gene transfer in CNS
Selected Recent Publication:30
1. Lin T-N, Wang PY, Chi SI, Kuo JS (1998) Differential regulation of ciliary neurotrophic
factor (CNTF) and CNTF receptor α(CNTFRα) expression following focal cerebral
ischemia. Mol Brain Res 55:71-80.
2. Cheung WM, Wang CK, Kuo JS, Lin T-N (1999) Changes in the level of glial fibrillary
acidic protein (GFAP) after mild and severe focal cerebral ischemia. Chinese J
Physiology 42(4):227-235.
3. Lin T-N, Wang CK, Cheung WM, Hsu CY (2000) Induction of angiopoietin and tie
receptor mRNA expression following cerebral ischemia-reperfusion. J. Cereb. Blood
Flow Metab. 20:387-395.
4. Cheung WM, Chen SF, Nian GM, Lin T-N (2000) Induction of angiogenesis related
genes in the contralateral cortex with a rat three-vessel occlusion model. Chinese J
Physiology 43(3):119-124.
5. Chi SI, Wang CK, Chen JJ, Chau LY, Lin T-N (2000) Differential regulation of H- and
L-ferritin mRNA subunits, ferritin protein and iron following focal cerebral ischemia-
reperfusion. Neuroscience 100(3):475-484.
6. Shih CL, Chi SI, Chiu TH, Sun GY, Lin T-N (2001) Ethanol Effects on Nitric Oxide
Production in Cerebral Pial Cultures. Alcoholism: Clin. Exp. Res. 25(4):612-618.
7. Lin T-N, Nian GM, Chen SF, Cheung WM, Chang C, Lin WC, Hsu CY (2001)
Induction of Tie-1 and Tie-2 protein expression after cerebral ischemia-reperfusion. J.
Cereb. Blood Flow Metab. 21(6):690-701.
8. Lin H, Lin T-N, Cheung WM, Nian GM, Tseng PH, Chen SF, Chen JJ, Shyue SK, Liou
JY, Wu CW, Wu KK (2002) Cyclooxygenase-1 (COX-1) and Bicistronic
COX-1/Prostacyclin synthase gene transfer protect against ischemic cerebral infarction.
Circulation 105:1962-1969 (r67-r74).
9. Lin T-N, Sun SW, Cheung WM, Li F, Chang C (2002) Dynamic changes in cerebral
blood flow and angiogenesis after transient focal cerebral ischemia in rats: evaluation
with serial MRI. Stroke 33:2985-2991.
10.Lin T-N, Kim GM, Chen JJ, Cheung WM, He YY, Hsu CY (2003) Differential
regulation of TSP-1 and TSP-2 following focal cerebral ischemia-reperfusion. Stroke
34:177-186.
31
Name in Chinese:林文昌
Name in English:Lin, Wen-Chang
Education:Case Western Reserve University
Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei
Title:Associate Research Fellow, Institute of Biomedical Sciences, Academia Sinica
Tel:886-2-2652-3967, 886-2-2789-9148
Fax:886-2-2785-8594
My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/ wclin_c.html
E-mail:[email protected]
Fields of Specialty:Bioinformatics, Tumor Biology, Cancer Metastasis
Research Description:
The long-term research goal of our laboratory is to utilize bioinformatic tools/databases in elucidating
molecular and cellular aspects of tumor progression and host-tumor immune responses. Our research
efforts are intended to improve treatment strategies of human cancer patients. Current major projects
involve:
1. Examination of protein tyrosine-kinase and tyrosine-phosphatase expression profiles in human
gastric cancer tissues. By using degenerated PCR primers according to the consensus catalytic domain
motifs, we could amplify kinase/phosphatase molecules from cancer tissues. We have identified more
than 50 different protein kinases as well as 20 different new protein kinase genes. We have
demonstrated that expression of tie-1 and mkk4 kinases correlates with prognostic outcomes of gastric
cancer patients. RAGE based bioinformatic tools are now in development to improve their applications
in clinical studies. Bioinformatic is emerging as a new research field and becoming an important
research tool. We have created a novel comparative-gene-identification (CGI) approach by applying
32
comparative proteomics in human dbEST data-mining efforts. With the CGI tool and human dbEST,
we have discovered over 500,000 cSNP and a new wobble splicing mechanism in human gene
transcripts. Our present goal is to integrate protein functional motif discovery and bioinformatic
databases by building bioinformatic data-mining tools.
Selected Recent Publication:
1. Hsiao-Wei Kao, Huan-Chen Chen , Hsing-Jien Kung, and Wen-chang Lin. 2003.
Tyrosine-Kinase Expression Profiles in Human Gastric Cancer Cell Lines and Their
Modulations with Retinoic Acids. British Journal of Cancer. 88: 1058-1064.
2. Chew-Wun Wu, Anna F.-Y. Li, Chin-Wen Chi, Cheng-Jien Huang, Chen Lung Huang,
Wing-Yiu Liu, and Wen-chang Lin. 2003. Arg Tyrosine Kinase Expression in Human
Gastric Adenocarcinoma is Associated with Vessel Invasion. Anticancer Res. 23: 205-
210.
3. Trees-Juen Chuang, Wen-Chang Lin, Hurng-Chun Lee, Chi-Wei Wang, Keh-Lin Hsiao,
Zi-Hao Wang, Danny Shieh, Simon C. Lin, and Lan-Yang Ch'ang. 2003. A Complexity
Reduction Algorithm for Analysis and Annotation of Large Genomic Sequences.
Genome Research. 13: 313-322.
4. Wen-chang Lin. 2002. Protein Tyrosine Kinase and Phosphatase Expression Profiling in
Human Cancers. In Methods in Molecular Medicine, Vol. 218: Cancer Cell Signaling:
Methods and Protocols (David M. Terrian, ed.), Humana Press, Inc., Totowa, N.J. pp.
113-125.
5. Chew-Wun Wu, Anna F.-Y. Li, Chin-Wen Chi, Chun-Hung Lai, Chen Lung Huang, Su-
Shun Lo, Wing-Yiu Liu, Wen-chang Lin. 2002. Clinical Significance of Axl Kinase
Family in Gastric Cancer. Anticancer Res. 22: 1071-1078.
6. Chew-Wun Wu, Chin-Wen Chi, and Wen-chang Lin. 2002. Gastric Cancer: Prognostic
and Diagnostic Advances. Expert Reviews in Molecular Medicine. 21 March, "
http://www-ermm.cbcu.cam.ac.uk/02004337h.htm ".
7. Chun-Hung Lai, Jian-Yuan Chiu, and Wen-chang Lin. 2001. Identification of the
Human crooked neck gene by Comparative Gene Identification. Biochimica et
Biophysica Acta. 1517: 449-454.
8. Wen-chang Lin, Hsiao-Wei Kao, Daniel Robbinson, Hsing-Jien Kung, Chew-Wun Wu,
and Hua-Chien Chen. 2000. Tyrosine Kinases and Gastric Cancer. Oncogene. 19: 5680-
33
5689.
9. Chun-Huang Lai, Chang-Yuan Chou, Lan-Yang Ch'ang, Chung-Shyan Liu, Wen-chang
Lin. 2000. Identification of Novel Human Genes Evolutionarily Conserved in C.
elegans by Comparative Proteomics. Genome Res. 10: 703-713.
34
Name in Chinese:潘文涵
Name in English:Pan, Wen-Harn
Education:Cornell University
Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei
Title:Research Fellow, Institute of Biomedical Sciences, Academia Sinica
Tel:886-2-2652-3042, 886-2-2789-9121
Fax:886-2-2782-3047
My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/whpan_c.html
E-mail:[email protected]
Fields of Specialty: Cardiovascular, Nutrition, Genetic Epidemiology
Research Description:
Our research mainly focuses on mRNA processing and transport in eukaryotic cells.
The splicing of precursor mRNA is a key step of gene expression. In higher eukaryotes,
alternative splicing of pre-mRNAs greatly increases the complexity of the genome8. We have been
interested in the molecular mechanisms by which alternative splicing is controlled. Serine/arginine-rich
splicing factors (SR proteins) play important roles in both constitutive and regulated splicing. Dynamic
localization of splicing regulatory factors provides a means by which splicing can be regulated. We
therefore investigate the nucleocytoplasmic transport of SR proteins. We have identified an importin-
beta family member, termed transportin-SR, and found that it is responsible for nuclear import of
phosphorylated SR proteins3, 4. We have also examined the roles of SR proteins in post-splicing mRNA
maturation events9. We are interested in how cellular signaling controls phosphorylation of SR
proteins. We recently found that an SR protein becomes hyperphosphorylated upon inhibition of
mRNA synthesis and that this SR protein is destabilized when hyperphosphorylated6. In addition, we
35
identified a novel splicing regulatory protein, RBM4, that antagonizes the activity of SR proteins in
splice site and exon selection5. We also explore the molecular mechanisms of how transcription factors
control splicing regulation2 and orchestrate the assembly of the spliceosome10.
RNA export is also a key step of gene expression. We recently found that SR-like protein
Pnn/DRS becomes associated with the spliced mature mRNA during the splicing process. Our study
indicates that Pnn functions as a platform for the assembly of splicing and/or export complexes in the
nucleus7. At present, we continue to study whether phosphorylation of export factors has any effect on
mRNA export.
Selected Recent Publication:
1. Chang, H.Y., Suchindran, C.M. and Pan, W.H. Using the overdispersed exponential
family to estimate the distribution of usual daily intakes of people aged between 18 and
28 in Taiwan. Statistics in Medicine 20(15): 2337-2350, 2001.
2. Chang, H.Y., Pan, W.H., Yeh, W.T. and Tsai, K.S. Hyperuricemia and gout in Taiwan:
results from the Nutritional and Health Survey in Taiwan (NAHSIT: 1993-96). Journal
of Rheumatology 28(7): 1640-1646, 2001.
3. Pan, W.H., Chang, H.Y., Yeh, W.T., Hsiao, S.Y. and Hung, Y.T. Prevalence, awareness,
treatment and control of hypertension in Taiwan: results of nutrition and health survey
in Taiwan (NAHSIT) 1993-1996. Journal Human Hypertension 15(11): 793-798, 2001.
4. Yeh, C.J., Pan, W.H., Jong, Y.S., Kuo, Y.Y. and Lo, C.H. Incidence and predictors of
isolated systolic hypertension and isolated diastolic hypertension in Taiwan. Journal
Formos Med Assoc. 100(10): 668-75, 2001.
5. Wu, S.Y., Fann, C.S.J., Chen, J.W., Jou, Y.S. and Pan, W.H. Association between
markers in chromosomal region 17q23 and young-onset hypertension: A TDT study.
Journal of Medical Genetics 39: 42-44, 2002.
6. Pan W.H., Yeh W.T., Chang H.Y., Hwu C.M., Ho L.T.. Prevalence and awareness of
diabetes and mean fasting glucose by age, sex, and region: results from the Nutrition
and Health Survey in Taiwan, 1993-1996. Diabet Med. 20(3):182-5, 2003.
7. Kang M.J., Lin Y.C., Yeh W.H., Pan W.H. Vitamin E status and its dietary determinants
in Taiwanese: Results of the Nutrition and Health Survey in Taiwan 1993-1996. Eur J
Nutr. 43(2): 86-92, 2004.
8. Pan W.H., Flegal K.M., Chang H.Y., Yeh W.T., Yeh C.J., Lee W.C. Body mass index
36
and obesity-related metabolic disorders in Taiwanese and US whites and blacks:
implications for definitions of overweight and obesity for Asians. Am. J. of Clinical
Nutrition 79: 31-39, 2004.
37
Name in Chinese:羅傅倫
Name in English:Roffler, Steve R.
Education: University of California, Berkeley
Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei
Title:Research Fellow, Institute of Biomedical Sciences, Academia Sinica
Tel:886-2-2652-3079 886-2-2789-9152
Fax:886-2-2782-9142
My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/roffler_c.html
E-mail:[email protected]
Fields of Specialty:Monoclonal Antibodies, Prodrugs, Surface Expression, Directed Molecular
Evolution
Research Description:
We have synthesized glucuronide prodrugs that can be preferentially activated at tumor cells by
antibody-enzyme conjugates (immunoenzymes). Current studies are focused on improving the utility
of recombinant immunoenzymes by directed molecular evolution and translation of prodrug therapy to
the clinic. We are also investigating the efficacy and mode of action of a new glucuronide prodrug of
9-aminocamptothecin that displays good antitumor activity without immunoenzyme pretargeting.
Another area of interest is the development of novel gene-therapy strategies based on the
expression of chimeric proteins on the surface of mammalian cells. We are focusing on the expression
of enzymes for prodrug activation and single-chain antibodies for specific regulation of lymphocytes.
We are interested in understanding how different domains of chimeric proteins affect their transport
and retention on the cell surface.
We have also developed monoclonal antibodies that identify proteins that are involved in the
38
migration, adhesion and invasion of lung adenocarcinoma cells as well as in the regulation of
endothelial cell angiogenesis. Current studies are focused on investigation of protein-protein
interactions and signal transduction pathways involved in cancer cell metastasis and angiogenesis.
Selected Recent Publication:
1. NM Tsai, TL Cheng and SR Roffler. Sensitive quantitation of poly(ethylene glycol)-
modified proteins. Biotechniques 30: 396-402, 2001.
2. BM Chen, TL Cheng, SC Tzou and SR Roffler. Potentiation of antitumor immunity by
antibody-directed enzyme prodrug therapy. Int. J. Cancer, 94: 850-858, 2001.
3. JW Chen, K Peck, TM Hong, SC Yang, YP Sher, JY Shih, R Wu, JL Cheng, SR Roffler,
CW Wu and PC Yang. Global Analysis of Gene Expression in Invasion by a Lung
Cancer Model. Cancer Res., 61: 5223-5230, 2001.
4. KW Liao, WC Chou, YC Lo and SR Roffler. Design of transgenes for efficient
expression of active chimeric proteins on mammalian cells. Biotechnol Bioeng, 73:313-
323, 2001.
5. ZM Prijovich, BM Chen, YL Leu, JW Chern and SR Roffler. Antitumor activity and
toxicity of the new glucuronide prodrug 9-aminocamptothecin glucuronide (9ACG) in
mice. Br. J. Cancer, 86: 1634-1638, 2002.
6. KM Bernt, DS Steinwaerder, S Ni, ZY Li, SR Roffler and A Lieber. Enzyme-activated
prodrug therapy enhances tumor-specific replication of adenovirus vectors. Cancer Res.,
62: 6089-98, 2002.
7. YR Kao, JY Shih, WC Wen, YP Ko, BM Chen, YL Chan, YW Chu, PC Yang, CW Wu
and SR Roffler. Tumor-associated antigen L6 (TAL6) and the invasion of human lung
cancer cells. Clin. Cancer Res., 9: 2807-2816, 2003.
8. KW Liao, BM Chen, TB Liu, SC Tzo, YM Lin, KF Lin, CI Su and SR Roffler. Stable
expression of chimeric anti-CD3 receptors on mammalian cells for stimulation of anti-
tumor immunity. Cancer Gene Therapy. 10: 779-790, 2003.
9. CH Lo, SC Lee, PY Wu, WY Pan, J Su, CW Cheng, SR Roffler, BL Chiang, CN Lee,
CW Wu and MH Tao. Antitumor and antimetastatic activity of IL-23. J. Immunol. 171:
600-607, 2003.
10.ZM Prijovich, YL Leu and SR Roffler. Stability of the new prodrug 9-
aminocamptothecin glucuronide (9ACG) in the presence of human serum albumin.
39
Biochem. Pharmacol., 66: 1181-1187, 2003.
40
Name in Chinese:謝如姬
Name in English:Shieh, Ru-Chi
Education:University of Rochester
Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei
Title:Associate Research Fellow, Institute of Biomedical Sciences, Academia Sinica
Tel:886-2-2652-3914, 886-2-2789-9024
Fax:886-2-2782-9143
My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/ruchi_c.html
E-mail:[email protected]
Fields of Specialty:Electrophysiology, Biophysics, Fluorescence
Research Description:
Inward rectifier K+ channels (Kir) are important in maintaining stable resting membrane potentials and
controlling excitability of many cells. These channels are also involved in other physiological
processes such as vascular tone, heart rate, renal salt flow, and insulin release. The focus of our
laboratory is on the ion permeating and gating processes in Kir2.1 channels. Recently, we have
combined electrophysiology, site-directed mutangensis, and chemical modification to probe the
conformational changes in Kir2.1 channels during membrane voltage-induced inactivation. Using this
combination of techniques, we are currently studying the ion-ion interaction involved in ion
permeation through the Kir2.1 channel. These experiments may shed light on the voltage-dependent
gating processes of Kir2.1 channels and provide further insights into the interaction of permeant ions
and blockers with the Kir2.1 channels.
41
Selected Recent Publication:
1. R-C Shieh. Mechanisms underlying the time-dependent decay of inward currents
through cloned Kir2.1 channels expressed in Xenopus oocytes. J Physiol (Lond),
526.2:241-252, 2000.
2. R-C Shieh and Y-L Lee. Ammonium ions induce inactivation of Kir2.1 channels
expressed in Xenopus oocytes. J Physiol (Lond), 535.2:359-370, 2001.
3. Wang, I., Wu, S.H., Chang, H.K., Shieh, R-C, Yu, H.M. and Chen, C. Solution structure
of a K+-channel blocker from the scorpion toxin of Tityus cambridgei. Protein Science
11: 390-400, 2002.
