5th Annual REACH IRACDA Symposium€¦ · Professor, Molecular and Cellular Biology Baylor College...

5th Annual REACH IRACDA SymposiumMay 19th, 2014

10:00am-3:30pm

Keynote Lecture: Chester Brown, MD, PhD

“Effects of TGF-Beta Super-family Signaling on Adipocyte Development and Function”

Posters by IRACDA Fellows and Undergraduate Students

Student Research Talks and Career Panel

AJ Hinton “Estrogen-Responsive Neurons In The Medial Amygdala Prevent Stress-Induced Hypertension”

Berenice Carrilo, PhD “The Influenza A Virus Protein NS1 Displays Structural Polymorphism”

IRACDA MISSION

The mission of the Institutional Research and Academic Career Development Award, IRACDA, is to combine a traditional mentored postdoctoral research experience with an opportunity to develop teaching skills through mentored assignments at a minority-‐serving institution. The program is expected to facilitate the progress postdoctoral candidates toward research and teaching careers in academia. Other goals are to enhance curricula in minority serving institutions by incorporating research topics and active learning, provide a resource to motivate the next generation of scientists at minority-‐serving institutions, and to promote linkages between research-‐intensive institutions and minority-‐serving institutions that can lead to further collaborations in research and training.

FOR MORE INFORMATION, PLEASE VISIT OUR WEBSITE:

http://www.bcm.edu/diversityprograms/iracda

Dr. Gayle Slaughter Senior Associate Dean, Graduate School Professor, Molecular and Cellular Biology

Baylor College of Medicine Principle Investigator of REACH IRACDA Program

Front Cover: Images from left to right attributed to: Dr. Brown, AJ Hinton and Dr. Carrillo

SYMPOSIUM SCHEDULE

10:00 a.m. -‐ 10:30 a.m. Alkek Lobby (1st Floor)

Symposium Registration Breakfast provided by VWR Representative Trent Cullen

10:30 a.m. – 10:45 a.m. Cullen Auditorium

Welcome Graduate School Dean Deborah Johnson, Ph.D.

10:45 a.m. -‐ 11:30 a.m. Cullen Auditorium

Career Development Panel Alejandro Contreras, M.D., Ph.D. (research intensive academics) Diane Scaduto, Ph.D. (biotech research) Danielle Martinez, Ph.D. (tech transfer) Adrianna Visbal, Ph.D. (acedemics)

11:30 a.m. – 12:00 p.m. Cullen Auditorium

Graduate Student Research Talks Berenice Carrillo, Ph.D.

“The influenza A virus protein NS1 displays structural polymorphism” AJ Hinton “Estrogen-‐Responsive Neurons In The Medial Amygdala Prevent Stress-‐Induced Hypertension”

12:00 p.m. -‐ 1:00 p.m. Cullen Auditorium

Keynote Lecture Chester Brown, M.D., Ph.D. “Effects Of TGF-‐Beta Superfamily Signaling On Adipocyte Development And Function”

1:00 p.m. – 2:00 p.m. Rayzour Lounge

Lunch

2:00 p.m. -‐2:45 Alkek Lobby (1st Floor)

Poster Session 1 (Odd numbered posters)

2:45 p.m. -‐3:30 Alkek Lobby (1st Floor)

Poster Session 2 (Even numbered posters)

Dean of Graduate School Deborah Johnson was born in Fort Sill, Oklahoma where her father was stationed in the military. She attended many schools before winning the Bernville Award in Biochemistry and completing a biochemistry major at Albright College in Pennsylvania. She entered graduate school at a time when there were few women in science. More than one faculty member commented that she was too petite and “cute” to be a scientist. Luckily, she didn’t listen to those people and neither did the faculty who accepted her as a PhD student at Georgetown University where she won the Zorbac Award for Outstanding PhD Dissertation. She won an American Cancer Society Fellowship as a post-‐doc at Yale and was promoted to Associate Research Scientist.

Dr. Johnson accepted a position as an Assistant Professor at the University of Southern California (USC) where she progressed to Full Professor. She co-‐founded CoCensys, Inc and applied for a patent for alleviating stress, anxiety and seizure. Her early cancer research was supported by grants from USC, the American Cancer Society, the Margaret E. Early Medical Research Trust, the Wright Foundation, the Elsa U. Pardee Foundation. She received larger grants from the National Cancer Institute of the National Institutes of Health and has published nearly 60 papers. Like most top researchers, Dr. Johnson reviewed grants submitted to the NIH, the National Science Foundation, the Department of Defense, the Qatar National Research Fund and the Wellcome Trust Fund and papers submitted to a number of scientific journals. But Dr. Johnson also cared about education and advised more than a dozen PhD students and post-‐docs and served on many education committees that led to appointments as the director of multiple courses, graduate programs and as Associate Dean of the Graduate School.

Dr. Johnson is a mom, which gave her the perspective to serve on the USC Childcare Committee and establish University daycare. Her husband is a consultant for multiple companies that enabled her to accept BCM’s offer to become our 3rd Dean of the Graduate School and bring her vision that prepares graduate scientists for careers in a variety of areas. She moved her lab, her students and joined the department of Molecular and Cellular Biology as a Professor. As the BRASS Chair of Graduate Education she interacts with members of Houston’s philanthropic community. She even rode a horse in her first Houston Rodeo as a guest of BRASS.

Keynote Lecturer Chester Brown MD/PhD has always been busy. He was an Eagle Scout who won a scholarship to Howard University where he became a MARC Scholar. Now he’s a husband, dad to two active kids involved in Scouts and Little League, a physician, a scientist, a mentor and an active member of a number of education committees that provide guidance to programs and students regarding biomedical science careers. He has been a very successful leader and mentor for BCM’s African American Men in Science group that includes more than 20 post-‐bacs, PhD students, post-‐docs, staff scientists and assistant professors. He provides valuable insight for the Initiative for Maximizing Student Diversity program and the MD/PhD Operating committees.

After Chester received a BS from Howard University in Washington, DC, he entered the MD/PhD program at the University of Cincinnati College of Medicine supported by the Krucker M.D., Ph.D. Fellowship, a NIH MARC Pre-‐doctoral Fellowship and a

Marion Merrell Dow MD/PhD Fellowship. He came to Baylor College of Medicine for a residency in Pediatrics and a fellowship in Medical Genetics. He has become a valued member of the BCM family. He conducted post-‐doctoral research supported by nationally competitive grants like the NIH K08 HD1156, the USPH 2 P30 HD27823, and a grant from the Robert Wood Johnson Foundation. He became an Assistant Professor supported by the Burroughs Wellcome Fund Career Award in the Biomedical Sciences and the March of Dimes Basil O’Connor Starter Scholar Research Award. He was honored with the Excellence in Research Award by the NMRI NIDDK South Regional Workshop. He describes his research on obesity for the SMART undergraduate summer research program each summer and in other seminars. Dr. Brown has already mentored dozens of MDs and PhD students and serves on nearly 30 PhD dissertation committees where he helps students gain the most from their research efforts. His role in contributing to science and mentoring was recognized with the Houston Black MBA Leadership Empowerment Award for Science/Health.

Dr. Brown is a tenured Associate Professor of Molecular and Human Genetics and Pediatrics and also a member of the Translational Biology and Molecular Medicine Graduate Program. He is a co-‐investigator on a major new NIH grant, the Collaborative African Genomics Network that will provide African scientists and physicians with training and equipment to enhance genomics research in Africa. He is a reviewer for a number of scientific journals and has published more than 25 scientific papers. He sees pediatric and adult genetics patients at Texas Children’s Hospital and Ben Taub Clinic, that serves mostly indigent patients. He presents seminars for the general public on topics like sickle cell anemia.