4. H-KChang and R-C Shieh. Conformational Changes in Kir2.1 Channels during NH4+-
Induced Inactivation. J Biol Chem 278 (2): 908-918, 2003.
5. H-K Chang, S-H Yeh, R-C Shieh. The effects of spermine on the accessibility of
residues in the M2 segment of Kir2.1 channels expressed in Xenopus oocytes.J Physiol,
553(1):101-12, 2003.
42
Name in Chinese:謝小燕
Name in English:Shieh, Sheau-Yann
Education:Baylor College of Medicine
Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei
Title:Assistant Research Fellow, Institute of Biomedical Sciences, Academia Sinica
Tel:886-2-2652-3916, 886-2-2789-9056
Fax:886-2-2782-9143
My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/ssy_c.html
E-mail:[email protected]
Fields of Specialty:Cancer Research, Molecular Biology, Biochemistry
Research Description:
The tumor suppressor protein p53 play an important role in maintaining genome stability. The
significance is fully illustrated by its high frequency (over 50%) of deletion or mutation in tumors.
Under normal condition, the cellular p53 protein is unstable and barely detectable. However, upon
genotoxic stress such as ionizing radiation, UV, hypoxia, or even nutrient depletion, p53 is stabilized
and activated, which then leads to either G1/G2 growth arrest or programmed cell death (apoptosis).
Our main interest is to decipher the signal transduction pathways and the molecular mechanisms
underlying p53 induction.
DNA damage-induced p53 phosphorylation
The possibility that phosphorylation may play a role in the signaling to p53 has been a subject of
intense investigation. In fact, we and others have discovered that DNA damage induces p53
phosphorylation at multiple sites in the N-terminus and the C-terminus of the protein. However, the
connection between these phosphorylation events and p53 induction remains to be established. We
43
have recently identified two cell cycle checkpoint kinases, hCHK1 and CHK2, as p53 kinases that
phosphorylate DNA damage-inducible sites in vitro. The possibility that other cell cycle checkpoint
players may also participate in the signal transduction process upstream of CHKs is now under
investigation. We are also interested in identifying additional p53 kinases and their interacting
proteins, as well as their effects on p53.
Molecular mechanism underlying p53 stabilization
Several proteins have been shown to regulate the half-life of p53 either directly or indirectly. One of
them, the oncoprotein MDM2, binds the N-terminus of p53, and as a result, inhibits transcription
activation by p53 and promotes p53 degredation through ubiquitin / proteasome pathway. Although
p53 N-terminal phosphorylation can modulate MDM2-p53 interaction, some stress-related
stabilization of p53 does not appear to involve phosphorylation. Other lines of evidence also suggest
that different genotoxic agents may signal to p53 through different pathways. We are interested in
locating the responsible p53 domain(s) that can mediate these stabilizing effects, as well as potential
proteins that interact with these domains.
Selected Recent Publication:
1. Tibbetts, R.S., Brumbaugh, K.M., Williams, J.M., Sarkaria, J.N., Cliby, W.A., Shieh,
S.Y., Taya, Y., Prives, C. and Abraham, R.T. A role for ATR in the DNA damage-
induced phosphorylation of p53. Genes & Dev. 13: 152-157, 1999.
2. Shieh, S.Y., Taya, Y. and Prives, C. DNA damage-inducible phosphorylation of p53 at
N-terminal sites including a novel site, serine 20, requires tetramerization. EMBO J. 18:
1815-1823, 1999.
3. Shieh, S.Y., Ahn, J., Tamai, K., Taya, Y. and Prives, C. The human homologues of
checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage
inducible sites. Genes & Dev. 14: 289-300[user1], 2000.
4. Gottifredi, V., Shieh, S. -Y. and Prives, C. Regulation of p53 after different forms of
stress and at different cell cycle stage. Cold Spring Harbor Symp. Quant. Biol. LXV:
483-487, 2000.
5. Gottifredi, V., Karni-Schmidt, O., Shieh, S.-Y. and Prives, C. p53 down-regulates CHK1
through p21 and the retinoblastoma protein. Mol. Cell. Biol. 21: 1066-1076, 2001.
6. Gottifredi, V., Shieh, S.Y., Taya, Y. and Prives, C. p53 accumulates but is functionally
impaired when DNA synthesis is blocked. Proc. Natl. Acad. Sci. USA 98: 1036-1041,
44
2001.
45
Name in Chinese:徐松錕
Name in English:Shyue, Song-Kun
Education:Universityn of Texas-Houston
Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei
Title:Assistant Research Fellow, Institute of Biomedical Sciences, Academia Sinica
Tel:886-2-2652-3962, 886-2-2789-9153
Fax:886-2-2785-8847
My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/skshyue_c.html
E-mail:[email protected]
Fields of Specialty: Viral Vector Gene Transfer, Cardiovascular Diseases
Research Description:
We have been working with adenovirus (Ad) mediated gene transfer and therapy to study
cardiovascular related diseases and molecular mechanism. Ad is one of the most efficient delivering
vectors for in vivo and in vitro gene transfer. First and E2b deleted second generation Ad systems have
been established in our laboratory. We have constructed many recombinant Ads related to antioxidants,
vasoprotection and immune response. We are currently focusing on the following projects:
1. Modifying Ad delivery system by: 1) Cells and protocol modification to improve viral
packaging and production efficiency to save time and cost. 2) To improve and develop
2nd and 3rd generation Ad in their construct and production for long term gene therapy.
2. Investigating the protection and therapeutic effects as well as their molecular
mechanisms of vasoprotective molecules in cardiovascular diseases, including
atherosclerosis and pulmonary hypertension.
3. Gene regulation and its mechanism of caveolin-1 in cancer cells.
46
4. Using microarray and proteomic tools to study the constitutional types in Traditional
Chinese Medicine, such as hot and cold, to unveil their related genes and proteins, and to
investigate the molecular mechanism of Traditional Chinese Medicine.
Selected Recent Publication:
1. Li, W. H., Boissinot, S., Tan, Y., Shyue, S.K. and Hewett-Emmett, D. Evolutionary
genetics of primate color vision. Evolutionary Biology 32: 151-178, 2000.
2. Shyue, S.K., Tsai, M.J., Liou, J.Y., Willerson, J.T. and Wu, K.K. Selective augmentation
of prostacyclin production by combined prostacyclin synthase and cyclooxygenase-1
gene transfer. Circulation 103:2090-2095, 2001.
3. Liou, J.Y., Deng, W.G., Gilroy, D.K., Shyue, S.K. and Wu, K.K. Colocalization and
interaction of cyclooxygenase-2 with caveolin-1 in human fibroblasts. J. Biol. Chem.
276: 34975-82, 2001.
4. Juan, S.H., Lee, T.S., Tseng, K.W., Liou, J.Y., Shyue, S.K., Wu, K.K. and Chau, L.Y.
Adenovirus-mediated heme oxygenase-1 gene transfer inhibits the development of
atherosclerosis in apoE-deficient mice. Circulation 104: 1519-25, 2001.
5. Lin H, Lin TN, Cheung WM, Nian GM, Tseng PH, Chen SF, Chen JJ, Shyue SK, Liou
JY, Wu CW, Wu KK. Cyclooxygenase-1 and bicistronic cyclooxygenase-1/prostacyclin
synthase gene transfer protect against ischemic cerebral infarction. Circulation Apr
23;105(16):1962-9, 2002.
6. Yu, N, Chen, FC, Ota, S, Jorde, LB, Pamilo, P, Patthy, L, Ramsay, M, Jenkins, T, Shyue,
SK, Li, WH. Larger genetic differences within africans than between africans and
eurasians. Genetics 161(1):269-74, 2002.
7. Huang CL, Huang NK, Shyue SK, Chern Y. Hydrogen peroxide induces loss of
dopamine transporter activity: a calcium-dependent oxidative mechanism. J
Neurochem. 86(5):1247-59, 2003.
8. 游恆懿、徐松錕、陳光偉 以基因晶片分析經附子乾薑培養的腎細胞基因表達。中西
整合醫學雜誌 4(1):1-6, 2003.
9. Lin SJ, Shyue SK, Liu PL, Chen YH, Ku HH, Chen JW, Tam KB and Chen YL
Adenovirus-mediated overexpression of catalase attenuates oxLDL-induced apoptosis
in human aortic endothelial cells via AP-1 and C-Jun N-terminal kinase/extracellular
signal-regulated kinase mitogen-activated protein kinase pathways. J. Mol. Cell.
47
Cardiol. 36(1):129-39, 2004.
48
Name in Chinese:唐堂
Name in English:Tang, Tang k..
Education:Yale University
Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei
Title:Research Fellow, Institute of Biomedical Sciences, Academia Sinica
Tel:886-2-2652-3901, 886-2-2789-9156
Fax:886-2-2782-9143
My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/ttang_c.html
E-mail:[email protected]
Fields of Specialty:Cell and Developmental Biology, Cell Mitosis and Germ Cell Development
Research Description:
A). Cell Cycle Control and Cancer Genetic Instability
Genetic instability is a common characteristic of many human cancers. Although, little is known
about the mechanisms that generate genetic abnormality, missegregation of chromosomes through the
assembly of dysfunctional mitotic spindles may play essential roles. The centrosome functions as the
major microtubule organizing center of the cells. During cell mitosis, the centrosome organizes the
microtubule array of the mitotic spindle and thereby makes possible equal segregation of sister
chromatids into two daughter cells. Many reports have shown that defects in centrosome function lead
to aneuploid and genetic instability in cancer cells. We previously identified several centrosomal
proteins including aurora-A, CPAP, protein 4.1 and NuMA. In this project, we propose to
systematically and qualitatively analyze the protein composition of centrosome by proteomic
approach, particularly focusing on the identification of novel centrosomal kinases and their substrates.
Furthermore, we will examine the possible roles of these newly identified proteins involved in cell
49
mitosis and genomic instability.
B). Gene Regulation and Germ Cell Development
Spermatogenesis in mammals is a complex system that leads to the formation of male gametes.
During spermatogenesis, male germ cells undergo major morphological and biochemical changes,
which are regulated by the stage-specific transcriptional and translational activation of numerous genes
and protein kinases. We previously identified a novel serine/threonine kinase, Aie1 (aurora-C) and its
gene regulator Tzfp (testis zinc finger protein). Both Aie1 and Tzfp are expressed in testis and
particularly in meiotic pachytene spermatocytes, suggesting a possible role of these two proteins
involved in spermatogenesis. Recently, we demonstrate that Tzfp binds to the promoter region of Aie1
gene through its carboxyl zinc finger domain, which suggests that the expression of Aie1 gene may be
regulated by Tzfp. We currently produced Tzfp knockout mice. The possible roles of these two
proteins are currently under investigation. The results from these studies should explore the unrevealed
signaling pathways and regulation in germ cell development in the future.
Selected Recent Publication:
1. Hung, L-Y., Tang, C-J. C., Tang, T.K. (2000). P4.1R (135 kDa) interacts with a novel
centrosomal protein (CPAP), which is associated with the -tubulin complex. Mol. Cell.
Biol. 20, 7813-7825.
2. Tang, C-J.C., Chuang, C-K., Hu, H-M., and Tang, T.K. (2001) The zinc finger domain of
Tzfp binds to the tbs motif located at the upstream flanking region of the Aie1 (aurora-C)
kinase gene. J. Biol. Chem. 276, 19631-19639.
3. Chen, S-H., and Tang T.K. (2002) Mutational analysis of the phosphorylation sites of the
Aie1(aurora-C) kinase in vitro. DNA Cell Biol. 21, 41-46.
4. Peng, B., Sutherland, K.D., Sum, E.Y.M., Olayioye, M., Wittlin, S., Tang, T.K.,
Lindeman, G.J., and Visvader, J.E. (2002) CPAP is novel Stat5-interacting cofactor that
augments Stat5-mediated transcriptional activity. Mol. Endocrinol. 16, 2019-2033.
5. Hung, L-Y., Chang, C-W., and Tang, T. K. (2003) Methods and compositions for
destabilizing microtubules. USA Patent-pending application
6. Tang, C-J. C., Hu, H-M, and Tang, T. K. (2004) NuMA (Nuclear Mitotic Apparatus
Protein) expression and function in mouse oocyte and early embryo. J. Biomed. Sci. (in
press).
7. Hung, L-Y., Chen, H-L., Chang, C-W., Li, B-R., and Tang, T. K. (2004) Identification of
50
a novel microtubule-destabilizing motif in CPAP that binds to tubulin heterodimers and
inhibits microtubule assembly. Mol. Biol. Cell. (in press)
51
Name in Chinese:陶秘華
Name in English:Tao, Mi-Hua
Education: Columbia University
Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei
Title:Research Fellow, Institute of Biomedical Sciences, Academia Sinica
Tel:886-2-2652-3078, 886-2-2789-9151
Fax:886-2-2782-9142
My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/ tao_c.html
E-mail:[email protected]
Fields of Specialty:Infectious Disease, Immunology, Vaccines, Tumor immunology, Hepatitis B
virus immunology
Research Description:
The major interest of our laboratory is to develop novel immunotherapeutic methods for treating
cancers and chronic hepatitis B virus infection. We focus on applying cytokines and immune
costimulatory molecules to modulate immune responses for enhancing the therapeutic effects. The
state of the art technologies, such as DNA vaccines, dendritic cell vaccines, in vivo electroporation, and
engineered antibodies are used in these studies. Details of our current research projects can be found at
the web site www.ibms.sinica.edu.tw/%7Ebmtao/. Following are brief summaries of some of our
research activities:
1. Cancer Immunotherapy and Gene Therapy
We have generated immunocytokines that can target cytokines to the tumor site to enhance their
tumoricidal effects. Application of immunocytokines is one of the most promising approaches
developed recently for cancer immunotherapy. Cytokines and other costimulatory molecules are
52
also applied to engineer tumor antigens to generate more potent cancer vaccines.
2.Therapeutic Vaccines for Treatment of Chronic Hepatitis B Virus Infection
We have previously demonstrated that plasmid DNA encoding HBsAg induced humoral and cellular
immune responses. We also demonstrated that the magnitude and nature of the immune responses
induced by HBsAg DNA vaccine could be modulated by coexpression of cytokine plasmids. Based
on these results, we are now developing therapeutic vaccines against chronic HBV infections using
several novel approaches including DNA vaccines, dendritic-cell-based vaccines, and adenovirus
producing cytokines/costimulatory molecules. A number of HBV transgenic mouse strains have
been generated as animal models for HBV chronic infection.
Selected Recent Publication:
1. Huang, T.H., Wu, P.Y., Lee, C.N., Huang, H.I., Hsieh, S.L., Kung, J. and Tao, M.H.
Enhanced antitumor immunity by fusion of CTLA-4 to a self tumor antigen. Blood
(Plenary paper) 96: 3663-3670, 2000.
2. Chen, H.W., Pan, C.H., Huang, H.W., Liau, M.Y., Chiang, J.R. and Tao, M.H..
Suppression of immune response and protective immunity to a Japanese encephalitis
virus DNA vaccine by coadministration of an IL-12-expressing plasmid. J. Immunol.
166: 7419-7426, 2001.
3. Pan, C.H., Chen, H.W., Huang, H.W. and Tao, M.H.. Protective mechanisms induced by
a Japanese encephalitis virus DNA vaccine: requirement for antibody but not CD8+
cytotoxic T cell responses. J. Virol. 75: 11457-11463, 2001
4. Lee, S.C., Wu, C.J., Wu, P.Y., Huang, Y.L., Wu, C.W. and Tao, M.H. Inhibition of
estabhished subcutaneous and metastatic murine tumors by intramuscular
electroporation of the Interleukin 12 gene. J. Biomed. Sci. 10: 73-86, 2003
5. Lo, C.H., Lee, S.C., Wu, P.Y., Pan, W.Y., Su, J., Cheng, C.W., Roffler, S.R., Chiang,
B.L., Lee, C.N., Wu, C.W. and Tao, M.H. Antitumor and antimetastatic activity of
Interleukin 23. J. Immunol. 171: 600-607, 2003
6. Wu, C.J., Huang, H.W. and Tao, M.H. Induction of cross-protection against two wild-
type Taiwanese isolates of Japanese encephalitis virus using Beijing-1 strain DNA
vaccine. Vaccine 21: 3938-3945, 2003
7. Huang, H.I., Wu, P.Y., Teo, C.Y., Chen, M.N., Chen, Y.C. and Tao, M.H. Idiotype-CD40
ligand fusion protein induces protective immunity against B-cell lymphoma. Int. J.
53
Cancer 108: 696-703, 2004.
54
Name in Chinese:譚婉玉
Name in English:Tarn, Woan-Yuh
Education:National Tsing Hua University
Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei
Title:Associate Research Fellow, Institute of Biomedical Sciences, Academia Sinica
Tel:886-2-2652-3052, 886-2-2789-9015
Fax:886-2-2782-9142
My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/wutarn_c.html
E-mail:[email protected]
Fields of Specialty:mRNA processing, Nucleocytoplasmic transport
Research Description:
Our research mainly focuses on mRNA processing and transport in eukaryotic cells.
The splicing of precursor mRNA is a key step of gene expression. In higher eukaryotes,
alternative splicing of pre-mRNAs greatly increases the complexity of the genome8. We have been
interested in the molecular mechanisms by which alternative splicing is controlled. Serine/arginine-rich
splicing factors (SR proteins) play important roles in both constitutive and regulated splicing. Dynamic
localization of splicing regulatory factors provides a means by which splicing can be regulated. We
therefore investigate the nucleocytoplasmic transport of SR proteins. We have identified an importin-
beta family member, termed transportin-SR, and found that it is responsible for nuclear import of
phosphorylated SR proteins3, 4. We have also examined the roles of SR proteins in post-splicing mRNA
maturation events9. We are interested in how cellular signaling controls phosphorylation of SR
proteins. We recently found that an SR protein becomes hyperphosphorylated upon inhibition of
mRNA synthesis and that this SR protein is destabilized when hyperphosphorylated6. In addition, we
identified a novel splicing regulatory protein, RBM4, that antagonizes the activity of SR proteins in
55
splice site and exon selection5. We also explore the molecular mechanisms of how transcription factors
control splicing regulation2 and orchestrate the assembly of the spliceosome10.
RNA export is also a key step of gene expression. We recently found that SR-like protein
Pnn/DRS becomes associated with the spliced mature mRNA during the splicing process. Our study
indicates that Pnn functions as a platform for the assembly of splicing and/or export complexes in the
nucleus7. At present, we continue to study whether phosphorylation of export factors has any effect on
mRNA export.
Selected Recent Publication:
1. Tarn, W. Y. and Steitz, J. A. Pre-mRNA splicing: the discovery of a new spliceosome
doubles the challenge. Trends Biochem. Sci. 22: 132-137, 1997.
2. Lai, M. C., Teh, B. H. and Tarn, W. Y. A human papillomavirus E2 transcriptional
activator: the interactions with cellular splicing factors and potential function in pre-
mRNA processing. J. Biol. Chem. 274: 11832-11841, 1999.
3. Lai, M. C., Lin, R. I., Huang, S. Y., Tsai, C. W. and Tarn, W. Y. A human importin-_
family protein, transportin-SR2, interacts with the phosphorylated RS domain of SR
proteins. J. Biol. Chem. 275: 7950-7957, 2000.
4. Lai, M. C., Lin, R. I. and Tarn, W. Y. Transportin-SR2 mediates nuclear import of
phosphorylated SR proteins. Proc. Natl. Acad. Sci. USA 98: 10154-10159, 2001.
5. Lai, M. C., Kuo, H. W., Chang, W. C. and Tarn, W. Y. A novel splicing regulator shares
a nuclear import pathway with SR proteins. EMBO J. 22: 1359-1369, 2003.
6. Lai, M. C., Lin, R. I. and Tarn, W. Y. Differential Effects of Hyperphosphorylation on
Splicing Factor SRp55. Biochem. J. 371: 937-945, 2003.
7. Li, C. Lin, R. I., Lai, M. C., Ouyang, P., and Tarn, W. Y. Nuclear Pnn/DRS protein binds
to spliced mRNPs and participates in mRNA processing and export via the interaction
with RNPS1. Mol. Cell. Biol. 23:7363-7376, 2003.
8. Lai, M. C. and Tarn, W. Y. Hypophosphorylated ASF/SF2 binds TAP and is present in
mRNPs.
J. Biol. Chem. (in press), 2004.
9. Li, C., and Tarn, W.-Y. Splicing. In: Encyclopedic Reference of Genomics and
Proteomics in Molecular Medicine. (ed) K. Ruckpaul and D. Ganten; Springer-Verlag.
(in press), 2004
56
10. Lin, K. T., Leu, R. M. and Tarn, W. Y. The WW domain-containing proteins interact
with the early spliceosome and facilitate 3' splice site selection. (manuscript submitted),
2004.
57
Name in Chinese:王寧
Name in English:Wang, Danny Ling
Education: University of Nevada
Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei
Title:Research Fellow, Institute of Biomedical Sciences, Academia Sinica
Tel:886-2-2652-3907, 886-2-2789-9132
Fax:886-2-2782-9143
My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/lwang_c.html
E-mail:[email protected]
Fields of Specialty:Vascular Biology, Gene Regulation ,Oxidative Stress
Research Description:
Vascular endothelial cells play an important role in maintaining vessel integrity. Oxidative stress
to endothelial cells contributes to the pathogenesis of vascular diseases. Our studies suggest that
changes of intracellular redox status may be the underlying mechanism that modulates signaling
pathways and result in alteration of gene expression in endothelial cells under chemical or mechanical
stimuli. Endothelial cells under hemodynamic flow protect themselves from cytokine-induced
responses. These protective mechanisms are not clear. Protein tyrosine phosphatases may play
important roles in suppressing signaling pathways.
In addition, endothelial cells constantly release nitric oxide that plays as a negative regulator for
endothelial responses. How nitric oxide affects signaling pathways and gene expression is not well
defined. The consequence of interplay between reactive oxygen species and nitrogen species may
determine the endothelial responses to various stimuli. Our research interests have been focusing on:
1. Signaling mechanisms and gene regulation in endothelial cells under oxidative stress.
58
2. The molecular mechanisms of shear-induced protective effects in endothelial cells
3. The role of phosphatase(s) in endothelial cells under inflammatory condition.
4. The protective role of nitric oxide in endothelial cells
5.The interaction of endothelial cells with smooth muscle cells and leukocytes that contribute to vessel
dysfunction.
Selected Recent Publication:
1. Chiu, J.J., Wung, B.S., Hsieh, H.J., Lo, L.W. and Wang, D.L. Nitric oxide regulates shear
stress-induced early growth response-1 expression via the extracellular signal-regulated
kinase pathway in endothelial cells. Circ. Res. 85: 238-246, 1999.
2. Lo, L.W., Cheng, J.J., Chiu, J.J., Wung, B.S., Lu, Y.C. and Wang, D.L. Endothelial
exposure to hypoxia induces Egr-1 expression involving PKC a-mediated Ras/Raf/ERK1/2
pathway. J. Cell. Physiol., 188: 304-312, 2001.
3. Chang, Y.L., Shen, J.J., Wung, B.S., Cheng, J.J. and Wang, D.L. Chinese herbal remedy
wogonin inhibits monocyte chemotactic protein-1 gene expression in human endothelial
cells. Mol. Pharmocol. 60: 507-513, 2001.
4. Cheng, J.J., Wung, B.S., Chao, Y.J. and Wang, D.L.Sequential activation of protein kinase
C-a and -e is required for cyclic strain-induced ERK1/2 activity in endothelial cells. J.
Biol. Chem. 276(33): 31368-31375, 2001.
5. Wung, B.S. and Wang, D. L.NO modulates monocyte chemotactic protein-1 expression in
endothelial cells under cyclic strain. Arterioscler. Thromb. Vasc. Biol. 21: 1941-47, 2001.
6. Cheng Jing-Jy, Chao Y-J and Wang D.L. “Cyclic Strain Activates Redox-Sensitive Proline-
Rich Tyrosine Kinase (PYK2) in Endothelial Cells” J. Biol. Chem. 277 (50): 48152-57,
2002.
7. Ni C-W., Wang D.L., Lien S-C., Cheng J-J., Chao Y-J, And Hsieh H-J. “Activation of
PKC- and ERK1/2 participates in shear-induced endothelial MCP-1 expression that is
repressed by nitric oxide” J. Cell. Physiol. 195:428-434 (2003).
8. Ni C-W., Hsieh H-J, Chao Y-J and Wang D.L. “Shear Flow Attenuates Serun-Induced
STAT3 Activation in Endothelial Cells.” J. Biol. Chem. 278 (22):19702-08, 2003.
9. Chen S. H., Wang D. L. “Nitric oxide inhibiting MMP–2 Expression is mediated via the
induction of activating transcription factor (ATF3) in endothelial cells.” Mol.
Pharmacology 65(5) (in press). 2004.
59
Name in Chinese:顏裕庭
Name in English:Yan, Yu-Ting
Education: University of Medicine and Dentistry of New Jersey
Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei
Title:Assistant Research Fellow, Institute of Biomedical Sciences, Academia Sinica
Tel:886-2-2652-3914 886-2-2789-9061
Fax:886-2-2785-8847
My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/yyt_c.html
E-mail:[email protected]
Fields of Specialty:Molecular Genetics, Developmental Biology
Research Description:
The left-right (L-R) asymmetry of visceral organs is known to depend on left- and right-side
specific cascades of gene expression during gastrulation and early post-gastrulation stages of
embryogenesis. Failure to establish correct pattern of L-R axis results in heterotaxy, either expressed as
randomization (situs ambiguous) or complete reversal (situs inversus) of normal organ position. In
mammals, the correct pattern of the L-R axis is very critical for viability, since defects in the L-R
laterality in newborn children are often associated with severe complex congenital cardiovascular
defects, such as atrial or ventricular septal defect (ASD or VSD) and transposition of great arteries
(TAG).
The major research interest of our laboratory is to elucidate the molecular and biochemical
mechanism of specification of L-R axis patterning of mammals, and to understand how L-R positional
information is interpreted at a tissue-specific level during organogenesis. We utilize mouse as an
experimental system, taking advantage of the assets that the system has to offer, including its small
60
size, genetics, transgenics and reverse genetics or gene targeting. Targeted disruption of mouse Cryptic
results in L-R laterality defects including randomization of abdominal situs, hyposplenia, and
pulmonary right isomerism, as well as randomized embryo turning and cardiac looping. Currently, the
work of my laboratory is focused on the following two projects: (1) investigation of L-R axis lateral
defects on the development cardiac and vascular system using Cryptic mutant mouse as a study model,
(2) identification and characterization of new candidate genes involved in determination of L-R axis.
Selected Recent Publication:
1. Iratni, R., Yan, Y.-T., Chen, C., Ding, J., Zhang, Y., Price, S. M., Reinberg, D., and
Shen, M. M. (2002). Inhibition of excess Nodal signaling during mouse gastrulation by
the transcriptional corepressor DRAP1. Science 298, 1996-1999.
2. Yan, Y.-T., Liu, J.-J., Luo, Y., E, C., Haltiwanger, R. S., Abate-Shen, C., and Shen, M.
M. (2002). Dual roles of Cripto as a ligand and co-receptor in the Nodal signaling
pathway. Mol. Cell. Biol. 22, 4439-4449.
3. Yan, Y.-T., Stein, S. M., Ding, J., Shen, M. M., and Abate-Shen, C. (2000). A novel
PF/PN motif inhibits nuclear localization and DNA binding activity of the ESX1
homeoprotein. Mol. Cell. Biol. 20, 661-671.
4. Yan, Y.-T., Gritsman, K., Ding, J., Burdine, R. D., Corrales, J. D., Price, S. M., Talbot,
W. S., Schier, A. F., and Shen, M. M. (1999). Conserved requirement for EGF-CFC
genes in vertebrate left-right axis formation. Genes Dev. 13, 2527-2537.
61
Name in Chinese:楊瑞彬
Name in English:Yang, Ruey Bing Ray
Education:University of Texas Sounthwestern Medical Center at Dallas
Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei
Title:Associate Research Fellow, Institute of Biomedical Sciences, Academia Sinica
Tel:886-2-2652-3943, 886-2-2789-9063
Fax:886-2-2785-8847
My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/rbyang_c.html
E-mail:[email protected]
Fields of Specialty:Receptor biology, Signal Transduction , Vascular Biology, Genomics
Research Description:
Current research interest of our laboratory is to unravel the biological functions of several novel
cell-surface proteins. We have previously utilized a combination of high throughput sequencing and
genome-wide microarray profiling analyses to identify novel cell-surface proteins expressed in human
umbilical vein endothelial cells. One gene family identified by this approach encodes potential
secreted proteins harboring multiple copies of epidermal growth factor-like domain and one CUB
domain at the carboxyl terminus. Recently, we have identified one additional member with an
osteoblast-enriched expression profile that is completely distinct from the endothelial expression of
two previously identified family members. Recent immunohistochemical staining and molecular
genetic studies suggested that members of this gene family may play important roles in the
pathogenesis of cardiovascular or bone diseases.
Another gene identified by this approach encodes a novel type I transmembrane receptor
expressed in a testis-specific fashion. In the near future, we will apply molecular and biochemical
62
methodologies as well as gene targeting approach to further evaluate their functions in the
cardiovascular, bone and reproductive biology.
Selected Recent Publication:
1. Brightbill, H.D., Libraty, D.H., Krutzik, S.R., Yang, R.-B., Belisle, J.T., Maitlan, M.,
Norgard, M.V., Plevy, S.E., Smale, S.T., Brennan, P.J., Bloom, B.R., Godowski, P.J.,
and Modlin, R.L. Microbial lipoproteins trigger host defense mechanisms via Toll-like
receptors. Science 285: 732-736, 1999.
2. Yang, R.-B., Mark, M.R., Gurney, A.L., and Godowski, P.J. Signaling events induced by
lipopolysaccharide-activated Toll-like receptor-2. J. Immunol. 163: 639-643, 1999.
3. Yang, R.-B., Robinson, S.W., Birch, D.G., and Garbers, D.L. Disruption of a retinal
guanylyl cyclase gene leads to cone-specific dystrophy and paradoxical rod behavior. J.
Neurosci. 19: 5889-5897, 1999.
4. Aliprants, A.O., Yang, R.-B., Weiss, D.S., Godowski, P.J., and Zychlinsky, A. The
apoptotic signaling pathway activated by Toll-like receptor 2. EMBO J. 19: 3325-3336,
2000.
5. Hollopeter, G., Jantzen, H.-M., Vincent, D., Li, G., England, L., Ramakrishnan, V.,
Yang, R.-B., Nurden, P., Nurden, A., Julius, D., and Conley, P.B. Molecular
identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature 409:
202-207, 2001.
6. Yang, R.-B., Ng, C.K.D., Wasserman, S.M., Komuves, L.G., Tomlinson, J.E., and
Topper, J.N. Identification of a family of cell-surface proteins expressed in human
vascular endothelium. J. Biol. Chem. 277: 46364-46373, 2002.
7. Wasserman, S.M., Mehraban, F., Komuves, L.G., Yang, R.-B., Tomlinson, J.E., Spriggs,
F. and Topper, J.N. Gene Expression profile of human endothelial cells exposed to
sustained fluid shear stress. Physiol. Genomics 12: 13-23, 2002.
8. Yang, R.-B.*, Ng, C.K.D., Wasserman, S.M., Komuves, L.G., Gerritsen, M.E., and
Topper, J.N. A novel IL-17 receptor-like protein identified in human umbilical vein
endothelial cells antagonizes basic fibroblast growth factor-induced signaling. J. Biol.
Chem. 278: 33232-33238, 2003. (* Corresponding author)
9. Kuhn, M., Ng, C.K.D., Su, Y.-H., Kilic, A., Mitko, D., Bien-Ly, N., Komuves, L.G.,
Yang, R.-B. Identification of a novel receptor guanylyl cyclase selectively expressed in
63
mouse testis. Biochem. J. 379: 385-393, 2004.
64
Name in Chinese:嚴仲陽
Name in English:Yen, Jeffrey J.Y.
Education: Baylor College of Medicine
Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei
Title:Research Fellow, Institute of Biomedical Sciences, Academia Sinica
Tel:886-2-2652-3077 886-2-2789-9017
Fax:886-2-2782-9142
My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/yen_c.html
E-mail:[email protected]
Fields of Specialty: Molecular & Cell Biology, Hematopoiesis, Apoptosis Regulation
Research Description:
The long term interest of my laboratory has been on the growth and death regulation of
hematopoietic cell lineages due to the underlying mechanism may shed lights on many human
detrimental diseases, including leukemia, immunodeficiencies, allergic disorders, asthma, and
autoimmunities. In the past ten years, we have applied standard molecular and cellular biology
techniques to pursue our goals in terms of involvement of specific genes in the death regulation of
hematopoietic cells. We continued to work on the molecular mechanism triggering the programmed
cell death when cytokine was depleted. A novel cytokine receptor associated signaling molecule as
well as a novel cytokine deprivation-induced early gene are identified. They both were found to be
strongly apoptogenic to hematopoietic cells, suggesting the likelihood of the involvement of these
novel molecules in this process. On the other hand, we discovered the involvement of the erythroid
transcriptional factor GATA-1 in transducing anti-apoptotic acitivity of interleukin 3 in cytokine
dependent hematopoietic cell line. Intriguingly, there is a strong correlation between tissue expression
65
profile of GATA family members and their target anti-apoptotic gene E4BP4, suggesting the survival
effect of GATA family proteins may play an important role in multiple organ development.
In the new millennium, we also included molecular genetic and functional genomic approaches to
tackle the regulatory mechanism of apoptosis control. We are currently actively participating in the
genome-wide phenotype-driven ENU-mutagenized mice screening program for the hematopoietic
deficiency phenotype. Once the mutation is confirmed and chromosomal location is mapped, high-
resolution genetic mapping and molecular cloning of the defected gene will be pursued using various
genomic research tools, such as SNP discovery, bioinformatics and transgenic rescue. We are at present
working on a mutant mouse line with segmental progeroid symdrome and another line with
lymphocytopenia and combined immune deficiency. Our preliminary study suggested that both
mutations affect the survival of either stem cell population or lymphoid cell lineages.