Featured Researchers Berenice Carrillo, Ph.D. attended New Mexico State University in Las Cruces, NM, and graduated with a B.S. in Biochemistry and a minor in Molecular Biology. Despite becoming pregnant during her sophomore year in college, Berenice continued to pursue her dream of becoming a scientist. Obtaining her college degree was not easy, as she was responsible for raising her son as a single parent. She gained access to research through two NIH diversity programs, MBRS-‐RISE and MARC. She cloned and expressed polyamine oxidase (PAO) from avena sativa in S.cerevisiae and helped develop apoptotic assays that aided in elucidating PAO’s role in apoptosis. As an undergrad, she conducted summer research at the Mayo Clinic located in Scottsdale Arizona.

Berenice was accepted by BCM’s Department of Molecular Virology and Microbiology, as a single parent. She received her Ph.D. in 2013, mentored by Dr. VBD Prasad, after successfully cloning, expressing, purifying and determining the X-‐ray crystal structures of wildtype and a mutant form of the NS1 protein of influenza A virus. Her structural data provided information that could aid in understanding how NS1 functions and in developing antiviral drugs against NS1.

Berenice won a 1st place talk award and a 3rd place poster award at MVM research retreats, a 2nd place poster award at the BCM Graduate Student Research Symposium, received an honorable mention award for a talk at the Biochemistry and Molecular Biology Retreat and a travel award to give an oral presentation for the American Society for Virology conference. She published one first author paper, co-‐authored another paper and co-‐wrote a book chapter that reviewed NS1 structure and function.

Like a number of BCM students, Berenice developed close ties to Houston through co-‐workers, friends and the wonderful man she met here and married. Her son is now a big brother. Luckily, Houston is an important center for structural biology research. BCM is the home to the National Center for Macromolecular Imaging, offering internationally recognized colleagues and state-‐of-‐the art specialty equipment. Structural virology holds the key to developing better vaccines and anti-‐viral agents to prevent or limit diseases that still kill millions of children a year worldwide. As a mother, Dr. Carrillo understands that issue and has chosen to further her career as a molecular virologist working on rotavirus that kills approximately 500,000 children a year. As a post-‐doc in Dr. Prasad’s lab, she will focus on determining the structures of two Rotavirus proteins, NSP3 and VP3, which play an important role in rotavirus replication, pathogenesis and genome packaging.

Antentor, AJ to his friends, Hinton, a 3rd year PhD student is one of Dr. Browns’ mentees. AJ’s mentors have helped him win more awards than any 2nd year student in BCM’s history. As an African American/Native American who grew up in North Carolina, AJ had a passion for learning. He started college at Winston Salem State University (WWSU) with scholarships from the university and two churches and then won another academic scholarship. Winning the Coach’s Award for Varsity Tennis and becoming All-‐Academic in the Mid-‐Atlantic Conference did not keep AJ from also being selected as a MARC Scholar to conduct research at WSSU and at Duke University. AJ is very committed to helping others excel and served as a tutor for several classes and as the President of the Biology Club’s Project Strengthen and the Vice-‐President of the Health Careers Opportunities Program. He graduated Magna Cum Laude, won the Outstanding Leadership Award and was listed in the Who’s Who of US College Students.

Dr. Gayle Slaughter met AJ at an ABRCMS and realized that he had an advanced knowledge of G-‐proteins that are targets for many drugs. When she told him about Dr. Ted Wensel’s award winning work, he applied to enter BCM and was accepted by our NIH funded PREP post-‐bac program. He defined several characteristics of a mouse mutant that developed obesity as a result of knocking-‐out a G-‐protein subunit.

AJ was accepted by multiple PhD programs and decided to accept BCM’s offer, partly because of the excellent mentorship he received from people like Jonathan Respress, a very successful PREP alumnus and BCM IMSD PhD student and other BCM African American men. AJ is studying the role of steroid hormones in how the brain regulates obesity and blood pressure. He has already tied for and won the Best Poster Award from his PhD program (2013, 2014), tied for the best PhD Qualifying Exam Award from the IMBS program, won a 2nd place poster award at the BCM Graduate Student Research Program and the Doris Shockley Best Poster Award given by the FASEB at their national conference. He helped his mentor receive a NIH Diversity Supplement to support his research.

AJ has been a very active President of the Association for Graduate Student Diversity and an excellent lecturer for summer review courses and teaching assistant for the BCM PhD course, Organization of the Cell, leading to an impressive 97% passing rate. His then fiancé, now wife, Kaamilya, helped students visualize cell structures by filling the board with drawings course director Rick Sifers, PhD described as “masterpeices”. Kaamilya is a theater major and psychology minor at Texas Southern University where she won an award for best musical performance in an ensemble.

Science Career Panelists Alejandro Contreras, M.D., Ph.D. is a fitting subject for a heart-‐warming hometown success story. He grew up in Houston in a working class, Hispanic neighborhood that was home to many immigrants, like his parents. His local high school, Milby, was one of the magnet schools created at the suggestion of Houston philanthropist and one of BCM’s first donors Wilhemina Daisy Cullen Robertson. Mrs. Robertson’s family had provided her with an excellent education she thought should be available to more Houston children, so she helped the school system develop schools with special resources. Oil companies donated lab equipment and provided summer jobs to high achieving Milby students. Alejandro excelled at Milby and won a scholarship to attend Harvard. It was a difficult transition to the Ivy Leagues, but he graduated and returned to Houston. Alejandro’s potential was recognized by one of BCM’s top researchers, Jeff Rosen, PhD, who championed his new technicians’ acceptance with a full scholarship to BCM’s MD/PhD program.

Dr. Rosen is a very good talent scout. He and Rafael Herrera, PhD were co-‐mentors for Alejandro’s PhD studies. Alejandro won the Molecular and Cellular Biology Outstanding Academic Achievement Award, received a national fellowship and published four papers on breast cancer research. He won the Deborah K. Martin Award for Outstanding BCM Ph.D. Student and the BCM Alumni Award. As the BCM Ph.D. Student Commencement Speaker, he honored his parents before thousands of graduates, faculty, parents, children and friends.

Dr. Contreras completed the MD/PhD program and then a residency at the University of Chicago Medical Center before returning to BCM for a surgical pathology fellowship and to continue a relationship with a special collaborator he met as a PhD student. Dr. Contreras is currently a BCM Assistant Professor of Pathology who conducts breast cancer research and provides patient care. Dr. Contreras has published 13 cancer research papers, so far. He provides the unique perspective of an alumnus to the IMSD Steering Committee and as an interviewer for the Molecular and Cellular Biology Program and the MD/PhD Program.

Danielle Willis Martinez, Ph.D. heard about BCM’s PREP post-‐bac program when she was a part time technician at BCM her last two years as a biology major/math minor at the University of Houston. Danielle combined her preparation for PhD study with preparing to be a new mom! Her daughter was born soon after she started her PhD studies in the IBMS Program at BCM. She and her husband welcomed a second child in her 2nd year of graduate school. She continued her PREP research as a PhD student under the mentorship of Estella Medrano, PhD, a member of the PREP Steering Committee. Dr Medrano was already a full Professor, an international leader in skin cancer research, wife of a physicist and mother of multiple children. Like her mentor, Danielle quickly developed a reputation as an extremely efficient researcher and very helpful lab mate. She won a travel award from the prestigious Cold Spring Harbor to present a poster on her research on how histone modification modulates transcription and the transformation of melanocytes cancer in China! Danielle was saddened by Dr. Medrano’s tragic death in a traffic accident caused by a speeding car as she returned from a Gordon Conference that had been held in Switzerland. Dr. Nikolas Timchenko became Danielle’s mentor so she could complete her PhD research and publish three papers. Like many of our alumni, Daniele’s marriage linked her to Houston. Houston has become a ‘hot market” for biomedical careers. She had no problem finding further opportunities for her career development as a post-‐doctoral fellow at the University of Texas Health Science Center at Houston (UTHealth). She studied RNA-‐based mechanisms of gene regulation in inflammation. In addition to her research, she served as a Secretary of the Post-‐doctoral Association. PDAs play a major role in helping PhDs understand the wide range of career options for scientists. Biomedical research has yielded incredible advances in basic knowledge that are on the verge of being translated into practical, clinical applications. Bench scientists need help identifying and cultivating their discoveries for use in patients. Organizations have developed internships to allow scientist to “try out” different careers. Dr. Martinez was selected as a Technology Licensing Trainee at UTHealth and impressed her supervisors so much that she was offered a job as a Licensing Assistant. She is responsible for assessing, licensing and commercializing the “intellectual property” generated by the faculty, staff and students at UTHealth. She develops marketing material, drafts, negotiates, processes and monitors confidentiality disclosures of licensing agreements. She has already spearheaded 50 agreements. Dr. Medrano would certainly have been delighted with Dr. Martinez’s role in helping science progress toward offering drugs that can control and cure diseases.

Diane Scaduto, Ph.D. never imagined when she started a chat with Gayle Slaughter, PhD at 10:30 pm at a SACNAS Conference where it would lead. She was an avid volleyball player undergrad at California State Polytechnic with a double major in chemistry and political science and a MPA in public administration. The she received a BS in biochemistry and microbiology at California State university, Los Angeles. When she was accepted to PhD programs and law school, her Hispanic mother wanted her to get an education, her Italian father wanted her to go to law school. But Diane had been accepted by BCM’s PhD program and her visit to Houston and the Cell and Molecular Biology Program had convinced her that Dr. Slaughter’s “sales pitch” had been true. Little did she imagine that her first lab rotation with Michael Metzker, PhD would change the history of law. Diane was asked to prepare DNA for a special sequencing project for which Dr. Metzker had developed a program to track mutations. Her meticulous work led to identifying a man who had intentionally spread HIV to multiple women. The results convinced a Texas jury to sentence Philippe Padieu to 45 years in prison. But it was the courage of the six women that knew he infected them that became the real story. They didn’t hide in embarrassment; they told their story in a one-‐hour 20/20 special, part of which was filmed at BCM. When the producers taping Dr. Metzker, asked to bring the PhD student in, Diane quickly found a clean lab coat. Seeing his daughter on national TV convinced Diane’s dad that scientists play very important roles in law and justice. The infected women were interviewed on the Oprah Show, reaching millions of viewers. Then Law and Order, SVU based a show on the court case. Dr. Metzker went to New York to serve as a consultant and brought Diane back an autographed photo from star Mariska Hargety. Diane joined Dr. Metzker’s lab and was the first author on a Proceedings of the National Academy of Sciences publication describing the cases. Dr. Metzker received a NIH Diversity Supplement to support Diane’s research. She won the Claude W Smith Research Award from the CMB Program (now IBMS Program). Her dissertation project identified sequences in Hispanics that might predispose them to diabetes, which is important to Diane’s Hispanic mother. Diane presented very well received lectures on frontier level sequencing for BCM PhD students, SMART Program undergraduates, students at the University of St. Thomas and students at the DeBakey High School for Health Professions. Dr. Scaduto was conducting post-‐doctoral research on cancer cells and the surrounding stroma at MD Anderson Tumor Hospital and Research Institute, when Applied Diagnostics, Inc decided to recruit an expert in NextGen Sequencing to establish a new facility at their biotech company. Dr. Scaduto was an obvious choice for the knowledgeable leader they needed. She is delighted with her “new toys” and will soon make discoveries to diagnose and treat genetics diseases.

Adrianna Visbal travelled from her native South America to attend Texas A & M University where she majored in Cell and Molecular Biology. Texas A & M students are very well prepared for BCM academic classes as was evident when Adrianna won the Graduate School’s top academic award and then a Department of Defense Breast Cancer Fellowship. She was co-‐mentored by Professor Jeff Rosen, PhD and Assistant Professor Michael Lewis, PhD. Adrianna won a 2nd Place Poster Award at the Graduate Student Research Symposium and then 2 years later was selected by her PhD program as their GSRS speaker. She won 2nd place poster awards at two Breast Cancer Retreats and published six papers. Adrianna also won BCM’s top teaching assistant award for the course widely believed to be the toughest in grad school, Gene Regulation. That award, and her very successful record as a researcher, impressed the Selection Committee who chose her as one 5 post-‐docs for the 2011 IRACDA Program. Dr. Visbal has been an excellent participant as she conducted breast cancer research with Dr. Dean Edwards. She recently taught introductory biology and cancer biology at the University of Houston Downtown. Dr. Visbal is applying for academic positions in Houston, because she is married to fellow career options panelist and BCM Assistant Professor Alejandro Contreras. He participated by himself the first year we sponsored the career options because Dr. Visbal had just given birth to their son. Dr. Visbal will teach GRE prep to SMART Program undergraduates and PREP post-‐bacs this summer, who hopefully will become researchers and professors who are as successful as she has been.

First Year IRACDA Scholars Michael Cato, Ph.D. Jackson State University, MS Graduate School-‐Special Programs Mentor: Shuxing Zhang, Ph.D

Research Interests: in silico structured based drug design, protein dynamics, protein-‐ligand binding, application of chemometric or bioinformatic approaches for the elucidation of the biological profile of small molecules regarding their targets, off-‐targets and phenotypic

outcome, homology modeling, drug discovery and modeling of robust biological systems.

Nina M. Poole, Ph.D. University of Memphis, TN Biology Mentor: Anthony Maresso, Ph.D.

My research project focuses on determining the virulence factors involved in Extraintestinal Pathogenic Escherichia coli (ExPEC) translocation from the gut to distance organs. I am currently utilizing a human Caco-‐2 adenocarcinoma cell line model to screen ExPEC strain

CP9 knockouts that are deficient in adhering, invading, and migrating across the epithelial monolayer. The broader goal and impact of this project is to identify the factors and mechanisms which allow ExPEC to breach the gut epithelium to cause bloodstream and systemic infections in immunocomprised individuals.

Kathleen B. Quast, Ph.D. Harvard University, MA Neuroscience Mentor: Benjamin Arenkiel, Ph.D.

My research focuses on the neural circuitry and excitatory/inhibitory balance within the mammalian olfactory bulb. I use electrophysiology, in vivo calcium imaging and behavior analysis to dissect the contributions of the inhibitory neurons in sensory processing within

the olfactory bulb. In the olfactory bulb continuing neurogenesis continually adds inhibitory granule cells to the circuitry, making the olfactory bulb a unique model of not only sensory processing but adult neurogenesis as well.

Second Year

Denae Rachelle Nash, Ph.D. Baylor College of Medicine, TX Cell and Molecular Biology Mentor: John Swann, Ph.D.

The focus of my research is working to determine the contributions of PI3K/mTOR and Ras/ERK pathway hyperactivation to development, maintenance, and progression of a vascular malformation seen in a rare congenital disorder, Sturge-‐Weber Syndrome. Patients

with these intracranial vascular malformations also have devastating neurological comorbidities, including early onset epilepsy, hemiparesis, and mental retardation. These neurological symptoms are a consequence of reduced function of the overlying vasculature malformation, and by identifying the molecular pathways contributing to development and maintenance of the malformations, new targets for treatment, some of which are already available for cancer therapy, will provide clinicians with additional treatment tools and strategies.