Selected Recent Publication:
1. Huang, H.M., Li, J.C., Hsieh, Y.C., Yang-Yen, H.F. and Yen, J.J.Y. Optimal proliferation
of a hematopoietic progenitor cell line requires either costimulation with stem cell
factor or increase of receptor expression that can be replaced by overexpression of Bcl-
2. Blood 93: 2569-2577, 1999.
2. Lee, S.F., Huang, H.M., Chao, J.R., Lin, S., Yang-Yen, H.F. and Yen, J.J.Y. Cytokine
receptor common a chain as a potential activator of cytokine withdrawal-induced
apoptosis. Mol. Cell. Biol. 19: 7399-7409, 1999.
3. Huang, H.M., Huang, C.J. and Yen, J.J.Y. Mcl-1 is a common target of stem cell factor
and interleukin 5 for apoptosis prevention activity via MEK/MAPK and PI-3K/Akt
pathways. Blood 96: 1764-1771, 2000.
4. Chen, W., Yu, Y.L., Lee, S.F., Chiang, Y.J., Chao, J.R., Huang, J.H., Chiong, J.H.,
Huang, C.J., Lai, M.Z., Yang-Yen, H.F. and Yen, J.J.Y. CREB is one component of the
binding complex of the Ces-2/E2A-HLF binding element and is an integral part of the
IL-3 survival signal. Mol. Cell. Biol. 21: 4636-4646, 2001.
5. Yu, Y.L., Chiang, Y.J., and Yen, J.J.Y. GATA factors are essential for transcription of the
survival gene E4BP4 and the viability response of interleukin-3 in Ba/F3 hematopoietic
cells. J. Biol. Chem.277:27144-27153, 2002.
66
Name in Chinese:蕭百忍
Name in English:Yen, Pauline, H.
Education: University of California, Berkeley
Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei
Title:Research Fellow, Institute of Biomedical Sciences, Academia Sinica
Tel:886-2-2652-3912 886-2-2789-9055
Fax:886-2-2782-9224
My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/pyen_c.html
E-mail:[email protected]
Fields of Specialty:Human Genetics
Research Description:
The mammalian sex chromosomes play important roles in spermatogenesis. More than half of the
genes on the human Y chromosome and numerous genes on the X chromosome are expressed
exclusively in the testis. Microdeletion of the Y chromosome and the presence of an extra X
chromosome in the Klinefelter syndrome patients are two major causes of male infertility. Our
research focuses on the Deleted in Azoospermia (DAZ) gene family on the Y chromosome long arm
that is frequently deleted in infertile men. We perform functional analyses of the DAZ protein and
study polymorphisms associated with the DAZ genes in the male population. Our results indicate that
sister chromatid exchange plays a significant role in Y chromosome polymorphism. We also study two
X-linked genes with testis-specific expression to test the hypothesis that the spermatogenic failure in
Klinefelter syndrome patients is caused by increased expression of X-linked spermatogenesis genes
during male germ cell development. We study the temporal and spatial expression of Tex11 and Usp26
during testis development, determine their subcellular localization, and generate null mutants to
67
elucidate their functions.
Selected Recent Publication:
1. Yen, P.H. Advances in Y-chromosome mapping. Curr. Opin. Obstet. Gynecol. 11:275-
281, 1999.
2. Tsui, S., Dai, T., Warren, S.T., Salido, E.C., and Yen, P.H. Association of the infertility
factor DAZL1 with actively translating polyribosomes. Biol. Reprod. 62:1655-1660,
2000.
3. Tsui, S., Dai, T., Roettger, S., Schempp, W., Salido, E.C., and Yen, P.H. Identification of
two novel proteins that interact with germ-cell specific RNA-binding proteins DAZ and
DAZL1. Genomics, 65:266-273, 2000.
4. Moro, E., Ferlin, A, Yen, P.H., Franchi, P.G., Palka, G., and Foresta C. Male infertility
caused by a de novo partial deletion of the DAZ cluster on the Y chromosome. J. Clin.
Endocrinol. Metab. 85:4069-4073, 2000
5. Roettger, S., Pasantes, J.J., Baldermann, C., Reichl, E., Yen, P.H., Hansmann, I.,
Schempp, W. Familial mosaicism of del(Y) and inv del(Y). Cytogenet. Cell Genet.
91:208-211, 2000.
6. Lue, Y., Rao, P.N., Sinha Hikim, A.P., Im, M., Salameh, W, Yen, P.H., Wang, C., and
Swerdloff, R.S. Progressive loss of germ cells by apoptosis in XXY male mice: An
experimental model for Klinefelter Syndrome. Endocrinology 142:1461-1470, 2001.
7. Yen, P. The fragility of fertility. NatureGenet. 29:243-244, 2001.
8. Vera, Y., Dai, T., Lue, Y., Sinha-Hikim, A.P., Salido, E.C., Swerdloff, R.S., and Yen,
P.H. DAZAP1, a DAZ associated protein, shuttles between nucleus and cytoplasm
during normal germ cell maturation. J. Andrology 23:622-628, 2002.
9. Roettger, S., Yen, P.H., and Schempp, W. A fiber-FISH contig spanning the non-
recombining region of the human Y chromosome. Chrom. Res. 10:621-635, 2002.
10.Yen PH (2004) Putative biological functions of the DAZ family. Int. J. Androl. 27: 125-
129.
68
Taiwan International Graduate Program
Molecular Medicine Program
National Yang Ming University Faculty
69
Name in Chinese:張國威Name in English:Kuo-Wei Chang
Education:1983, DDS, National Yang-Ming University
1995, PhD, Department of Pathology, Northwestern University
Affiliation:Department of Dentistry, National Yang-Ming University
Title:Professor
Tel:886-2-2826-7223
Fax:886-2-2826-4053
My Personal Homepage:http://www.ym.edu.tw/iob
E-mail:[email protected]
Fields of Specialty:Oral Pathology/Molecular Pathology
Research Description:My investigation targets on oral carcinogenesis. Identification of tumor markers and karyotypic
dissection of oral cancers have been my major research topics.
Selected Recent Publication:1. Liu SY, Yang SC, Yen CY, Chang KW* (2004, In press) Overexpression of Rac-1 small GTPase
binding protein in areca quid-associated oral squamous cell carcinoma. J Oral Maxillofac Surg.
2. Wong YK, Lin SC, Liu CJ, Tzeng YS, Lin HC, Wong CY, Chang KW* (2003) Cyclin D1
genotype in areca-associated oral squamous cell carcinoma. J Oral Pathol Med 32: 265-70.
3. Chang, KW , Kao, SY, Tzeng RJ, Liu, CJ, Cheng AJ, Wong, YK, Yang SC and Lin SC* (2002)
Multiple molecular alterations of FHIT in betel-associated oral squamous cell carcinoma. J
Pathol 2002 196:300-6.
4. Lin SC, Chen YJ, Hsu MD, Chang CS, Liu TY, Lin CH and Chang KW* (2002) The
chromosomal changes of oral squamous cell carcinoma associated with betel quid use. Oral
Oncol 38: 266-73.
5. Chang KW , Lin SC, Chao SY, Kwan PC and Wong YK* (2001) Establishment and
characterization of a new oral melanoma cell line (ME). Oral Oncol 37: 301-7.
6. Chang KW, Lin SC, Kwan PS and Wong YK* (2000) Association of p53/p21waf1 expression with
70
outcomes of veruccous leukoplakia in Taiwan. J Oral Pathol Med 29: 56-62.
7. Chang, KW, Sarraj S, Lin SC, Tsai, PI and Solt DB* (2000) p53 expression, p53 and Ha-ras
mutation, and telomerase activation during nitrosamine-mediated hamster pouch carcinogenesis.
Carcinogenesis 21: 1441-51.
8. Chang KW* , Lin SC, Wong YK, Liu TY and Chang CS (2000) Alterations of APC in oral
squamous cell carcinoma in Taiwan. Int J Oral-Maxillofac Surg 29: 223-6.
9. Chang LY, Lin SC, Chang CS, Wong YK, Hu YC and Chang KW* (1999) Telomerase activity
and in situ telomerase RNA expression in oral carcinogenesis. J Oral Pathol Med 28: 389-396.
10. Chen YJ, Lin SC, Kao T, Chang CS, Hong PS, Shieh TM and Chang KW* (In Revision) Genome
profiling of oral squamous cell carcinoma and identification of Serpine1 (Plasminogen Activator
Inhibitor-1, PAI-1) expression as an important event for oral carcinogenesis. J Pathol.
71
Name in Chinese:張泰階Name in English:Tai-Jay Chang
Education:PhD, Molecular Cellular Pathology, Mt. Sinai Medical School, USA
Affiliation:Veterans General Hospital-Taipei, Genome research Laboratory
Institute of Biomedical Technology, National Yang-Ming University
Title:Associated Principal Investigator
Tel:886-2-2871-2121 ext 2681
Fax:886-2-2876-3260
My Personal Homepage:http://www.mre.vghtpe.gov.tw/laboratory/genome_research/index.htm
E-mail:[email protected]
Fields of Specialty:Molecular Biology, Human Genome Research,Steroid Hormone Receptors
Transcription Regulation
Research Description:Functional Genomic approaches in cancer genome research
Selected Recent Publication:
1. Chen, Y.M., Chen, W.C., Lee, J.Y., Chang, T.J. and Yang-Feng, T. Genomic structeure,
expression and chromosomal localization of the human glycine N-methyltransferase. Genomics,
66:43-47, 2000.
2. Chen, Y.M., Chen, W.C., Lee, J.Y., Chang, T.J. and Yang-Feng, T. Genomic structeure,
expression and chromosomal localization of the human glycine N-methyltransferase. Genomics,
66:43-47, 2000.
3. Chan, J.Y.H., Chen, W.C., Lee, J.Y., Chang, T.J.and Chan, S.H.H.Phosphorylation of
transcription factor CREB mediates c-fos Induction elicited by sustained hypertension in rat
nucleus tractus Solitarii. Neuroscience 88:1199-1212,1999
4. Tu,T.Y., Chiu, J.H., Chang, T.J., Yang, A.H. and Lien C.F. Expression of Isk protein mRNA in
cultured rat strial marginal Cells. Acta Otolaryngol 119:544-549,1999
5. Chang TJ, Tsai TC, Yang HM, Wu YL, Chi CW, Chou MD and Lee LS. 1999 Abnormal
transcripts of FHIT gene in Chinese brain tumors. Oncology Report 6:345-348,1999
72
6. Chan, J.Y.H., Chen, W.C., Lee, J.Y., Chang, T.J.and Chan, S.H.H.Phosphorylation of
transcription factor CREB mediates c-fos Induction elicited by sustained hypertension in rat
nucleus tractus Solitarii. Neuroscience 88:1199-1212,1999
7. Tu,T.Y., Chiu, J.H., Chang, T.J., Yang, A.H. and Lien C.F. Expression of Isk protein mRNA in
cultured rat strial marginal Cells. Acta Otolaryngol 119:544-549,1999
73
Name in Chinese:陳正成 Name in English:Cheng-Chen Chen
Education:London School of Hygiene and Tropical Medicine. Ph. D. 1982
National Defense Medical Center, M. Sc. 1975
National Chung-Hsing University, B. Sc. 1973
Affiliation:Institute of Tropical Medicine, National Yang-Ming University
Title:Professor
Tel:886-2-2826-7074
Fax:886-2-2821-4670
E-mail:[email protected]
Fields of Specialty:Medical Entomology, Vector Biology, Mosquito innate immunity, Mosquito
genome.
Research Description: My work involves using genomic mass-screens, EST sequencing, microarray analysis, and
proteomics, etc., to identify important mosquito defense factors. The potential candidate molecules are
characterized and elucidated their biological functions by mosquito gene silencing technologies.
Selected Recent Publication:1. Huang, L.H., Christensen, B.M. and Chen, C.C. 2001, Molecular cloning of a second
prophenoloxidase cDNA from the mosquito Armigeres subalbarus: prophenoloxidase expression
in blood-fed and microfilariae-inoculated mosquitoes. Insect Molecular Biology 10: 87-95
2. Taft, A. S., Chen, C. C., Li, J. and Christensen, B.M 2001 Molecular cloning of two
prophenoloxidase genes from mosquito Aedes aegypti. Insect Molecular Biology 10: 97-103
3. Shiao, H. S., Higgs, S., Adelman, Z., Christensen, B. M., Liu, S. H. and Chen, C. C. 2001 Effect
of prophenoloxidase expression knockout on the melanization of filarial worms in the mosquito,
Armigeres subalbatus. Insect Molecular Biology 10: 315-321
4. Lai, S. C., Chen, C. C. and Hou, R. F. 2001. Electron microscopic observation on wound healing
in larvae of the mosquito Armigeres subalbatus (Diptera:Culicidae). Journal of Medical
Entomology 38: 836-843
5. Chang, T.T., Chang T.Y., Chen, C.C., Young, K.C., Roan, J. N., Lee., Y.C., Cheng, P.N. and Wu,
74
H.L. 2001 Existence of hepatitis C virus in Culex quinquefasciatus after ingestion of infected
blood: experimental approach to evaluating transmission by mosquitoes. Journal of Clinical
Microbiology 39: 3353-3355
6. Lai, S.C., Chen, C.C. and Hou, R.F. 2002. Immunolocalization of prophenoloxidase in the process
of wound healing in larvae of the mosquito Armigeres subalbatus (Diptera: Culicidae). Journal of
Medical Entomology 39:266-274
7.Johnson, J.K., Rocheleau, T. A., Hillier, J.F., Chen, C.C., Li, J., Christensen,B.M. 2003. A potential
role for phenylalanine hydroxylase in mosquito immune responses. Insect Biochemistry and
Molecular Biology 33:345-354
8. Bartholomay, L. C., Cho, W. L., Rocheleau, T. A. Boyle, J. P., Beck, E. T., Fuchs, J. F., Liss, P.,
Rusch, M., Butler, K. M., Wu, R. C. C., Lin, S. P., Kou, H. Y., Tsao, I. Y., Huang, C. Y., Wu, T. T, .
Hsiao, K. J., Tsai, S. F., Yang, U. C., Nappi, A. J., Perna, N. T., Chen, C. C., and Christensen, B.
M. 2004. Toward a description and transcriptomes of immune-activated hemocytes from the
mosquito vectors, Aedes aegypti and Armigeres subalbatus. Infection and Immunity (in press).
9. Wang, X., Roucheleau, T. A., Fuchs, J. F., Hillyer, J. F., Chen, C. C. and Christensen, B. M. 2004.
A novel lectin with a fibrinogen-like domain is involved in innate immune response of Armigeres
subalbatus against bacteria. Insect Molecular Biology (in press).
75
Name in Chinese:陳紀如Name in English:Chi-Ju Chen
Education: Ph.D.Genetics Program , Michigan State University, USA
Affiliation:National Yang-Ming University, Taiwan
Title:Assistant Professor
Tel/Fax:886-2-2826-7180
E-mail:[email protected]
Field of specialty:Virology, virus-host interaction
Research Interests:Epstein-Barr virus (EBV) is a human gamma herpesvirus associated with a number of
malignancies, including nasopharyngeal carcinoma (NPC), Burkitt’s lymphoma, T-cell lymphoma,
gastric carcinoma, and Hodgkin’s disease. EBV is transmitted orally, infects both mucosal epithelium
and B-lymphocytes where it establishes a latent infection in B-lymphocytes. The EBV genome is
maintained as a chromatin-like episome at latency. High levels of reactivation are thought to be a risk
factor for several EBV-related malignant lymphoid cancers. However the role of EBV in human
malignancy is complex and how the virus is reactivated is not well understood. The expression of
immediate early gene, Zta, is a key step in the switch from latency to the lytic cycle of EBV. Zta binds
to specific sequences, ZREs, found in viral lytic-cycle origin (OriLyt), as well as viral promoters of
genes required for lytic DNA replication. Zta binding to its own promoter is thought to be a key step in
the autostimulation of Zta transcription. It was shown that Zta binds to a cellular factor, CREB-binding
protein (CBP), which processes acetyltransferase activity, and reactivation of latent EBV by Zta can be
strongly stimulated by co-expression of CBP. Zta stimulates CBP acetyltransferase activity on
nucleosomes.
A switch to expression of viral replication-associated genes can be achieved by treatment with
histone deacetylase inhibitors, Tricostatin A (TSA) and sodium butyrate, suggesting the involvements
of acetyltransferase activity in EBV reactivation. Zta interacts with CBP and stimulates its
acetyltransferase activity. Our goal is to investigate the biological role of Zta-depend CBP
acetyltransferase activity on Epstein-Barr virus (EBV) reactivation. Three specific aims are the recent
interests:1. Determine the effect of CBP on BZLF1 promoter and other Zta responsive viral genes upon
reactivation.
76
2. Identify the HAT activity of CBP on oriLyt and how it affects EBV replication.
3. Determine the significance of acetylation modification of Zta by CBP.
Publications:1. Deng. Z., C-J Chen, M. Chamberlin, F. Lu,1 G. A. Blobel, D. Speicher,
L. A. Cirillo, K. S. Zaret, and P. M. Lieberman1. 2003. The CBP bromodomain and nucleosome
targeting are required for Zta-directed nucleosome acetylation and transcription activation.
Molecular and Cellular Biology 23:2633-2644.
2. Deng. Z., L. Lezina, C-J Chen, S. Shtivelband, W. So, and P. M. Lieberman. 2002. Telomeric
proteins regulate episomal maintenance of Epstein-Barr virus origin of plasmid replication.