Deborah Ritter, Ph.D. Boston College, Chestnut Hill, MA -‐ Biology Human Genome Sequencing Center, Molecular and Human Genetics Mentor: David A. Wheeler, Ph.D.

My research involves identifying genomic anomalies in cancer by using genome sequencing data, as well as identifying germline predisposing genes in familial cancer syndromes and inherited cancers, using pediatric familial sequencing data. I am focusing on discovering

conserved noncoding regions (enhancers) that may regulate gene expression, and the deletion/insertion/ translocation events that move or obviate these regions in relation to cancer and inherited cancer syndromes.

Sara J. Wright, Ph.D. University of California, CA Biochemistry & Molecular Biology Mentor: Theodore Wensel, Ph.D.

I am interested in determining the molecular mechanisms that regulate light-‐stimulated responses of retinal ON-‐bipolar cells, which are secondary neuronal cells that sense the release of glutamate from photoreceptor cells in the retina. This pathway is regulated by

the Regulator of G protein signaling (RGS) proteins RGS7 and RGS11, and possibly by the orphan GPCR, GPR179. I would like to determine the role of GPR179 in this pathway, and to identify RGS7 interacting proteins and determine their possible roles in RGS7 localization and stability.

Luz E. Vela, Ph.D. University of Houston-‐Main Campus -‐ Biochemistry Mentor: Anthony Maresso, Ph.D.

My post-‐doctoral work focuses on establishing a 3-‐dimensional model of the intestinal system. By colonizing this model with infectious bacteria, we will be able to better study host-‐pathogen interactions. We have already shown, in mice, an infection can be harbored for up to six days in these “mini” guts. An advantage to our model is the five cell types found

in the enteroids as oppose to single cell type in most cultures used today. Our expectation is that this model will serve other investigators as an alternative to the in-‐vivo experiment.

Second Year continued

Third Year Marco D. Giles, Ph.D. Baylor College of Medicine, TX Pharmacology Mentor: Jin Wang, Ph.D.

My postdoctoral research involves the synthesis of dendritic macromolecules for the encapsulation and selective delivery of anti-‐cancer therapeutics. The dendrimer is constructed with completely biodegradable and biocompatible

glycerol and N-‐acetylcysteine as a means of producing a potentially non-‐cytotoxic drug vehicle.

Edward Nam, Ph.D. Vanderbilt University, TN Cancer Biology Mentor: Gad Shaulsky, Ph.D.

I study how the single-‐celled amoeba, Dictyostelium discoideum, feeds on bacteria, including the human pathogenic bacteria Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Legionella pneumophila. A major goal is to identify

immune-‐like proteins involved in this process.

Michael Toneff, Ph.D. Baylor College of Medicine Molecular and Cellular Biology Mentor: Jeffrey Rosen, Ph.D.

My post-‐doctoral work focuses on the study of epithelial to mesenchymal transition (EMT) in mammary gland development and breast cancer. EMT has been linked to a stem cell-‐like phenotype and is associated with resistance to cancer therapies. We have developed and

validated EMT sensors and a micro-‐RNA sensor that can identify cells displaying an EMT to facilitate the identification of putative EMT/stem cells in mouse models as well as to identify chemical inhibitors of EMT in high throughput screening assays.

Elizabeth Salisbury, Ph.D. Baylor College of Medicine, TX Translational Biology and Molecular Medicine Mentor: Alan Davis, Ph.D. My postdoctoral research is focused on investigating two distinct populations of progenitor cells associated with the peripheral nerves that contribute to heterotopic, or abnormal, bone formation within the soft tissues. One of these populations gives rise to brown

adipocyte-‐like cells that are critical for generating the microenvironment necessary for bone formation. The other population directly generates the cells responsible for creating bone.

2012 Shivas Amin, Ph.D. Tenure Track Assistant Professor University of Saint Thomas, Houston, TX Audrea Burns, Ph.D. Asst. Dir. Of Regulatory Affairs for Pediatrics Human Immunology Texas Children’s Hospital/BCM, Houston, TX Maria Fadri-‐Moskwik, Ph.D. Instructor Washington State University, Pullman, WA Timothy Montminy, Ph.D. Lecturer University of New Hampshire, Durham, NH Ryan Udan, Ph.D. Post-‐doctoral Fellow Baylor College of Medicine, Houston, TX Tenure Track Assistant Professor Missouri State Univ (8/1/2014)

2011 Charletha Irvin-‐Wilson, Ph.D. Senior Research Analyst – Dept. of Pediatrics: Hematology: Oncology Cell and Gene Therapy Baylor College of Medicine, Houston, TX Albert Ribes-‐Zamora, Ph.D. Tenure-‐track Assistant Professor Department of Biology University of Saint Thomas, Houston, TX Hector Sandoval, Ph.D. Postdoctoral Associate Department of Genetics Baylor College of Medicine, Houston, TX Melissa Suter, Ph.D. Postdoctoral Associate Department of Obstetrics & Gynecology Baylor College of Medicine, Houston, TX Gregory Dement, Ph.D. Director, Center for Excellence in Learning and Teaching University of Houston-‐Downtown, Houston, TX

2013 Fredy D. Reyes, Ph.D. Research Associate Rutgers University, Rutgers, NJ Aaron Lauver, Ph.D. Adjunct Instructor Lone Star College, Houston, TX Michael H Grider, Ph.D. Visiting Assistant Professor Haverford College, Haverford, PA Gabriel J. Villares, Ph.D. Instructor Rice University, Houston, TX Timothy Mahoney, Ph.D. MBA student Rice University, Houston, TX Adriana Visbal, Ph.D. Post-‐doctoral Associate Baylor College of Medicine, Houston, TX

REACH IRACDA Fellow Alumni

New Courses Developed by REACH IRACDA Fellows Biophysics (Prairie View A&M University), Team led by Maria Fadri-‐Moskwik, Ph.D. and Ryan Udan, Ph.D. Biophysics (University of Houston-‐Downtown), Freddy Reyes, Ph.D. Cancer Biology (University of Houston-‐Downtown), Melissa Suter, Ph.D. Molecular Techniques (University of St. Thomas), Albert Ribes-‐Zamora, Ph.D. Neuroscience (University of Houston-‐Downtown), Michael Grider, Ph.D.

REACH IRACDA Courses

Selected Courses Taught by REACH IRACDA Fellows Anatomy and Physiology I Lab (BIOL 2045) Fall 2013; University of St. Thomas Elizabeth Salisbury, Ph.D. COURSE DESCRIPTION: This course is the laboratory companion to BIOL 2445. Students will engage in hands-‐on activities to enhance their understanding of the major organ systems (integumentary, skeletal, muscular, and nervous) discussed in the first semester of the anatomy and physiology lecture course. These systems will be explored in depth at both the cellular/ tissue level through histological examination and at the gross anatomic level through dissections and the analysis of various models.

Molecular Biology (BIOL 4330) Fall 2011, University of Houston-‐Downtown Maria Fadri-‐Moskwik, Ph.D. COURSE DESCRIPTION: Molecular Biology serves as an introduction to the molecular aspects of gene regulation in eukaryotic cells. The course emphasizes study of the primary research literature and the creation and testing of hypotheses using current technology. (adapted from the BIOL 4330 course description by Dr. Akif Uzman, Dean of the College of Science and Technology at UHD) At the end of the course, students will demonstrate the abilities to: (1) recall and articulate the mechanisms of synthesis, repair, and regulation of DNA, RNA, and protein, (2) design an experiment to isolate biological molecules of interest based upon a desired testable hypothesis, (3) successfully perform biochemical calculations related to molecular biology, (4) apply knowledge and understanding of molecular biology to draw conclusions from experimental data, and (5) describe and recognize analytical strategies to manipulate the flow of biological information. Molecular Techniques (BIO 4393) Spring 2012, University of St. Thomas Timothy Mahoney, Ph.D., and Gabe Villares Ph.D. COURSE DESCRIPTION: This course is designed as an introduction to understanding and performing key molecular biology techniques in the context of a real laboratory experiment utilizing C. elegans as a model system. Students will acquire the skills to perform basic molecular biology techniques as well as obtain experience in scientific writing, critical analysis of a scientific problem, and working as a team.

Organic Chemistry I (CHEM 2033) Spring 2013, Prairie View A&M University Marco Giles, Ph.D. COURSE DESCRIPTION: For chemistry majors, minors, chemical engineering, and science majors. Electronic structure and bonding, introduction to organic compounds, reactions of alkenes, stereochemistry, reactions of alkynes, electron delocalization and resonance, reaction of dienes and elimination reactions.

Special Topics: Cancer Biology (BIOL 3390) 2013, University of Houston Downtown Adriana Visbal, Ph.D. COURSE DESCRIPTION: This course will review the basic principles of cancer biology at the cellular and molecular level expanding on previous cell biology and genetics knowledge. The student will learn how basic cellular processes are disrupted in cancer and explore the contributing factors to these disruptions. Using breast cancer as a model disease, the course will also provide a brief overview of diagnosis, treatment, and cancer prevention and how they are intimately tied with basic and clinical research. A seminar series by experts in the breast cancer field will allow students to directly interact with experienced professionals and understand the interplay between research and treatment. Additionally, the course will employ popular literature to discuss the historical and ethical aspects of cancer research. Required Reading: Principles of Cancer Biology by Lewis J. Kleinsmith (Pearson Benjamin Cummings); The Emperor of All Maladies: A Biography of Cancer by Siddhartha Mukherjee.

Selected Courses Taught by REACH IRACDA Fellows continued Introduction to Biophysics and Biomedical Imaging (BIOL 4163/PHYS 4163) Spring 2012, Prairie View A&M University Ryan Udan, Ph.D., Maria Fadri-‐Moskwik Ph.D., and Fredy Reyes, Ph.D. COURSE DESCRIPTION: This course is designed to provide students with the required foundation for understanding the principles of biophysics and their application in the biological sciences and medical applications. The course will prepare the students to utilize elementary concepts of modern biophysics and to appreciate problems in the current biomedicine and biomedical research. Students will demonstrate understanding of the contributions of biology, physics, and engineering to the interdisciplinary field of biomedical imaging. Topics to be covered include: The fundamentals of digital image acquisition and processing, optical, confocal and fluorescence microscopy, membrane biophysics, x-‐ray imaging, ultrasound, and magnetic resonance imaging.

Microbiology (MBIO 2305) Fall 2011, The University of Houston-‐Downtown Audrea Burns, Ph.D. COURSE DESCRIPTION: There are three major themes within the course: understanding the structure and function of microbes, mechanisms of containing and killing microbes and highlighting common diseases caused by microbes. Throughout the course, the instructor will communicate the basic principles of microbiology. Students will be taught the function, morphology, basic physiology (metabolism and replication), and classes of bacteria. Further, students will learn how and what bacteria cause common human diseases and the immune response to infection. We will discuss exciting new research on microbial interactions and the immune response. Further, through lecture, discussions, oral and written presentations as apart of the final project, students will have the opportunity to gain a thorough appreciation of the complexity of microorganisms.

Developmental Biology/Developmental Biology lab (BIOL 3445) Fall 2011 (Course developed, but not offered), University of St. Thomas Ryan Udan, Ph.D. COURSE DESCRIPTION: A study of how organisms develop from a single cell to an adult. Two themes to the course will be discussed: classical developmental biology and modern topics in developmental biology. The goals of the course are to provide students with 1) a strong foundation in the basic and modern principles of developmental biology, 2) the ability to fluently describe the developmental signaling pathways, and their roles in specific cellular events that relate to development or disease, 3) techniques to study and manipulate different model organisms from selected phyla which contribute to a deeper understanding of how organisms develop, 4) the ability to integrate and reinforce different levels of biology (genetics, molecular and cellular biology, physiology, ecology and evolution, cancer and stem cell biology) to contribute to the understanding of how organisms form.

Genetics Laboratory Spring 2011, University of St. Thomas Timothy Mahoney, Ph.D. (co-‐taught) COURSE DESCRIPTION: Helped to develop a new genetics lab using C. elegans and Drosophila, along with some modules on genetic variation testing and bioinformatics. This is the third introductory course in the biology department; therefore, the goal is to prepare students in basic molecular techniques and genetics. Emphasis is placed on mastering laboratory skills, though future versions of the course will place more emphasis on merging these topics to an overall problem or case study.

Selected Courses Taught by REACH IRACDA Fellows continued General Microbiology (BIOL 3333) Fall 2011, University of St. Thomas Timothy Montminy, Ph.D. COURSE DESCRIPTION: General Microbiology serves as an introduction to the biology of microorganisms with an emphasis of prokaryote biology. Major topics include bacterial cell structure and function, bacterial growth and metabolism, microbial genetics, and the control of microbial growth. Course work, examinations, and classroom activities are problem based, stressing data interpretation and critical thinking skills. At the completion of the course students will be able to: 1) describe the morphology, culture, movement, and biochemical activities of a variety of microorganisms, 2) understand various structure-‐function relationships in both bacteria and viruses, 3) explain the process by which bacteria replicate, repair, and transfer their genetic material 4) discuss mechanisms of gene regulation common in bacteria, and 5) interpret experimental data involving techniques commonly used in microbiology.

Molecular Biology (BIOL 3351) Spring 2012, University of St. Thomas Timothy Montminy, Ph.D. COURSE DESCRIPTION: The Molecular Biology course is designed to introduce the molecular basis of biological activity and the molecular techniques utilized to study biology. A special focus is placed on the interactions of DNA, RNA and protein biosynthesis in eukaryotic biology. Course work and class activities involve a variety of problem solving exercises, emphasizing the interpretation of primary data and experimental design. At the completion of the course students will be able to: 1) describe the general principles of gene and genome organization, genome replication, and gene expression, 2) understand the processes of transcription and translation and how both are regulated, 3) discuss the basic elements of protein folding, sorting, and modification, 4) explain the basics of gene regulation and protein function, and 5) interpret the outcome of experiments that involve common molecular biology techniques.

Bioinformatics (BIOL 3310) Spring 2011 and 2012, University of St. Thomas Shivas Amin, Ph.D. COURSE DESCRIPTION: Bioinformatics is the capstone course for all students with a major in Bioinformatics. The course exposes students to current research, literature and techniques in the field of Bioinformatics. Throughout the semester students must develop an original Bioinformatics project that they must present at the end of the class. Upon completion of the course students should be able to 1) Evaluate and compare bioinformatic tools 2) Retrieve relevant data from databases and 3) Develop and test hypothesis using bioinformatic techniques.

Introduction to Population Biology and Evolution (BIOL 1351) Fall 2011, University of St. Thomas Shivas Amin, Ph.D. COURSE DESCRIPTION: This course is the first semester of Introduction to Biology. This course exposes students to the theory of evolution, patterns of inheritance, genetics, ecology, and species diversity. In previous years, this course was typically taught in the second semester. During the summer of 2011, I worked with UST faculty to redesign the introduction to biology courses and practicum so that students are first exposed to the unifying theories of biology prior to an introduction to biomolecules, genes and cellular processes.