Molecular Cell 9: 493-503.
3. Deng, Z.*, C-J Chen*, D. Zerby, H. Delecluse, P. M. Lieberman. 2001. Identification of acidic and
aromatic residues in the Zta activation domain essential for Epstein-Barr virus reactivation.
Journal of Virology 75: 10334-10347. (co-first authors).
4. Chen, Chi-Ju, Z. Deng,, A. Kim, G. Blobel, and P. M. Lieberman. 2000. Stimulation of
nucleosome-directed histone acetylase activity of CBP by transcriptional activators. Molecular
and Cellular Biology 21:476-487.
5. Zerby, D, C-J Chen, E. Poon, D. Lee, R. Shiekhattar, and P. M. Lieberman. 1999. The amino-
terminal C/H1 domain of CREB binding protein mediates Zta transcriptional activation of latent
Epstein-Barr virus. Molecular and Cellular Biology 19: 1617-1626.
6. Chen, Chi-Ju, M. E. Quentin, L. A. Brennan, C. Kukel, and S. M. Thiem. 1998. Lymantria dispar
Nucleopolyhedrovirus hrf-1 expands the larval host range of Autographa californica
nucleopolyhedrovirus. Journal of Virology 72: 2526-2531.
77
Name in Chinese:陳志成Name in English:Jyh-Cheng Chen
Education:1992-1995 PhD, Optical Sciences, University of Arizona, Tucson, Arizona, USA
Affiliation:1998-date Institute of radiological Sciences and Department of Medical Radiation
Technology.
Title:Associate Professor
Tel:886-2-2826-7282
Fax:886-2-2820-1095
My Personal Homepage:http://140.129.65.185/
E-mail: [email protected]
Fields of Specialty:
Nuclear molecular imaging physics and instrumentation, medical image processing and analysis
Research Description: Dr. Chen is using clinical PET and microPET to do image reconstruction,
processing and analysis for clinical and animal studies. Currently he is promoting the NYMU Small-
animal Gamma-ray Imaging Laboratory under the collaboration from UST.
Selected Recent Publication:
1. C.H.Wang, JC Chen*, and RS Liu, (2003): Development and evaluation of MRI based Bayesian
image reconstruction methods for PET. Comput. Med. Imag. Grap. (2003) (in press). (SCI)
2. Wang HE, Liao AH, Deng WP, Chang PF, Ch en JC , Chen FD, Liu RS, Lee JS, Hwang JJ.
Evaluation of 4-Borono-2-[18F]Fluoro-L-Phenylalanine-Fructose as a Probe for BNCT in a
Glioma-Bearing Rat Model. J Nucl. Med. 2004; 45:302-308. (SCI)
3. S.P.Mok, C.H.Wang, JC Chen*, and RS Liu, (2003): Performance evaluation of a high resolution
small animal PET scanner. Biomed. Eng. Appl. Basis Comm. 15: 143-149. (EI) (NSC 91-3112-P-
075-003-Y)
4. Tracy Chen, KS Chuang*, JC Chen, Jay Wu, ML Jan, RS Liu, and CH Hsu, (2003):
Simplification of the Probability Matrix in Statistical Reconstruction for PET image. Ann. of
Nucl. Med. Sci. 2003:16;137-142.
5. C.H.Wang, JC Chen*, CM Kao, and RS Liu, (2003): Evaluation of MR Images Guided Bayesian
78
Image Reconstructions for PET. Proc. IEEE Nuclear Science Symposium and Medical Imaging
Conference (in press). (EI)
6. X.X.Ye, J.J.Hwang, J.F.Hsieh, J.C.Chen*, Y.T.Chou, K.Y.Tu, S.P.Wey, and G.Ting, (2003): In
Vivo Quantification of bound [123I]ADAM in Serotonin Transporters in the Brains of Rabbits by
SPECT (submitted to Nuclear Medicine and Biology and in revision).
7. Ye XX, Chen JC, Hwang JJ, Wey SP, Lin KJ, Lee JS, Tzen KY, Ting G., (2003):
Microautoradiography of [123I]ADAM in mice treated with fluoxetine and serotonin reuptake
inhibitor. Nuclear Medicine and Biology (in press). (SCI)
79
Name in Chinese:陳美瑜Name in English:Mei-Yu Chen
Education:M.D., National Yang-Ming Medical College
Ph.D., BCMB program, Johns Hopkins University School of Medicine
Affiliation:Department of Biochemistry, School of Medicine, Nationatl Yang-Ming University
Title:Associate professor
Tel:886-2-2826-7269
Fax:886-2-2826-4843
My Personal Homepage:http://biochem.ym.edu.tw/mychen/
E-mail:[email protected]
Fields of Specialty:Biochemistry, Molecular Biology
Research Description:Mechanism and regulation of amoeboid chemotaxis
Amoeboid chemotaxis is of fundamental importance in cell-mediated immunity as well as tumor
invasion and metastasis. Dictyostelium provides an excellent model system for studying chemotaxis
since this organism spends most of its life cycle as chemotactic amoeboid cells and chemotaxis plays a
pivotal role during its starvation-induced developmental program. We perform mutagenesis in
Dictyostelium, screen for mutants with aberrant chemotactic behaviors, and from the collected mutants,
identify and clone the genes responsible for the phenotype. Further analyses of the identified novel
genes and their homologs in mammals should provide more insights into the molecular mechanism and
regulation of eukaryotic chemotaxis.
Cellular functions of Pianissimo homologs
Pianissimo (piaA) was first identified in Dictyostelium as a novel cytosolic protein involved in
cAMP signaling pathway. Genes homologous to piaA exist in Saccharomyces cerevisiae and
Schizosaccharomyces pombe. Using a combination of molecular and genetic methods, we have found
that the S. cerevisiae homolog (PIA1) is involved in modulating cell integrity and interacts functionally
with the target of rapamycin (Tor2p) signaling pathway. In yeast, Tor2p controls cell growth and
regulates the cell cycle-dependent organization of actin cytoskeleton. Further studies are underway to
80
elucidate the role of PIA1 in these signaling pathways.
Selected Recent Publication:
1. Pang, T.L., Wang, C.Y., Hsu, C.L., Chen, M.Y., and Lin, J.J. (2003) Exposure of single-
stranded telomeric DNA causes G2/M cell cycle arrest in Saccharomyces cerevisiae. J. Biol.
Chem. 278, 9318-9321.
81
Name in Chinese:陳宜民Name in English:Yi-Ming Arthur Chen M.D., M.S., Sc.D.
Education:D.Sc. degree at the Department of Cancer biology of Harvard School of Public Health
Affiliation:Director, AIDS Prevention and Res. Center, National Yang-Ming Uni.
Member, AIDS Advisory Committee, D.O.H., R.O.C
President, Taiwan Society of Preventive Medicine
Council of Representative, APCASO
Title:Professor and Chair, Institute of Public Health National Yang-Ming University
Tel:886-2-2826-7193
Fax:886-2-2827-0576
E-mail:[email protected]
Fields of Specialty:The Institute of Public Health of NYMU in Taiwan. Prof. Chen has authored/co-authored more than
50 publications on HIV-1, HTLV-I and liver cancer genomics. He also translated Dr. Jonathan Mann’s
“AIDS in the World, 2nd edition” into Chinese. At present, he is the president of the Preventive
Medicine Society of Taiwan and board member of several advisory committees which including the
APCASO (Asia Pacific AIDS Services Organization), amfAR (American Foundation for AIDS
Research)- TREAT Asia program, Praa (PWA’s Rights Advocacy Association of Taiwan), the
Department of Health and the Ministry of Education of ROC.
Research Description:Cancer
Selected Recent Publication: 1. Chen Y-J, Shih L-S and Chen YM. Quantitative analysis of CDKN2, p53 and
retinoblastoma mRNA in human gastric carcinoma. Int J Oncol 13: 249-254, 1998.
2. Chen YM*, Ting S-T, Lee C-M, W-T Liu, Pan W-H, TA Chang, Chou P. Community-
based molecular epidemiology of human T-cell leukemia virus type I infection in Taiwan
and Kinmen: Implication of the origin of the cosmopolitan subtype in North East Asia.
AIDS Res Human Retroviruses 15: 229-237, 1999.
82
3. Liao Y-P and Chen YM. The legal prostitute's space in Taipei city: stories of secret path,
wood-sandals and seven dollars. The Con-temporary Magazine, 137: 44-65, 1999.
4. Chen YM*, Chen LY, Wong FH, Lee CM, Chang TJ, Yang-Feng TL. Genomic structure,
expression and chromosomal localization of the human glycine N-methyltransferase gene.
Genomics 66: 43-47, 2000.
5. Liou YM, Chou P, Chen YM*. Genotypic Analysis of HCV infection in Kinmen. J
Microbiol Immunol Infect 33: 63-68, 2000.
6. Chen YM*, Huang KL, Jen I, Chen SC, Liu YC, Chuang YC, Wong JC, Tsai JJ. Temporal
trends and molecular epidemiology of HIV-1 Subtypes in Taiwan from 1988 to 1998. J
Acquir Immun Defic Syndr Hum Retrovirol 26: 274-282, 2001.
7. Yang MH, Wang KY, Kuo B IT, Chen YM. Quality of life and its related factors for
people living with HIV/AIDS in the northern region of Taiwan. J Nursing Res submitted
2002.
8. Chen YM*, Rey WY, Lan YC, Lai SF, Huang YC, Wu SI, Liu TT, Hsiao KJ. Antibody
reactivity to HIV-1 Vpu in HIV-1/AIDS patients on highly active antiretroviral therapy. J
Biomed Sci 10: 266-275, 2003.
9. Liu HH, Chen KH, Shih YP, Lui WY, Wong FH, Chen YM*. Characterization of reduced
expression of glycine N-methyltransferase in the cancerous hepatic tissues using two
newly developed monoclonal antibodies. J Biomed Sci 10: 87-97, 2003.
10. Tseng TL, Shih YP, Huang YC, Wang CK, Chen PH, Chang JG, Yeh KT, Chen YM*,
Buetow K. Genotypic and phenotypic characterization of a putative tumor susceptibility
gene, GNMT, in liver cancer. Cancer Res, 63: 647-654, 2003.
83
Name in Chinese:鄭宏志Name in English:Henrich Cheng
Education:Karolinska Institute / Dept. of Neuroscience / Ph.D. / 1993 / 03 to1996 / 12
Affiliation : Taipei Veterans General Hospital, Center for Neural Regeneration, Department of
Neurosurgery, Neurological Institute
Title:Chief and Associate Professor
Tel:886-2-2875-7718
Fax:886-2-2875-7702
E-mail:[email protected]
Fields of Specialty:Neurosurgery, Neurochemistry, Cell biology
Research Description:Dr. Cheng has devoted his life to research in the field of neural regeneration for more than one
decade. Recent breakthroughs in molecular neurobiology have ushered in a new and exciting era of
central nervous system repair, lending hope to the possibility of functional recovery. Through the use
of peripheral nerve grafts supported by growth factor containing fibrin glue, animal studies have
demonstrated partial restoration of hind limb function in adult paraplegic rats. (Science, 1996) Using
similar methods, substantial recovery of forelimb function was achieved in adult rats with avulsed
cervical roots. (Experimental Neurology, 2003) Since 2000, neural repair clinical trials of the spinal
cord, brachial plexus, and peripheral nerves have been performed. The results of these experiments are
encouraging.
At present, Dr. Cheng supervises the Neural Regeneration Laboratory at Taipei Veterans General
Hospital, Taipei, Taiwan. There are over twenty researchers in the lab conducting proteomic studies
and gene research, integral facets of neural regeneration. In addition, advanced cell therapy research in
stem cells and olfactory ensheathing cells is also being conducted, along with microglia and related
molecule studies including metalaproteinase and metalaprotein. Another team at Dr. Cheng’s
laboratory is working on multi-channel brain and spinal cord recording in order to monitor central
nervous system electrophysiology before and after operative repair. Animal model trials including
stroke, spinal cord injury, spinal cord contusion and spinal root injury are also being investigated. A
further development includes the novel rehabilitation program, which includes magnetic stimulation
and virtual reality based computer feedback models. Neural prosthetic work utilizing bio-material and
84
nano-technology are also underway. These research developments look to the future and aim for
functional recovery and regeneration in central nervous system injuries and diseases.
Selected Recent Publication:1. Cao Y, Veitonmaki N, Keough K, Cheng H, Lee LS, Cao Y, and Zurakowski D. Elivated Levels of
Urine Angiostatin and Plasminogen/ Plasmin in Cancer Patients. International Journal of Molecular
Medicine 2000; 5: 547-551.
2. Tzeng SF, Tai MH, Cheng H, Wu JP, Liu YL, Kuo JS, Lin PR. Use of Adenoviral Gene Transfer
of Glial Cell Line Derived Neurotrophic Factor for Spinal Cord Repair Following a Contusive
Injury. J Neurochem 2000; 74: S77B.
3. Chuang TY, Huang MC, Chen KC, Chang YC, Yen YS, Lee LS, and Cheng H. Forelimb Muscle
Activity Following Nerve Graft Repair of Ventral Roots in the Rat Cervical Spinal Cord. Life
Sciences. 2002; 71, 487-496.
4. Cheng H and Lee YS. Spinal Cord Repair Strategies in Spinal Cord Medicine: Principles and
Practice. Demos Medical Publishing, New York; 2002; Chapter 59, P. 801-816.
5. Cheng H, Wu JP, and Tzeng SF. Neuroprotection of Glial Cell Line-Derived Neurotrophic Factor
in Damaged Spinal Cords Following Contusive Injury. Journal of Neuroscience Research 2002; 69:
397-405.
6. Cheng H, Fu YS, Kuo JW. The Ability of GDNF to Diminish Free Radical Production Leads to
Protection Against Kainate-Induced Excitotoxicity in Hippocampus. Hippocampus 2003
(accepted).
85
Name in Chinese:鄭子豪Name in English:Tzu-Hao Cheng
Education:PhD, Rutgers University/UMDNJ
Postdoctoral fellow, Stanford University School of Medicine
Affiliation:Biochemistry Institute of Yang-Ming University
Title:Assistant Professor
Tel:886-2-2826-7331
Fax:886-2-2826-4843
My Personal Homepage: under development
E-mail:[email protected]
Field of Specialty:Molecular Biology, Molecular Genetics
Research Description:1. The functions of human MDM2 isoforms which are generated by alternative translation initiation
2. Polyglutamine mediated protein aggregation
Selected Recent Publication:
1. Cheng, T.H. , Li, Y.C., and Gartenberg, M.R. (1998). Persistence of an alternate
chromatin structure at silenced loci in the absence of silencers. Proc. Natl. Acad. Sci.
USA 95, 5521-5526.
2. Ansari A., Cheng, T.H., and Gartenberg, M.R. (1999). Isolation of chromatin rings from
yeast employing site-specific recombination in vivo. Method: A Companion to Methods
in Enzymology 17, 104-111.
3. Cheng, T.H. and Gartenberg M.R. (2000). Yeast silent chromatin is a dynamic structure
that requires silencers continuously. Genes & Dev. 14, 452-463.
4. Cheng, T.H. , Chang, C.R., Joy, P., Yablok, S., and Gartenberg, M.R. (2000). Controlling
gene expression in yeast by inducible site-specific recombination. Nucleic Acids Res. 28,
e108.
5. Li, Y.C., Cheng, T.H., and Gartenberg, M.R. (2001). Establishment of transcriptional
silencing in the absence of DNA replication. Science 291, 650-653.
86
87
Name in Chinese:戚謹文Name in English:Chi, Chin-Wen
Education:Ph.D., State University of New York at Buffalo, NY, USA, (1986)
Affiliation:Institute of Pharmacology, School of Medicine, National Yang Ming University
Title:Professor and Chairman
Tel:886-2-2826-7313
Fax:886-2-2821-3874
E-mail:[email protected]
Field of Specialty:Tumor biology, steroid hormone and receptors, experimental therapeutics
Research Description:
1. The function of steroid hormones and their receptors in cancer tissues
Steroid hormone receptors are cellular signal transducers. Steroid hormones regulate gene
expression via specific steroid hormone receptors. It has been found that the levels of steroid
hormone receptors in tumors were significantly from those of the adjacent normal tissues including
hepatoma, breast cancer, gastric cancer and brain tumors. Steroids and their receptors have multiple
functions in tumors, including regulation of oncogene expression, secretion of tumor markers,
synthesis of proteases, cell growth and angiogenesis. Therefore, the function of steroid hormones
and their receptors is worthy of further investigation.
2. Using rodent hepatoma and gastric tumor model for analysis of Chinese herbal drugs and other
agents.
In vivo tumor models can be generated by tumor cell transplant or by chemical carcinogen
induction. In our laboratory, we have successfully established rodent hepatoma models using
intrasplenic transplant of hepatoma cells. In addition, in situ injection of gastric tumor cells into
stomach of SCID mice generated gastric tumor. These in vivo tumor models will be used for future
analysis of Chinese herbal drugs and other therapeutic agents.
3. Analysis of oxidative stress and changes in free radicals in cancer tissues
In normal cells, the intracellular oxidation and reduction status as well as the electron transport
88
process are maintained in a balanced state. Recently, it has been found that the levels of oxidative
stress and the levels of free radicals were higher in cancer tissues than in normal tissues. Drugs
may modulate the intracellular oxidative stress, calcium signaling and induce apoptosis. The
function of mitochondria, oxidative stress and free radicals in the regulation of tumor growth will
be explored.