Introduction to Biology Practicum (BIOL 1151) Fall 2011, University of St. Thomas Shivas Amin, Ph.D. COURSE DESCRIPTION: The practicum is the laboratory component of the BIOL1351 course. The practicum introduces students to basic biological techniques and principals as well as enhances their comprehension of scientific literacy. A constant focus of this course is the proper present of scientific material. Students worked in groups to complete activities that strengthens their understanding of topics taught to them in BIOL1351, read scientific literature, performed basic biological experiments and produce scientific reports and posters.

Selected Courses Taught by REACH IRACDA Fellows continued Evolution (BIOL 4332) Spring 2012,University of St. Thomas Shivas Amin, Ph.D COURSE DESCRIPTION: Evolution is the capstone course for all students with a major in Biology. This course presents various aspects of the theory of evolution from historical, philosophical and research based perspectives. The course is taught in discussion based format and student participation and debate is the main activity. Additionally, students are also required to read and present landmark papers relevant to the theory of evolution.

Neuroscience Spring 2012, The University of Houston-‐Downtown Michael Grider, Ph.D. COURSE DESCRIPTION: Offered to upper-‐level biology students, my class is designed to cover the basics of neuroscience while incorporating ideas from each level of analysis…”from molecules to mind”. For example, the students have learned the complex molecular steps involved in the ‘firing’ of a neuron, how the connections of many neurons form a system (e.g. visual system), and how systems work together at the organismal level to affect behavior, mood, and motivation. I have incorporated several didactic techniques to promote learning. The class incorporates active learning, encouraging students to work together to solve a problem then present their conclusions to their fellow students. “Clicker” technology permitted instant feedback and participation by the students. In addition, the students are responsible for knowing not only the facts, but also about the landmark research experiments behind these important facts. This encourages students to think like a scientist and provides real-‐world examples of how scientific discoveries are made. I incorporated interesting subject matter aimed at younger students, as well. For example, we covered drugs of abuse in the reward system, sexual desire in the hypothalamus, ADHD, etc. I feel that the combination of interesting subject matter, group based active learning, frequent quizzes/feedback, and presentation of original research has allowed my students to explore the field of neuroscience and peak their curiosity, while reinforcing the basics they will need in future science courses. Introduction to Cell and Molecular Biology (BIOL 1352) Spring 2013; University of St. Thomas Elizabeth Salisbury, Ph.D. (co-‐taught) COURSE DESCRIPTION: This course is an introduction to the principles and concepts of cellular and molecular biology. Major topics covered include cell structure, metabolism, respiration, photosynthesis, transcription, and translation. Students will explore how it is possible that the cell is the simplest unit of life, but is capable of so many complex functions. In addition, students will learn about the structure of DNA, its replication, and its role in gene expression. Finally, we will cover biotechnology which includes the real-‐world applications of molecular biology used by modern scientists. Upon completion of this course, students should be able to demonstrate understanding of life at both the molecular and cellular levels. Basic Lab Techniques in Biology (BIOL 1152) Spring 2013; University of St. Thomas Elizabeth Salisbury, Ph.D. (co-‐taught) COURSE DESCRIPTION: This course is the laboratory component of BIOL 1352. This practicum introduces students to four major themes: ecosystems, organisms, cells and molecules. Students will gain practical experience in scientific methodology, critical thinking, reading and writing, focusing on analysis of scientific literature through discussion, team based learning and invited research presentations. At the completion of the course students will: 1) be able to apply the tenets of the scientific method in both descriptive and quantitative analyses, 2) develop critical reading and thinking skills through reading and discussions of scientific literature, 3) be able to explain and discuss the latest cutting edge research in the field of biology and articulate an opinion about its relevance and impact to society, 4) develop their oral communication skills through in-‐class presentations and class discussion, 5) be able to apply an ethical approach to the practice of the scientific method.

Selected Education-‐Related Publications and Presentations Fadri, M.*, Udan, R.*, Reyes, F.*, Mitchell, H., Cudnik, B., Regisford, G., and Saganti, S. (2011, June). Promoting

interdisciplinary learning: Instituting an “Introduction to Biophysics and Biomedical Imaging” Course at Prairie View A&M University. Poster Presentation. National IRACDA Symposium. Houston, TX. (*these authors contributed equally to the work)

Fadri, M.*, Udan, R.*, Reyes, F.*, Mitchell, H., Cudnik, B., Regisford, G., and Saganti, S. (2013). Promoting interdisciplinary learning: Instituting an “Introduction to Biophysics and Biomedical Imaging” Course at Prairie View A&M University. Manuscript in preparation. (*these authors contributed equally to the work)

Fadri, M. and Rodgers, JR. (2013). OPTEMA: A tool to teach critical thinking in undergraduate science education. Manuscript in preparation.

Amin, S. (2012, June). Making Protein Structures Come to Life. Oral Presentation. IRACDA National Conference. Philadelphia, PA.

Suter, M. An Educational and Creative Outlet to Prepare the Undergraduate Student for the “GooYouWiki” World. Oral Presentation. IRACDA National Conference.

REACH IRACDA Accomplishments

Methods in Enzymology Molecular Biology Molecular and Cellular Biology Molecular Endocrinology Molecular Human Reproduction Nature Communications Nature Genetics Pediatric Endocrinology Review Pediatric Research PloS Biology PloS Genetics Reproductive Medicine Science Stem Cells Translational Medicine Viruses

American Journal of Obstetrics and Gynecology American Journal of Human Genetics Annual Review of Genetics Cell Clinical Genetics Developmental Biology Developmental Cell Epigenetics FASEB Journal Human Pathology Journal of Cell Biology Journal of L American Journal of Human Genetics eucocyte Biology Metabolism

SMART PREP Program Baylor College of Medicine

Junior-‐Senior Research Seminar University of St. Thomas

UHD-‐Scholars Academy Graduate School Application Seminar Series University of Houston-‐ Series

REACH IRACDA Fellow Participation In Mentoring Programs PVAMU Research Scholars Journal Club: BCM Postdoctoral Association Journal Club Series Prairie View A&M University

Neuroscience Lab (485) Rice University

Selected Conferences Attended by REACH IRACDA Fellows 2013 IRACDA National Conference, Atlanta, GA

2012 IRACDA National Conference, Philadelphia, PA 2011 IRACDA National Conference, Houston, TX

Southwest and Gulf Coast Regional Society for Developmental Biology, Austin, TX Weinstein Cardio-‐vascular Development Conference, Chicago, IL

Association for Research in Vision and Ophthalmology, Ft. Lauderdale, FL

The Biology of Genomes, Cold Spring Harbor Laboratories, NY American Society of Clinical Oncology, Chicago, IL

REACH IRACDA Fellow Teaching Strategies and Techniques Class discussions: small group discussions to review concepts, analyze data, and propose experiments.

Clickers: each student is able to respond simultaneously using handheld electronic response systems, which promotes student competition and allows instructors to immediately gauge student engagement and comprehension.

Electronic/Social media: implemented in numerous approaches for engaging students. Importantly, students are enthusiastic about using these alternative approaches to gather, analyze, and share data.

Gallery walk: A method of diagramming course concepts and discussing them.

GEOSET video presentations: 10-‐minute videos on scientific topics, this is an international site for informal science education.

Graduate school workshops: multi-‐session workshops with guidance tips on applying for graduate school in the sciences (PVAMU, UHD). Houston wide Graduate School Application Workshops presented 2011-‐12 with 60-‐70 attendees.

Incorporating scientific literature review and discussion in class: Integration of primary literature into the curriculum by assigning papers to students for outside reading and in class discussion, which can include the instructors doctoral research.

Jeopardy quiz games: teams of students compete to answer "Jeopardy" style questions as a method of reviewing course material.

Journal clubs: assigned papers were discussed, usually with advanced (PVAMU) or MARC students (UHD). PVAMU journal club was started by IRACDA fellows, but is now an official activity of the BCM Post-‐doc Association.

MATLab calculations: Students were introduced to the MatLab program to facilitate calculations necessary for their biophysics course.

PyMol molecule movies: Students used the PyMol site to acquire molecular structures, introduce theoretical mutations, test the ability to dock smaller molecules, and to animate the interaction. Students posted these movies on YouTube and Facebook. http://www.Biologyshouldbefun.com site was created as this activity was developed.

Team projects: Students were assigned to teams, given specific topics to research, and then were responsible for presenting their findings.

Videos and web-‐based animation tools: These tools were incorporated into lectures, including IRACDA post-‐

Poster List

No. Presenter Category Title

1 Addison, Angela Immunology Testing Cytotoxicity of Compounds Found to be Effective Against TB/HIV Co-‐ infection

2 Ali, Shamsa Molecular and Cel

Biology Investigation of T-‐Cell Receptors Interacting Molecule (TRIM) on Natural Killer Cells in Mice

3 Anderson, Christopher Molecular and Cell Biology

XLF and XRCC4 Interact with Telomeric Proteins

4 Attia, John Molecular and Cell Biology

Hormonal Regulation of SMAD-‐4 in an Endometrial Cancer Cell Line, RL95-‐2 Cells

5 Baitemirova, Medina Structural and Computational

Biology/Bioinformatics

STQFinder : A bioinformatics tool to identify putative novel genes involved in the DNA damage response

6 Carnegie,Codi-‐anne Polymer Chemistry Syntheses and Characterization of Chitosan Acids

7 Chea,Chanmalis Microbiology Detection of the Plant Pathogen Xylella fastidiosa from an Experimental Vineyard to Find Grapevine Resistance to Pierce’s Disease

8 Dao, Cecilia Genetics

Determining the Lethal Concentration of Toluene on Drosophila melanogaster and the Resulting Morphological Effects of Toluene Exposure on Fly Offspring

8 Duong,Gina Molecular and Cell Biology

Determining the Lethal Concentration of Toluene on Drosophila melanogaster and the resulting morphological effects of toluene on fly offspring

8 Fisher,Katie Molecular and Cell Biology

Determining the Lethal Concentration of Toluene on Drosophila melanogaster and the resulting morphological effects of toluene on fly offspring

9 Grogan,Depresia Agriculture Survey of Functional Annotation for Selected Pathways for Agriculturally Important Species

8 Lam,Quy Molecular and Cell Biology


10 Manalo,Jeanne Molecular and Cell Biology

Using Yeast Two-‐hybrid to Investigate the Molecular Mechanism of Ku 70's 2nd Region

No. Presenter Category Title 11 Mansesh,Maryam Nanoparticles Photothermal Effects

12 Martinez, Anoinette Molecular and Cell

Biology uspE Gene Involved in E. Coli UV Stress Response

13 McClennon, Robert Polymer Chemistry Biodegradable Polymers as Potential Treatment for Food-‐borne Pathogens?

14 Neghina,Mihaela Microbiology FtsP Plays an Important Role in Temperature Response

15 Ponton,Robert Immunology Determining Innate Immune Response to Streptococcus pneumonia infection in the Cornea of Mice.

16 Reed,Theo Microbiology

Anti-‐ Salmonella Typhimurium Comparison of Broad-‐Rage Molecular Weight Chitosan Commercial Preparations and Specific Molecular Weight Chitosan Laboratory Preparations

8 Reinhart,Heidi Molecular and Cell Biology


17 Taylor,Derrick Molcular and Cell Biology

Biology Research

8 Ton,Maria Genetics Determining Lethal Concentration of Toulene on Drosophila Melanogaster

18 Valdez,Reyna Microbiology Detection of the Plant Pathogen Xylella fastidiosa from an Experimental Vineyard to Find Grapevine Resistance to Pierce’s Disease

19 Vo,Thiennga Biochemistry Site Directed Mutagenesis of Predicted E.coli Inner Membrane Protein YecN

20 Girgis,Irene Biochemistry Inhibition of Streptococcus mutans and Streptococcus salivarius in Oral Biofilms With Saffron and Turmeric Extracts

21 Mulkey,Leah Biology Diatom Anomaly at the Greens Bayou Wetlands Mitigation Bank

22 Morriss,Ginny(F) Biology Redirected splicing of pyruvate kinase M in the mouse heart

23 Salisbury,Elizabeth(F) Cancer Biology Peripheral nerves are a source of progenitor cells for bone formation in heterotopic ossification

24 Toneff, Michael(F) Molecular and Cellular Biology

Fluorescent sensors for the detection and isolation of epithelial to mesenchymal transition and cancer stem cells in breast cancer

25 Vela, Luz(F) Translational Biology Three-‐dimensional Enteroids as Novel Systems for the Study of Enteric Infections

26 Wright, Sara(F) Biochemistry & Molecular Biology

Determining the role fo GPCR signaling proteins on the activity of the metabotropic glutamate receptor, mGluR6

(F) Denotes IRACDA Fellow

Poster #23

Peripheral nerves are a source of progenitor cells for bone formation in heterotopic ossification

Elizabeth A. Salisbury1, ZaWaunyka W. Lazard1, Eric D. Beal II1, Elizabeth A. Olmsted-‐Davis1,3,4 and Alan R. Davis1,3,4 1Center for Cell and Gene Therapy, 2Department of Neurology, 3Department of Orthopedic Surgery, 4Department of Pediatric Hematology and Oncology, Baylor College of Medicine, Houston, TX, USA

We previously developed a mouse model of heterotopic ossification (HO), whereby delivery of bone morphogenetic protein 2 (BMP2) to the skeletal muscle initiates a crucial neuro-‐inflammatory response that leads to bone formation within the muscle. One outcome of neuro-‐inflammation is the degranulation of mast cells, which release proteases that remodel the matrix of the peripheral nerve. This ultimately facilitates the release of progenitors from the nerve itself. Two days after delivery of BMP2, we observed the replication of a population of perineurial fibroblasts expressing the β3-‐adrenergic receptor (ADRB3) and the neural migratory marker HNK1. Four days after BMP2 exposure, these ADRB3+ cells were found within the soft tissues surrounding the site of BMP2 delivery, but were absent from the nerves, suggesting the migration of this cell population. These cells also expressed the brown adipocyte marker uncoupling protein 1 (UCP1). Suppression of mast cell degranulation by cromolyn administration inhibited the generation of these brown adipocyte-‐like cells, ablating UCP1 gene and protein expression at the site. Interestingly, these cells create a hypoxic local environment that may be essential for chondrogenesis and express vascular endothelial growth factors to promote vessel formation. Additionally, we observed a significant expansion of claudin 5+ PDGFRα+ osterix+ endoneurial endothelial-‐like cells from nerves at the site of HO. We propose that these cells may be directly undergoing osteogenesis. The data collectively suggest that two key cells within the peripheral nerve, perineurial fibroblasts and endoneurial endothelial-‐like cells, may coordinately regulate each other resulting in chondrogenesis, new vessel formation, and osteogenesis.