Selected Recent publication:1. Chau G.-Y., Wu C.-W., Lui W.-Y., Chang T.-J., Kao H.-L., Wu L.-H., King K.-L., Loong C.-C.,
Hsai C.-Y., and Chi C.-W. (2000) Serum interleukin 10 but not interleukin 6 related with clinical
outcome in patients with resectable hepatocellular carcinoma. Ann Surg 231:552-558.
2. Lin H.-L., Liu T.-Y., Chau G.-Y., Lui W.-Y., and Chi C.-W. (2000) Comparison of 2-
methoxyestradiol, docetaxel and paclitaxel induced apoptosis in hepatoma cells and its relation to
reactive oxygen species. Cancer 89: 983-994.
3. Chen J.-H., Liu T.-Y., Wu C.-W., and Chi C.-W. (2001) Nonsteroidal anti-inflammatory drugs
for treatment of advanced gastric cancer: cyclooxygenase-2 is involved in hepatocyte growth
factor mediated tumor development and progression. Medical Hypothesis 57: 503-505.
4. Lin H.-L., Liu T-Y, Wu C.-W., Chi C.-W. (2001) 2-Methoxyestradiol-induced caspase-3
activation and apoptosis occurs via G2/M arrest-dependent and -independent pathways in human
gastric cancer cells. Cancer 92: 500-509.
5. Lui W.-Y., Chi C.-W., Chang Y.-F., Chu H.-W., Hsieh C.-C., Yin P.-H., Liu T.-Y., Ou Y.-R., and
P’eng F.-K. (2002) In vivo and in vitro growth stimulation of murine hepatoma cells by
glucocorticoid. Anticancer Research 22: 1413-1422.
6. Wang J.-J., Chern Y.-T., Chang Y.-F., Liu T.-Y., and Chi C.-W. (2002) Dimethyladmantyl-
maleimide induced in vitro and in vivo growth inhibition of human colon cancer Colo205 cells.
Anticancer Drugs 13: 533-543.
7. Lin H.-L, WY Lui W.-Y., TY Liu T.-Y., Chi C.-W. (2003) Reversal of Taxol-resistance in
hepatoma by cyclosporin A : involvement of the PI-3 kinase-AKT 1 pathway. British J Cancer
88:973-980.
89
Name in Chinese:姜安娜Name in English:An-Na Chiang
Education:Ph.D. National Taiwan Univ. (College of Medicine)
Affiliation:Institute of Biochemistry, National Yang-Ming University
Title: Professor
Tel:886-2-2826-7122
Fax:886-2-2826-4843
My Personal Homepage:http://www.ym.edu.tw/bio/intro.htm
E-mail:[email protected]
Fields of Specialty:Cardiovascular Biology/Nutritional Biochemistry/ Lipidology
Research Description:
The major interest of our laboratory is the study of endogenous (physiological) and exogenous
(dietary) factors that may protect human from developing atherosclerosis. The basic underlying cause
of atherosclerosis is LDL peroxidation within intravascular cells. We previously found that
apolipoprotein H (apoH, also known as 2-glycoprotein I, 2-GPI) may inhibit LDL oxidation and lipid
accumulation in macrophages. Our recent study has also implicated that 2-GPI protects macrophages
and human coronary artery smooth muscle cells against apoptosis. Due to the interindividual
variability of 2-GPI expression in subjects with various metabolic syndrome and disease states, we
gain more insight into the control of 2-GPI gene regulation by cloning and characterization of 2-GPI
gene promoter in the human hepatocytes. Moreover, the regulation of 2-GPI expression under
oxidative stress is under investigation both at transcription and translation levels.
We are also working on a series of studies to identify the dietary components effective in inhibiting
LDL oxidation. A recent line of our study delineated the relationships among n-3 polyunsaturated fatty
acids (n-3 PUFAs), peroxisome proliferators-activated receptors (PPARs), and atherogenesis. The
cardioprotective effects of n-3 PUFAs come from their hypolipidemic, anti-thrombotic, anti-
inflammatory, and anti-arrhythmic functions. Recent literature indicates that PUFAs may play as the
activators of PPARs. PPARs are known as nuclear transcriptional factors, which may exert overall
inhibitory actions on the processes in atherosclerotic lesion development. We have recently elucidated
how PUFA-regulated PPARs contribute to their target gene expression and lipid homeostasis.
Moreover, we have investigated the effect of herbal medicines on the clearance of cellular lipids via
the regulation of PPARα or PPARγ expression. We have established vascular cell model (macrophages
90
and smooth muscle cells) and atherosclerotic animal model (apoE-knock out mice) for exploring the
control of progression and regression of atherosclerosis. Understanding how PUFAs and herbal
medicines regulate the activity and abundance of PPARs will likely provide insight into the
development of novel therapeutic strategies for better management of atherosclerosis.
Selected Recent Publication:1. Wang HH, Hung TM, Wei J, and Chiang AN. (2004) Fish oil increases antioxidant enzyme
activities in macrophages and reduces atherosclerotic lesions in apoE-knockout mice. Cardiovas.
Res. 61:169-176.
2. Chiang AN , Kou TC, and Wang HH. (2003) Influence of polyunsaturated fatty acids on the
expression of PPARr in vascular cells and their effect on gene transcription. Atherosclerosis
4:216.
3. Lin, K.Y., Chen, Y. L., Shih, C.C., Pan, J.P., Chen, W.E., and Chiang, A.N.(2002)The
contribution of HDL-apolipoproteins to the inhibtion of low density lipoprotein oxidation and
lipid accumulation in macrophages. J. Cell. Biochem. 86: 258-267.
4. Ju-Pin Pan, Shiau-Ting Lai, Shu-Chiung Chiang, Shiu-Chin Chou, and Chiang, A.N.
(2002)The risk of coronary artery disease in population of Taiwan is associated with cys-ser
311 polymorphism of human paraoxonase (PON)-2 gene. Chin. Med. J. 65: 415-421.
91
Name in Chinese:賈愛華Name in English:Eileen Jea Chien
Education:Albert Einstein College of Medicine, New York, USA. Ph.D.
Affiliation:Department of Physiology, School of Medicine, National Yang-Ming University
Title:Associate Professor
Tel:886-2-2826-7088
Fax:886-2-2826-4049
E-mail:[email protected]
Fields of Specialty:Cell Physiology
Research Description: 1. Effect of lipopolysaccharide (LPS) on human peripheral T cells.
2. Nongenomic effect of progesterone on human peripheral T cells.
Selected Recent Publication:1. Chen JJ, Chien EJ , and Wang PS. Progesterone attenuates the inhibitory effects of cardiotonic
digitalis on pregnenolone production in rat luteal cells. J. Cell Biochem. 86:107-117, 2002
2. Chien EJ , Hsieh DJ, and Wang J. The response of alkalinization or acidification by
phytohemagglutinin is dependent on the activity of protein kinase C in human peripheral T cell. J.
Cell Biochem. 81:604-612, 2001.
3. Chien EJ , Chien CH, Chen JJ, Wang SW and Hsieh DJ. Bacterial lipopolysaccharide activates
protein kinase C, but not intracellular calcium elevation, in human peripherial T cells. J. Cell
Biochem. 76:404-410, 2000
92
Name in Chinese:周德盈Name in English:Teh-Ying Chou
Education:M.D., Yang-Ming University School of Medicine, 1984
Ph.D., Biochemistry, Johns Hopkins University School of Medicine, 1995
Affiliation:Yang-Ming University/Veterans General Hospital-Taipei
Title:Associate Professor of Pathology and Biochemistry
Tel:886-2-2875-7449 ext 212
Fax:886-2-2875-7056
My Personal Homepage:http://my.so-net.net.tw/tehying/index.html
E-mail:[email protected]
Fields of Specialty:Thoracic Pathology / Tumor Metastasis
Research Description:Our long-term research goal is to develop methodology for prevention, early detection and
suppression of cancer metastasis. We intend to achieve this goal through the identification and
characterization of metastasis-associated genes using pulmonary adenocarcinoma as a model system.
Selected Recent Publication:1. Small GW, Chou TY, Dang CV, and Orlowski RZ. Evidence for involvement of calpain in c-Myc
proteolysis in vivo. Archives of Biochemistry and Biophysics 400:151-161, 2002
2. Chou TY and Hart GW. O-linked N-acetylglucosamine and cancer. The Molecular Immunology of
Complex Carbohydrates-II, edited by Albert M. Wu. Plenum Press-New York, 2001
93
Name in Chinese:范明基Name in English:Ming-Ji Fann
Education:California Institute of Technology, Ph. D.
Affiliation:Department of Life Sciences
Title:Associate Professor
Tel:886-2-2826-7184
Fax:886-2-2820-0259
My Personal Homepage:http://www.dls.ym.edu.tw/t9.htm
E-mail:[email protected]
Fields of Specialty:Molecular and cellular neuroscience
Research Description:Three intertwined research directions in the laboratory
The first direction is to find novel protein kinases whose expression is differentially in the
developing nervous system and to analyze their roles during the development of the nervous system.
As protein kinases are known to participate in forming many neural characteristics, including neural
connection, transmitter and channel expression, and cognition, I believe this research could have
potentials to unravel puzzles in the development of the nervous system. By using degenerate primer-
based reverse transcription-polymerase chain reaction, we had demonstrated the expression profile of
protein kinases in cultured neurons. From an extension of this study, we identified a novel nuclear
CDC2-like, and arginine/serine (RS)-rich protein kinase from embryonic day 14 (E14) rat cortex.
Northern and western analyses indicated that it is present mainly in brain. The immunofluorescent
staining of postnatal day 14 (P14) hippocampus showed its expression is likely in postmitotic neurons.
As this kinase contains RS domain, we suspected that it could phosphorylate SR proteins that are a
family of nuclear phosphoproteins involved in constitutive and alternative splicing. Evidence shows
that activities of SR proteins, including their subcellular localization, interaction among various SR
proteins, and assembly of functional spliceosome, are controlled by phosphorylation. Thus, we named
this kinase as protein kinase for spliceosome components (PKSC). In cellular level, PKSC is
colocalized with SC35 in nuclear speckles. We also demonstrated that PKSC is a SR protein kinase by
its ability to phosphorylate SR proteins in an in vitro assay. Analyses from sequence profiles,
subcellular localization, and functional assay suggested that PKSC is a novel type of SR protein
kinases. The highly specialized and developmentally regulated expression pattern of PKSC implicates
94
that it may be involved in the generation of diversity of neuronal genes by regulating alternative
splicing patterns, which in turn forms the basis of a variety of neuronal phenotype. We are currently
using transgenic mouse approach to test this possibility.
The second research direction is to search for surface molecules that may function in early neural
development and could use as stem cell markers. By subtractive hybridization, we had found a novel
member of immunoglobulin family whose expression is very abundant in the E10.5 neural tube but
gradually disappears after E12. We named this gene as Shian-Dan (SD). Using P19 cell line as a
neural differentiation model we demonstrated that the expression of this gene was quickly suppressed
when cell differentiate into neurons under influence of retinoic acid. We suspect that this gene is
expressed in neural progenitor cells, and was down-regulated when cells entered into differentiated
status. More over, we used yeast two hybrid assay and have identified several molecules that bind to
the extracellular domain of SD and function as ligands of SD. We intend to pursue further by setting
up a tissue culture system to test whether these ligands activate SD and what effects of activation of
SD are in term of proliferation and differentiation of neural cells.
The third research direction is to search ways that may help neural regeneration in retinal ganglion
cells. This is a collaborative project with Dr. An-Guor Wang, an ophthalmologist in General Veteran
Hospital (Taipei). As a first step, we used subtractive hybridization to find molecules whose levels of
expression change after optic nerve injury. An expression profile database was thus established. Using
RT-PCR and histochemical staining, we demonstrated that cytochrome oxidase is upregulated in the
early phase after injury. We had published two papers to report these findings.
Selected Recent Publication:
1. Wang, A.-G., Lee, C.-M., Wang, Y.-C., Lin, C.-H., and Fann, M.-J. (2002). Upregulation of cytochrome oxidase in the retina following optic nerve injury. Exp. Eye Res. 74, 651-659.
95
Name in Chinese:謝世良Name in English:Shie-Liang Hsieh
Education: Ph.D. University of Oxford, UK (1989-1992)
Affiliation:Institute of Microbiology and Immunology National Yang-Ming University Taipei,
Taiwan
Title:Professor
Tel:886-2-2826-7161
Fax:886-2-2827-7933
My Personal Homepage:http://www.ym.edu.tw/imi/SLHsieh.html
E-mail:[email protected]
Fields of Specialty:Immunology Cancer Biology
Research Description:1. Signaling of human lymphotoxin-beta and HVEM receptors
2. Reverse Signaling of TNF-like molecules triggered by decoy receptor 3 (DcR3) and
osteoprotegrin (OPG)
3. Dendritic-cells based gene therapy for cancers
4. Interaction between TNF superfamily and stem cells
5. Functional genomics approaches for the identification of novel tyrosine kinases in cancer patients
and death-domain containing genes
Selected Recent Publication:
1. Hsu, P.N., Lin, H.H., Chen, N.J., Wu, K.M., Tu, C.F., Tsai, H.F. and Hsieh, SL (2001) *
Human FasL gene does not induce inflammation in pancreas but is unable to protect islet
graft from transplantation rejection in pancreas-specific hFasL transgeneic mice. J. Bio.
Sci, 8, 262-269
2. Chou, A, Lin, LL, Tsai, HF, Hsieh, SL, Hsu, PI and Hsu, PN (2001) Enhanced
proliferation and increased interferon-g production in T cells by signal transduced
through TRAIL. J. Immunology, 167, p1347-1352
3. Chow KP, Lu HC, Chou HF, Liu HP, Hsieh SL, Chang YS, Choo KB. (2002) Induction
of chemosensitivity in nasopharyngeal carcinoma cells using a human papillomavirus
regulatory sequence and the thymidine kinase gene. J Biomed Sci.;9:41-6.
4. Hung, S. C., Chen, N. J., Hsieh, S. L., Li, H., Ma, H. Li., Lo., WH (2002).Isolation and
characterization of size-sieved stem cells from human bone marrow. Stem Cells, 20,
96
p249-258
5. Hsu, T.L., Chang, Y.C., Chen, S.R., Chen, S.R.. Liu Y.C., Chiu, A.W., Chio, C.C., Chen,
L. Hsieh, S.L.* (2002) Modulation of Dendritic Cell Differentiation and Maturation by
Decoy Receptor 3 (DcR3). J. Immunology 168, 4846-4853
6. Chang, Y.H., Hsieh, S.L., Chen, M.C., Lin, W.W. (2002) Lymphotoxin-beta Receptor
Induces Interleukin 8 Gene Expression via NF-kB and AP-1 Activation. Exp. Cell Res.
278, 166-174
7. Chen MC, Hwang MJ, Chou YC, Chen WH, Cheng G, Nakano H, Luh TY, Mai SC,
Hsieh, S.L.* (2003) The Role of ASK1 in Lymphotoxin-beta Receptor-Mediated Cell
Death J. Biol. Chem., 278, 16073-16081
8. Hsu, MJ, Lin, W.W., Tsao, W.C., Hsu, T.L., Chang, Y.C., Chiu, A.W., Chio, C.C., and
Hsieh, S.L.* (2004) Enhanced Adhesion of Monocytes via Reverse Signaling Triggered
by Decoy Receptor 3 (DcR3), Exp. Cell Res. (in press)
9. Yung-Chi Chang,Tsui-Ling Hsu, Hsi-Hsien Lin, Chung-Ching Chio, Allen W. Chiu,
Nien-Jung Chen, Chi-Hung Lin, and Hsieh, S.L.* (2004) Modulation of Macrophage
Differentiation and Activation by Decoy Receptor 3. J. Leuk.Biol., (in press)
10. Shu-Fen Wu, Tan-Mei Liu, Yu-Chun Lin, Huey-Kang Sytwu*, Hsueh-Fen Juan, Shui-
Tein Chen, Kuo-Liang Shen, Sheng-Chuan Hsi, and Hsieh,S.L.* (2004)
Immunomodulatory effect of decoy receptor 3 on the differentiation and function of
bone marrow-derived dendritic cells in nonobese diabetic mice: from regulatory: From
regulatory mechanism to clinical implicationJ. Leuk.Biol. (in press)
11. Yang, C.R., Hsieh, S.L., Su, W.L., Teng, C.M., Lin, W.W (2004) Soluble decoy receptor
3 (DcR3) induces angiogenesis by neutralization of TL1A, a cytokine belonging to TNF
superfamily and exhibiting angiostatic action. Cancer Research (in press)
97
Name in Chinese:徐明達Name in English:Ming-Ta Hsu
Education:P h .D. California Institute of Technology
Affiliation:National Yang Ming University
Title:professor
Tel:886-2-2826-7230
Fax:886-2-2826-4843
E-mail:[email protected]
Fields of Specialty:epigenomic analysis、DNA replication、cancer biology
Research Description:Comprehensive analysis of cis-regulator sequences in specific tissues and in
breast cancer
Selected Recent Publication:
1. Jong Yj, Li LH, Tsou MH, Chen YJ, Cheng SH, Wang-Wuu S, Tsai SF, Chen CM, Huang AT, Hsu
MT, and Lin CH.(2003)
Chromosomal CGH abnormalities in early and late onset human breast cancers: correlations with
disease progression and p53 mutations. Cancer Genetics and Cytogenetics (in press)
2. Chen YJ., Chen, PJ,Lee MC,Yeh SH,Hsu MT,Lin CH.(2002)
Chromosomal analysis of hepatic adenoma and focal nodular hyperplasia by comparative
genomic hybridization Genes Chromosome Cancer35:138-43
3. Lin SC, ChenYJ,kaoSY,HsuMT,LinCH,YangSC,LiuTY.(2002).
Chromosomal changes in betal-associated oral squamous cell carcinomas and their relationship
to clinical parameters.Oral Oncol.266-73
4. YangYC,ShyongWY,ChangMS,ChenYJ,LinCH,HuangZD,Wang,
HsuMT,ChenML.(2002)Frequent gain of copy number on the long arm of chromosome 3in
human cervical adenocarcinoma.Cancer Genet.Cytogent.131:48-53
5. ShannYJ,HsuMT.Cloning and characterization of liver-specific isoform of Chkl gene from rat.
(2001)J.Biol.Chem.276;48863-70
6. ChenYJ,YehSH,ChenJT,WuCC,HsuMT,TsaiSF,ChenPJ,LinCH.(2000)
Chromosomal Changes and clonality relationship between primary and recurrent hepatocellular
98
carcinoma.Gasteroenterology119:431-40
7. Chen PH, Tseng WB, ChuY, Hsu MT(2000)Interference of the simian virus40 origin of
replication by the cytomegalovirus immediate early gene enhancer: evidence for competition of
active regulatory chromatin conformation in single domain. Mol. Cell. Biol 20:4062-4074
99
Name in Chinese:洪善鈴Name in English:Shan-Ling Hung
Education:Ph. D. Molecular Biology Graduate Group, Program in Microbiology, University of
Pennsylvania, PA, U. S. A.