REACH IRACDA Fellow Poster Abstracts Poster #22

Redirected splicing of pyruvate kinase M in the mouse heart

Ginny Morriss 1Center for Cell and Gene Therapy, 2Department of Neurology, 3Department of Orthopedic Surgery, 4Department of Pediatric Hematology and Oncology, Baylor College of Medicine, Houston, TX, USA

CTG-‐repeat expansion in the 3’-‐UTR of the DMPK gene leads to development of myotonic dystrophy type 1 (DM1), a multi-‐systemic disease affecting the heart and skeletal muscles. Cardiac defects in DM1, including conduction defects, arrhythmia, and dilated cardiomyopathy, occur in 80% of DM1 patients. CUG-‐repeat expansion in RNA alters developmentally regulated alternative splicing programs. A switch in pyruvate kinase M from the M1 isoform to the embryonic M2 isoform has been observed in DM1 skeletal muscle and correlates with suppression of glucose oxidative metabolism. PKM2 levels are also substantially up-‐regulated when expanded CUG repeats are expressed in the heart; however, the role of PKM2 in DM1 cardiac function has not been fully assessed. We injected mice systemically with an antisense oligonucleotide conjugated to a phosophorodiamidate morpholino internalization peptide (PPMO) to redirect splicing of PKM towards the M2 isoform in wild-‐type mice. We observed redirection of PKM splicing in the heart from 22% PKM2 expression in un-‐injected mice to 78.5% one week following systemic injection with PPMO-‐PKM2. The level of PKM2 decreased slightly to 69% 3 weeks post injection. Further analysis is required to determine if redirected splicing of PKM2 has phenotypic effects resembling the DM1 cardiac phenotype and whether these phenotypes are progressively worsened over time. Establishing how glucose metabolism is affected in the heart in response to increased PKM2 levels is critical since effective glucose metabolism is required to meet the high-‐energy demands of the heart and to support proper contractile function.

Poster #25

Three-‐dimensional Enteroids as Novel Systems for the Study of Enteric Infections

Luz E. Vela, Xiu-‐Lei Zeng, Mary K. Estes and Anthony Maresso

Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, Texas, USA

Infections of the intestinal tract are a leading cause of mortality worldwide. Progress in understanding such infections is hampered by poor model systems. Here, we describe the first use of 3-‐dimensional intestinal enteroids to study the pathogenesis of infections by diarrheagenic E. coli. Enteroids represent the precursors to the growth of tissues in situ, and, as such, contain mucin, a lumen, crypts, villi, and up to five different cell types. Hypothesizing that such structures will allow the study of E. coli, we demonstrate the successful colonization of enteroids of mouse and human origin with two E. coli pathotypes. We also demonstrate the functional characterization of these enteroids using immunofluorescence microscopy and Western blotting, and show we can control the dose, timing, and delivery of bacteria into such structures. Future studies will include the use of enteroids in the study of the native intestestinal microbiome. Be expanding the knowledge of how diarreahgenic E. coli cause disease in the intestine it will lead to better treatments against this global killer.

Poster #24

Fluorescent sensors for the detection and isolation of epithelial to mesenchymal transition and cancer stem cells in breast cancer

Michael J. Toneff,1; Herschkowitz, JI1; Knezevic, J1; Xin, L1; Mani, SA2; Rosen JM1 1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, 2Department of Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030

The epithelial to mesenchymal transition (EMT) endows epithelial-‐derived cancers, including breast cancer, with stem cell-‐like properties. Cancer stem cells (CSCs) are a subpopulation of tumor cells with the ability to evade standard therapeutics and initiate the growth of secondary tumors. In addition, EMT causes carcinoma cells to become invasive and is proposed to be necessary for metastasis. Therefore, a more thorough understanding of the mechanisms leading to an EMT/CSC phenotype could lead to the identification of novel therapeutic targets to reverse this aberrant cellular state and better treat cancer. The cellular mechanisms regulating EMT involve a complex network of cellular signaling pathways, transcription factors and microRNAs (miRNAs). Expression of the miR-‐200 family of miRNAs is strongly associated with an epithelial phenotype, and loss of its expression induces EMT. Overexpression of the miR-‐200 family was sufficient to reverse EMT in mammary epithelial cells that have undergone an EMT. Moreover, we have generated a p53 null mouse derived breast tumor model that displays an EMT phenotype and is similar to the claudin-‐low human breast cancer subtype. Overexpression of miR-‐200 in these tumors can reverse the EMT phenotype. We have developed and validated EMT sensors, including miR-‐200 sensors to allow the identification of cells displaying an EMT in in vivo mouse models and to identify drugs in high throughput screens that can reverse/inhibit EMT. The use of these sensors should facilitate the isolation of putative normal and cancer stem cell populations that exhibit EMT in mice. In addition, it should allow us to identify compounds that can modify critical EMT pathways to sensitize EMT/CSCs to standard breast cancer therapies.

IRACDA Fellow Abstracts Continued

Poster #26

Determining the role of GPCR signaling proteins on the activity of the metabotropic glutamate receptor, mGluR6

Sara J. Wright, Theodore G. Wensel

Department of Biochemistry, Baylor College of Medicine, Houston, TX 77030

Metabotropic glutamate receptors (mGluRs) are G-‐protein coupled receptors (GPCRs) that are responsible for sensing the neurotransmitter glutamate in the brain, retina, and other CNS tissues. In the retina, G protein signaling is crucial for detection and processing of light. Photons are sensed by the GPCR rhodopsin in rod photoreceptors, which leads to a halt in the release of glutamate at the photoreceptor/ON-‐bipolar cell synapse. ON-‐bipolar cells sense glutamate through the metabotropic glutamate receptor mGluR6. In the dark, photoreceptor cells release glutamate, which binds to mGluR6 and activates G protein signaling through G alpha o. This pathway is negatively regulated by RGS7 and RGS11, which are members of the R7 family of regulator of G protein signaling (RGS) proteins. It has been recently determined that the membrane localization of RGS7 is dependent on the orphan receptors GPR158 and GPR179. This project involves determining the effects of RGS7, GPR158, and other potential pathway players on the activity of mGluR6. Assays of mGluR6 activity will be done in cell culture using the FLIPR membrane potential assay. This assay detects changes in membrane potential in response to ion channel activation. Previous results have shown that this assay can be used to determine mGluR6 activity. In addition, localization of the pathway players will be studied in these cells using Immuno-‐fluorescence, as well as in retina and brain slices.

IRACDA Fellow Abstracts Continued

Acknowledgements Keynote Speaker

Chester Brown, M.D., Ph.D. Professor, Baylor College of Medicine

Houston, Texas

Graduate Student Speakers Berenice Carrillo, Ph.D.

AJ Hinton

Career Development Panel Alejandro Contreras, M.D., Ph.D.

Diane Scaduto, Ph.D Danielle Martinez, Ph.D. Adriana Visbal, Ph.D.

IRACDA Directors and Staff Gayle Slaughter, Ph.D. Laurie Connor Shante Romant Kerri Mejia

IRACDA Fellow Symposium Organizers

Michael Cato, Ph.D. Nina Poole, Ph.D.

Kathleen Quast, Ph.D. Lucy Vela, Ph.D. Ginny Morris, Ph.D.

Participating Partner Institutions Prairie View A&M University University of Saint Thomas

The University of Houston-‐Downtown

Sponsors VWR, Representative Trent Cullen

Prairie View A&M University Mentors:

Tamiko Porter, Ph.D. Gloria Regisford, Ph.D. Prekumar Saganti, Ph.D. Deirdre Vaden, Ph.D.

University of Houston-‐Downtown Mentors:

Jerry Johnson, Ph.D. J. Akif Uzman, Ph.D. Lisa Morano, Ph.D.

University of St. Thomas Mentors:

Ruth Bagnall, Ph.D. John Palasota, Ph.D. Rosie Rosell, Ph.D.

Alexandra Simmons, Ph.D. Maia Larios-‐Sanz, Ph.D.

PARTICIPATING INSTITUTIONS

5th Annual REACH IRACDA Symposium€¦ · Professor, Molecular and Cellular Biology Baylor College...

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