Affiliation:Institute of Oral Biology, National Yang-Ming University
Title:Professor
Tel:886-2-2826-7224
Fax:886-2-2826-4053
My Personal Homepage:none
E-mail:[email protected]
Fields of Specialty:molecular biology, microbiology and immunology
Research Description:
The overall goal of Dr. Hung’s research is to understand the functions of viral proteins, viral entry
and pathogenesis, and the relationship between microbiology and immunology and oral diseases. Two
main areas of current research are as followed:
(A) The pathogenesis of herpes simplex virus: Herpes simplex virus types 1 and 2 (HSV-1 and
HSV-2), producing primary and reactivation infections, are the causative agents of human diseases,
including gingivostomatitis, pharyngitis, herpes labialis, encephalitis, eye and genital infection. The
understanding of viral pathogenesis will help eliminate the viruses and may reduce the diseases caused
by viral infection. The research topics include: (1) the mechanisms involved in complement evasion of
herpes simplex viruses; (2) the interaction of viral glycoproteins and cellular receptors and the possible
signal transduction pathway involved during viral infection into cells of oral origin; and (3) the
possible correlation of herpesvirus infection and periodontal diseases.
(B) The effects of areca quid chewing on microbiology and immunology: Areca
chewing is associated with an increased risk of oral squamous cell carcinoma and
oral submucous fibrosis. Studies have also shown a higher prevalence of
periodontal disease among areca chewers than non-areca chewers. Effects on the
functions of immune cells may be one possible mechanism by which areca quid
chewing compromises the oral health. The research topics include: (1) the effects
of components of areca quid on oral microbiology and periodontal tissues, and (2)
100
the molecular and functional relationship between immune system and areca-
quid associated oral carcinogenesis.
Selected Recent Publication:1. Ling L-J, Hung S-L, Tseng S-C, Chen Y-T, Chi L-Y, Wu K-M, Lai Y-L. Association between
betel quid chewing, periodontal status and periodontal pathogens. Oral Microbiology and
Immunology 2001; 16: 364-369
2. Hung S-L (corresponding author) , Wang Y-H, Chen H-W, Lee P-L, Chen Y-T. Analysis of herpes
simplex virus entering into cells of oral origin. Virus Research 2002; 86: 59-69 (SCI).
3. Hung S-L (corresponding author) , Cheng Y-Y, Wang Y-H, Chang K-W, Chen Y-T. Expression
and roles of herpesvirus entry mediators A and C in cells of oral origin. Oral Microbiology and
Immunology 2002; 17: 215-223
4. Hung S-L , Lin Y-W, Wang Y-H, Chen Y-T, Su C-Y, Ling L-J. Permeability of Streptococcus
mutans and Actinobacillus actinomycetemcomitans through guided tissue regeneration
membranes and their effects on attachment of periodontal ligament cells. Journal of
Periodontology 2002; 73(8): 843-851
5. Hung S-L (corresponding author) , Chen Y-L, Chen Y-T. Effects of safrole on the defensive
functions of human neutrophils. Journal of Periodontal Research 2003; 38(2): 130-134
6. Chen Y-T, Wang Y-H, Cheng Y-Y, Hung S-L (corresponding author) . Direct binding of herpes
simplex virus type 1 virions to complement C3. Viral Immunology 2003; 16(3): 347-355
7. Chen Y-T, Hung S-L, Lin L-W, Chi L-Y, Ling L-J. Attachment of periodontal ligament cells on
chlorhexidine-loaded guided tissue regeneration membranes. Journal of Periodontology 2003;
74(11): 1652-1659
8. Ling L-J, Ho C-C, Wu C-Y, Chen Y-T, Hung S-L (corresponding author). Association between
human herpesviruses and the severity of periodontitis. Journal of Periodontology 2004
(accepted)
101
Name in Chinese:黃正仲
Name in English:Jeng-Jong Hwang
Education:1990 Ph.D. Radiological Health Sciences, Colorado State University, Fort Collins,
Colorado, U.S.A.
Affiliation: Institute of Radiological Sciences
Title:Professor
Tel:886-2-2826-7064
Fax:886-2-2820-1095
My personal homepage:www.ym.edu.tw/rad/taecher/jj.htm
E-mail:[email protected]
Fields of specialty: radiobiology, tumor biology, cell biology, gene/molecular imaging
Research description:
1. Molecular characterization of HPRT gene mutation lesion spectrum in human
nasopharygeal carcinoma cells.
2. Molecular characterization of HPRT gene mutation lesion spectrum in patients with
nasopharygeal carcinoma before and after radiotherapy.
3. Dose-rate effect of ionizing radiation effect on HPRT gene mutation frequency and
lesion spectrum.
4. Study on pharmacokinetics and therapeutic effects of boron-containing lipiodol with
boron neutron capture irradiation in rat hepatoma and normal tissues. I
5. Study on pharmacokinetics and therapeutic effects of boron-containing lipiodol with
boron neutron capture irradiation in rat hepatoma and normal tissues. II
6. The study of in vivo biodistribution and autoradiography of [I-123]-ADAM and its
derivatives: a serotonin transporter binding agent
7. PET gene probe core: sub-project 3- Cell and tissue gene probe imaging core.
8. The study of the relationship between TGF-1 and radiation hepatitis.
9. Study of the change of plasma TGF-beta1 levels in NPC patients before and after
concurrent chemoradiotherapy.
10. The study of quantification and fusion of autoradiography and microPET.
Selected recent publication (Hwang JJ*-corresponding author):
102
1. Wang HE, Liao AH, Deng WP, Chang PF, Chen FD, Liu RS, Chen JC, Lee JS, Hwang JJ (2004):
Evaluation of 4-borono-2-[18F]fluoro-L-phenylalanine-fructose as a probe for BNCT in glioma-
bearing rat model. J Nucl Med, 45, 302-308.
2. Ye XX, Chen JC, Liu RS, Wey SP, Lee JS, Ting G, Hwang JJ* (2004): Microautoraduography of
[123I]ADAM in mice treated with fluoxetine and serotonin reuptake inhibitors. Nucl Med Biol,
(in press)
3. Ye XX, Hwang JJ, Shieh JF, Chen JC (2004). In Vivo Quantification of bound [123I]ADAM to
serotonin transporters in the brains of rabbits by SPECT. Nucl Med Biol, (in press).
4. Deng WP, Yang WK, Lai WF, Liu RS, Hwang JJ, Yang DM, Fu YK, Wang HE (2004): A new
simplified method of preparation and radiolabeling of FIAU for in vivo imaging of herpes
simplex virus type 1 thymidine kinase gene expression. Eu J Nucl Med, 31, 99-109.
5. Lin KJ, Yen TC, Wey SP, Hwang JJ, Ye XX, Tzen KY, Chen JC (2004): Characterization of the
binding sites for 123I-ADAM and the relationship to the serotonin transporter in rat and mouse
brains using quantitative autoradiography. J Nucl Med, (in press).
103
Name in Chinese:高 閬 仙Name in English:Lung-Sen Kao
Education:Ph.D. , University of Massachusetts, Amherst
Affiliation:Faculty of Life Sciences , National Yang-Ming University
Title:Professor
Tel:886-2-2826-7268
Fax:886-2-2823-4898
E-mail:[email protected]
Fields of Specialty:Neurochemistry, Cell Biology
Research Description:1. Regulation of intracellular calcium and neurotransmitter release
2. Molecular mechanism of dopaminergic neuron degeneration
Selected Recent Publication:
1. Pan, C.-Y., Chu, Y.-S. and Kao, L.-S. (1998) Molecular study of the Na+/Ca2+ exchanger in bovine
adrenal chromaffin cells. Biochem. J. 336, 305-310.
2. Yang, D.-M. and Kao, L.-S. (2001) Relative contribution of Na+/Ca2+ exchanger, mitochondria,
and endoplasmic reticulum in the regulation of cytosolic Ca2+ and catecholamine secretion of
bovine adrenal chromaffin cells. J. Neurochem. 76, 210-216.
3. Liu, P.-S., Liaw, C.-T., Lin, M.-K., Shin, S.-H., Lin, L.-F., and Kao, L.-S. (2003) Amphetamine
enhances Ca2+ entry and catecholamine release via nicotinic receptors activation in bovine adrenal
chromaffin cells Eur. J. Pharmacol. 460, 9-17.
4. Lo, H.-S., Chiang, H.-C., Lin, Anya , M. Y., Chiang, H.-Y., Chu, Y.-C. and Kao, L.-S. (2004)
Synergistic effects of dopamine and Zn2+ on the induction of PC12 cell death and dopamine
depletion in the striatum: possible implication in the pathogenesis of Parkinson's disease.
Neurobiol. Dis. In press
104
105
Name in Chinese:李德章Name in English:Te-Chang Lee
Education:Ph. D. in Biochemistry, National Taiwan University
Affiliation:Institute of Biopharmaceutical Science, National Yang-Ming University
Title:Vice president / professor
Tel:886-2-2826-7200
Fax:886-2-2820-1886
My Personal Homepage:E-mail:[email protected]
Fields of Specialty:Biochemistry, Toxicogenomics, Cancer Biology
Research Description:Chronic exposure to arsenic continues to be a severe toxicological and pathological problem in
humans. Epidemiological evidence strongly supports that chronic arsenic exposure is accompanied by
increased risks for cancers and vascular disorders. We are currently focusing on the following two
projects:
1. Arsenic-induced alteration of gene expression profiling: Recently developed colorimetric cDNA
micrarray technique is adopted to investigate the effects of arsenic exposure on gene expression
profile. We have collected several hundreds of plasmids with gene fragments involved in signaling
pathways, transcription factors, protein kinases and phosphatases, oncogenes, tumor suppressor
genes, DNA repair, and cellular defense, etc. Microarray membranes will then be prepared for
elucidating the genetic or epigenetic alterations involved in arsenic-induced stress response and
neoplastic transformation.
2. Molecular mechanisms underlying which arsenic triggers the initiative of atherosclerotic lesion
106
progression: Since phenotypic modulation of VSMC resulting intimal migration and accelerated
proliferation is critical in the onset of atherosclerotic lesions, knowing how arsenic modulates
VSMC proliferation is of fundamental importance to understand early events in the formation of
these critical lesions. Therefore, we would like to ask whether exposure of quiescent VSMC to
arsenite at a low dose range modulates the profiling of gene expression and whether the modulated
gene expression profiling influences the responsiveness of VSMC to endogenously and
exogenously growth promoting factors.
Selected Recent Publication:1. Yih LH and Lee TC (2003) Induction of c-anaphase and diplochromosome through
dysregulation of spindle assembly checkpoint by sodium arsenite in human fibroblasts.
Cancer Res., 63: 6680-6688.
2. Yih LH, Peck K, Lee TC (2002) Changes in gene expression profiles of human
fibroblasts in response to sodium arsenite treatment. Carcinogenesis, 23: 867-876.
3. Yih LH and Lee TC (2000) Arsenite induces p53 accumulation through an ATM-
dependent pathway in human fibroblasts. Cancer Res., 60: 6346-6352
4. Huang SC, Huang CY and Lee TC (2000) Induction of mitosis-mediated apoptosis by
sodium arsenite in HeLa S3 cells. Biochem. Pharmacol., 60:771-780.
5. Ho IC, Yih LH, Kao CY and Lee TC (2000) Tin-protoprophyrin potentiates arsenite-
induced DNA strand breaks, chromatid breaks and kinetochore-negative micronuclei in
human fibroblasts. Mutat. Res., 452: 41-50.
6. Yih LH and Lee TC (1999) Effects of exposure protocols on induction of kinetochore-
plus and -minus micronuclei by arsenite in diploid human fibroblasts. Mutat. Res., 440:
75-82.
7. Huang SC and Lee TC (1998) Arsenite inhibits mitotic division and perturbs spindle
dynamics in HeLa S3 cells. Carcinogenesis, 19: 889-896.
107
Name in Chinese:吳妍華
Name in English:Yan-Hwa Wu Lee
Education:B.S. Department of Agronomy (1966-1967)
Department of Agricultural Chemistry (1967-1970)
National Taiwan University M.S. Institute of Biochemistry, School of MedicineNational Taiwan University (1970-1972)Ph.D. Department of Biochemistry University of Tennessee, U.S.A. (1972-1976)
Affiliation:Institute of Biochemistry, National Yang-Ming University
Title:President/Professor, National Yang-Ming University
Tel:886-2-2826-7124, 886-2-2826-7001
Fax:886-2-2826-4843, 886-2-2825-0936
My Personal Homepage:http://www.ym.edu.tw/bio/teacher/wyh.htm
E-mail:[email protected]
Fields of Specialty:Biochemistry, Molecular Biology, Molecular Virology
Research Description:Virus often targets critical regulatory events in host cells. The effects of viruses on the host cells
can be mediated by addition of virus-specific macromolecules to a cellular complex. Alternatively, the
virus may cause a disassembly of a host-cell complex, or lead to the assembly of a new infected cell-
specific complex. Thus, knowledge of the processes subverted by viruses has often highlighted the
mechanisms of viral pathogenesis. The main goal of our study is to elaborate the types of interactions
between hepatitis virus-encoded macromolecules and the host cells, which may define the ultimate
outcome of a virus infection.
108
Selected Recent Publication:
1. Yeh, T.S., and Lee, Y.H.W. (1998). Assembly of hepatitis delta virus particles: package of
multimeric HDV genomic RNA and role of phosphorylation. Virology 249, 12-20.
2. You, L.R., Chen, C.M., and Lee, Y.H.W. (1999). The hepatitis C virus core protein modulates the
NF-kB signal pathway triggering by lymphotoxin-b receptor ligands and tumor necrosis factor-
a. J. Virology 73, 1672-1681.
3. You, L.R., Chen, C.M., Yeh, T.S., Tsai, T.Y., Mai, R.T., Lin, C.H., and Lee , Y.H.W. (1999).
Hepatitis C virus core protein interacts with cellular putative RNA helicase. J. Virology 73, 2841-
2853.
4. Chung, Y.L., Lee, Y.H.W. , Yen, S.H., and Chi, K.W. (2000). A novel approach for nasopharyngeal
carcinoma treatment uses phenylbutyrate as a protein kinase c modulator: implications for
radiosensitization and EBV-targeted theraphy. Clin. Cancer Res. 6, 1452-1458.
5. Huang, W.H. Yung, B.Y.M., Syu, W.J., and Lee, Y.H.W. (2001). The nucleolar phosphoprotein
B23 interacts with hepatitis delta antigen and modulates the hepatitis delta virus RNA replication.
J. Biol. Chem. 276, 25166-25175.
6. Chen, S.Y., Kao, C.F., Chen, C.M., Shih, C.M., Hsu, M.J., Chao, C.H. C., Wang, S.H., You, L.R.,
and Lee, Y.H.W. (2003). Mechanisms for inhibition of hepatitis B virus gene expression and
replication by hepatitis C virus core protein. J. Biol. Chem. 78, 591-607.
7. Kao, C.F., Chen, S.Y., Chen, J.Y., Lee, Y.H.W. (2004) Modulation of p53 transcription regulatory
activity and posttranslational modification by hepatitis C virus core protein. Oncogene 23, 2472-
2483.
8. Kao, C.F., Chen, S.Y., Lee, Y.H.W. (2004) Activation of RNA polymerase I transcription by
hepatitis C virus core protein. J. Biomed. Sci.11, 72-94.
109
Name in Chinese:林姝君Name in English:Shu-Chun Lin
Education:1987, B.S. in Zoology, National Taiwan University.
1989, M.S. in Microbiology and Immunology, National Yang-Ming University.
1995, Ph.D. in Biochemistry, University of Illinois at Chicago, USA
Affiliation:Institute of Oral Biology, National Yang-Ming University
Title:Associate Professor
Tel:886-2-2826-7272
Fax:886-2-2826-4053
My Personal Homepage:http://www.ym.edu.tw/iob
E-mail:[email protected]
Fields of Specialty:Tumor Biology/Molecular Biology/Molecular Pathology
Research Description:Studying the molecular mechanisms of areca (betel)-associated oral pathogenesis is my major
research interest. My recent studies also focus on insighting the cellular and molecular impacts of
IGFBP-5 on oral keratinocytes.
Selected Recent Publication:1. Lin SC *, Liu CJ, Chiu CP, Chang SM, Lu SY and Chen YJ (2004) Establishment of OC3 oral
carcinoma cell Line and identification of NF-κB activation responses to areca nut extract. J Oral
Pathol Med 33: 79-86.
2. Lin SC, Chung MY, Huang JW, Shieh TM, Liu CJ and Chang KW* (2004, In press) Correlation
between genotype in matrix metalloproteinase-1 (MMP-1) gene promoter and the risk of oral
squamous cell carcinomas. J Oral Pathol Med.
3. Lin SC , Lo SS, Chung MY, Liu CJ and Chang KW* (2004) Functional matrix metalloproteinase-
2 (MMP-2) genotype and the risk of oral squamous cell carcinomas. J Oral Pathol Med. (In
press)
4. Lew TS, Chang CS, Fang KP, Chen CY, Cheng CH and Lin SC* (2004) The involvement of
Kv3.4 voltage-gated potassium channel in the growth of an oral squamous cell carcinoma cell
line. J Oral Pathol Med. (In press)
110
5. Chang KW, Yuan TC, Fang KP, Yang FS, Chang CS, and Lin SC* (2003) Over expression of
voltage-gated potassium channel Kv3.4 in oral squamous carcinoma. J Oral Pathol Med 32: 606-
11.
6. Lin SC , Wang CP, Chen YM, Lu SY, Fann MJ, Liu CJ, Kao SY, Chang KW* (2002) Regulation
of IGFBP-5 expression during tumourigenesis and differentiation of oral keratinocytes. J Pathol
198: 317-25.
7. Chang, KW, Kao, SY, Tzeng RJ, Liu, CJ, Cheng AJ, Wong, YK, Yang SC and Lin SC* (2002)
Multiple molecular alterations of FHIT in betel-associated oral squamous cell carcinoma. J
Pathol 196: 300-6.
8. Lin SC , Chen YJ, Hsu MD, Chang CS, Liu TY, Lin CH and Chang KW* (2002) The
chromosomal changes of oral squamous cell carcinoma associated with betel quid use. Oral
Oncol 38: 266-73.
9. Lin SC, Chang KW, Chang CS, Tzeng YS, Yang FS, Liu TY and Wong YK* (2000) p16/MTS1
alterations in oral squamous cell carcinomas from Taiwanese - correlated with tumor progression.
J Oral Pathol Med 29: 159-66.
111
Name in Chinese:許萬枝Name in Engligh:Wan-Jr Syu
Education: Ph.D. University of Wisconsin-Madison, USA
Affiliation: Institute of Microbiology and Immunology
Title: Professor
Tel: 02-2826-7112; 2826-7003
Fax: 02-2821-2880
My Personal Homepage: http://www.ym.edu.tw/imi/WJSyu.html
E-mail: [email protected]
Field of Specialty: Host-pathogen interaction; pathogenicity of microbes; immunochemistry
Research Description:
Characterization of viral or bacterial pathogenicity using molecular, immunochemical and genomic
approaches; natural products that have antimicrobial or cytotoxic activities and their functional
mechanism
Selected Recent Publications:
1. Hsu SC, Wu JC, Sheen IJ, Syu WJ (2004) Interaction and replication activation of
genotype I and II hepatitis delta antigens. J Virol. 78, 2693-2700.
2. Huang YH, Wu JC, Hsu SC, Syu WJ (2003) Varied immunity generated in mice by DNA
vaccines with large and small hepatitis delta antigens. J Virol. 77, 12980-12985.
3. Chiu HJ, Lin WS, Syu WJ (2003) Type III secretion of EspB in enterohemorrhagic Escherichia
coli O157:H7. Arch Microbiol. 180, 218-26.
4. Wu CF, Wang SH, Sun CM, Hu ST, Syu WJ (2003) Activation of Dengue Protease Autocleavage
at the NS2B-NS3 Junction by Recombinant NS3 and GST-NS2B Fusion Proteins. Journal of
Virological Methods 114, 45-54.
5. Hsu SC, Syu WJ, Sheen IJ, Liu HT, Jen KS, Wu JC. (2002) Different effiencies of viral assembly
and RNA editing of genotypes I and II hepatitis D viruses. Hepatology 35, 665-674.
6. Wang SH, Syu WJ, Huang KJ, Lei HY, Yao CW, King CC, Hu ST. (2002) Intracellular
localization and determination of a nuclear localization signal of the core protein of dengue virus.
J Gen Virol. 83, 3093-102.
112
7. Syu WJ, Don MJ, Ou JC, Lee GH, and Sun CM. (2001) Cytotoxic and novel compounds from
Solanum indicum. J. Natural Products 64, 1232-1233.
8. Liao CP and Syu WJ. (2002) Analysis of the baseplate region of phage AR1 that specifically
infects Escherichia coli O157:H7. J Micobiol Immunol Infect 35, 269-271.
9. Yu SL, Ko KL, Chen CS, Chang YC, and Syu WJ. (2000) Characterization of the distal tail fiber
locus and determination of the receptor for phage AR1 that specifically infects E. coli O157:H7.
J. Bacteriol. 182, 5962-5968.
10. Lin HP, Hsu SC, Wu JC, Sheen IJ, Yan BS, and Syu WJ. (1999) Localization of isoprenylated
antigen of hepatitis delta virus by anti-farnesyl antibodies. J. Gen. Virol. 80, 91-96.
113
Name in Chinese:蔡世峰Name in English:Shih-Feng Tsai
Education:M.D., Taipei Medical College, 1981.
Ph.D., Mt. Sinai School of Medicine, CUNY, 1987
Affiliation:National Health Research Institutesm, National Yang-Ming University
Title:Director, Professor
Tel:886-2-2652-4120
Fax:886-2-2789-0484
My Personal Homepage:http://www.nhri.org.tw/nhri_org/mm/main1_1.htm
E-mail:[email protected]
Fields of Specialty:Genomics, Human Genetics, Molecular Medicine
Research Description:1. Human Genetics. Modern genetic technology has been used to identify the molecular
mechanism underlying Mendelian traits and complex traits. Recently we succeeded in isolating
disease gene for an autosomal dominant form of osteonecrosis (avascular necrosis of femoral
head).
2. Cancer Genomics. Re-sequencing strategy was applied to identify genomic features that
distinguish cancer tissues from normal controls. A major focus is on identifying mechanism of
loss of tumor suppressor gene function in the chromosome 4q region in liver cancer.
3. Microbial Genomics. Large-scale sequencing was conducted at the genome level of five
bacteria. We are particularly interested in studying two human pathogens: V. vulnificus and K.
pneumoniae.
4. Comparative Genomics. We have taken a comparative approach to analyze the genomic
organization and regulation of alcohol dehydrogenase gene complex. Genomic sequences have
been colleted for human, mouse, and chimpanzee, and help identify unique features for the
evolution and regulation of this important enzyme.
Selected Recent Publication:1. Fan FF, Shen HH, Tseng WP, Chen PM, & Tsai SF. Molecular cloning and
characterization of a human brain-specific gene implicated in neuronal differentiation.
(1998) Molecular Brain Research 54: 113-123.
2. Tsou AP, Wu KM, Tseng TI, Chi CW, Chiu JW, Lui WY, Hu CP, Chang C, Chou,CK, &
114
Tsai SF. Parallel hybridization analysis of multiple protein kinase genes: identification
of gene expression patterns characteristic of human hepatocellular carcinoma. (1998)
Genomics 50: 331-340.
3. Shen HH, Huang AM, Hoheisel J, & Tsai SF. Identification and characterization of a
SET/NAP protein encoded by the brain-specific gene, MB20. (2001) Genomics 71(1):
21-33.
4. Fujiyama A, Watanabe H, Toyoda A, Taylor TD, Itoh T, Tsai SF, Park HS, Yaspo ML,
Lehrach H, Chen Z, Fu G, Saitou N, Osoegawa K, de Jong PJ, Suto Y, Hattori M, &
Sakaki Y. Construction and analysis of the first human-chimpanzee comparative clone
map. (2002) Science 295:131-134.
5. Chen CY, Wu KM, Chang YC, Chang C-H, Tsai HC, Liao TL, Liu YM, Chen HJ, Shen
Arthur BT, Li JC, Su TL, Shao CP, Lee CT, Hor LI, & Tsai SF. Comparative genome
analysis of Vibrio vulnificus, a marine pathogen. Genome Research 13(12):2577-2578
6. Liu MT *, Su JS *, Huang CY, Tsai SF. Novel Mutations Involving the NF1 Gene
Coding Sequence in Neurofibromatosis Type 1 Patients from Taiwan. J. Hu
Genet.2003;48(10) :545-549
7. Ling-Hui Li, Jian-Chiuan Li, Yung-Feng Lin, Chung-Yen Lin, Chung-Yung Chen and
Shih-Feng Tsai.Genoomic shotun array: a procedure linking large-scale DNA
sequencing witg regional transcript mapping. Nucleic Acids Research, 2004, Vol. 32,
No. 3 e27
8. Chang YT, Shiao YM, Chin PJ, Liu YL, Chou FC, Wu S, Lin YF, Li LH, Lin MW, Liu
HN, and TSAU SF. Genetic polymorphisms of the HCR gene and a genomic segment in
close proximity to HLA-C are associated with psoriasis patients in Taiwan (2003)Br.
J. Dermatol.(in press)
115
Name in Chinese 陳芬芳Name in English:Fung-Fang Wang
Education:Ph. D, Dept. of Chemistry, Indiana University, USA
Affiliation:Institute of Biochemistry, National Yang-Ming University.
Title:Professor
Tel:886-2-2826-7126
Fax:886-2-2826-4843
E-mail:[email protected]
Fields of Specialty:Tumor biology, signal transduction, gene regulation
Research description:Our laboratory is working on the molecular mechanisms of p53 action. p53 tumor suppressor
functions as a guardian of the genome that plays an important role in suppressing cancer development,
and mutation on the p53 gene ranks as the most common genetic events in human cancers. A large
body of evidence indicates that p53 is required for maintaining the integrity of the genome under
environmental stresses. p53 is a transcription factor, central to the action of this tumor suppressor is its
ability to activate specific genes carrying distinct p53 binding motif. We have isolated two novel p53
target genes, THTR-1 and DDA3, and are currently studying the function and regulation of their
encoded proteins using cell culture systems as well as mouse model.
Publications:1. Chuang, C.C., Tan, S.K., Tai, L.K., Hsin, J.P. and Wang, F.F. (1998) Evidence for the
involvement of protein kinase C in the inhibition of prolactin gene expression by
transforming growth factor-2. Mol. Pharmacol. 53, 1054-1061.
2. Jang, Y.C., Kao, L.S. and Wang, F.F. (1998) Involvement of Ca2+ signaling in the
vasoactive intestinal peptide and 8-Br-cAMP induction of c-fos mRNA expression.
Cell. Signal. 10, 27-34.
3. Lo, P.K., Chen, J.Y., Lo, W.C., Chen, B.F., Hsin, J.P., Tang, P.P. and Wang, F.F. (1999)
Identification of a novel mouse p53 target gene DDA3. Oncogene 18, 7765-7774
4. Tang, P.P. and Wang, F.F. (2000) Induction of IW32 erythroleukemia cell differentiation
by p53 is dependent on protein tyrosine phosphatase. Leukemia 14, 1292-1300.
116
5. Lo. P.K., Chen, J.Y., Tang, P.P., Lin, J., Lin, C.H., Su, L.T., Wu, C.H., Chen, T.L., Yang,
Y. and Wang, F.F. (2001) Identification of a mouse thiamine transporter gene as a direct
transcriptional target for p53. J. Biol. Chem. 276, 37186-37193.
6. Lo, P.K. and Wang, F.F. (2002) Identification of transcriptional start sites and splicing
of mouse thiamine transporter gene, THTR-1. Biochem. Biophys. Acta.1576, 209-213.
7. Hsieh, S.C., Lo, P.K. and Wang, F.F. (2002) DDA3 is a direct transcriptional target gene
of p53 and p73. Oncogene 21, 3050-3057.
8. Tang, P.P., Hsieh, S.C. and Wang F. F. (2002) Modulation of caspase activation and
p27Kip1 degradation in the p53 induced apoptosis in IW32 erythroleukemia cells. Cell.
Signal. 14, 961-968.
9. Lo, P. K. and Wang F. F. (2004) 5’–heterogeneity of mouse Dda3 transcripts is
attributed to differential initiation of transcription and alternative splicing. Arch.
Biochem. Biophys. (in press)
117
Name in Chinese:魏耀揮Name in English:Yau-Huei Wei
Education:Ph.D. in Biochemistry, Department of Chemistry, State University of New York at
Albany, New York, USA
Affiliation:Institute of Biochemistry, National Yang-Ming University
Title:Professor
Tel:886-2-2826-7118
Fax:886-2-2826-4843
E-mail:[email protected] or [email protected]
Fields of Specialty:Bioenergetics and Biomembranes, Free Radical Biology and Medicine,
Mitochondrial Genetics and Diseases, Molecular Medicine
Research Description:
Mitochondria and sperm have been playing major roles in my research work in the past two
decades. In the last 15 years, my laboratory has been involved in the studies on aging-associated
mitochondrial DNA (mtDNA) mutations and their effect on mitochondrial respiratory function and
production of reactive oxygen species (ROS). We are one of the few laboratories that have
systematically studied mtDNAs with large-scale deletions in different tissues of the aged individuals.
By developing a cybrid system based on cytoplasmic transfer, we have succeeded in delivering
mtDNA with a specific mutation into host cells without mtDNA (called ρo cells) and examine the effect
of certain mtDNA mutation on the phenotype of the cells. On the other hand, we have identified a
number of disease-associated mutations in mtDNA of patients with various mitochondrial diseases.
We have characterized the mutations associated with Leber's hereditary optic neuropathy (LHON),
myoclonic epilepsy and ragged-red fiber disease (MERRF), mitochondrial myopathy, encephalopathy,
lactic acidosis, and stroke-like episodes (MELAS), Kearns-Sayre syndrome (KSS), and Leigh
syndrome. We are currently involved in the construction of more cybrids by re-populating the ρo cells
with mtDNA from each of the patients with a distinct mitochondrial disease. These cybrids have been
used as a model system to investigate the quantitative relationship between mutated mtDNA and
mitochondrial dysfunction and production of ROS in human cells. We wish to gain a better
understanding of the molecular mechanism underlying the pathogenesis of each of the mitochondrial
diseases. The other line of research that we have been engaged is the study on mutations and depletion
of mtDNA in the spermatozoa of males with infertility or subfertility. We have characterized several
118
novel mtDNA deletions in sperm of infertile males. Recently, we found that mtDNA depletion and a
CAG triplet repeat polymorphism in the gene coding for mitochondrial DNA polymerase gamma are
important etiological factors for asthenospermia. The expression of mitochondrial genes in
spermatozoa will be examined with an aim to understand the coordination between mitochondria and
the nucleus in the regulation of sperm function.
Selected Recent Publication:
1. Wei, Y. H., and H. C. Lee (2002) Oxidative stress, mitochondrial DNA mutation and
impairment of antioxidant enzymes in aging. Exp. Biol. Med. 227:671-682.
2. Liu, C. S., H. W. Chen, C. K. Lii, C. S. Tsai, C. L. Kuo, and Y. H. Wei (2002) Alterations
of plasma antioxidants and mitochondrial DNA mutation in hair follicles of smokers. Environ.
Mol. Mutagen. 40:168-174.
3. Wei, Y. H., and H. C. Lee (2003) Mitochondrial DNA mutations and oxidative stress in
mitochondrial diseases. Adv. Clin. Chem. 37:83-128.
4. Lin, P. H., S. H. Lee, C. P. Su, and Y. H. Wei (2003) Oxidative damage to mitochondrial
DNA in atrial muscle of patients with atrial fibrillation. Free Radic. Biol. Med.35:1310-1318.
5. Lu, C. Y., E. K. Wang, H. C. Lee, H. J. Tsay, and Y. H. Wei (2003) Increased expression
of manganese-superoxide dismutase in fibroblasts from patients with CPEO syndrome. Mol.
Genet. Metabol. 80:321-329.
6. Liu, C. S., C. S. Tsai, C. L. Kuo, H. W. Chen, C. K. Lii, Y. S. Ma, and Y. H. Wei (2003)
Oxidative stress-related alteration of the copy number of mitochondrial DNA in human
leukocytes. Free Radic. Res. 37:1307-1317.
7. Kao, S. H., H. T. Chao, H. W. Liu, T. L. Liao, and Y. H. Wei (2004) Sperm mitochondrial
DNA depletion in men with asthenospermia. Fertil. Steril., in press.
119