Plasmodium falciparum in theHuman Bone Marrow:The Malaria Headquarters?

Scientific Workshop

Agenda & Biographies

June 23-24, 2014 | Harvard Club of Boston

Scientific Workshop Agenda

8:00AM Breakfast (Estabrooks Room)

Welcome & Introductions (Bartlett Room) Workshop Organizers:Pietro Alano, Istituto Superiore di SanitàCatherine Lavazec, Institut CochinMatthias Marti, Harvard School of Public HealthAndy Waters, University of Glasgow

Opening RemarksVictoria McGovern, Burroughs Wellcome Fund

Session I: Parasite BiologyParasite Biology in the Context of Eradication (20min)Dyann Wirth, Harvard School of Public Health

Mechanisms of Parasite Adherence and Tissue Sequestration (10min)Joseph Smith, Seattle Biomedical Research Institute

Biology of Plasmodium Gametocytes (10min)Pietro Alano, Istituto Superiore di Sanità

Gametocyte Sequestration in Human Bone Marrow (10min)Matthias Marti, Harvard School of Public Health

Mechanical Properties of Gametocyte-infected Red Blood Cells (10min)Catherine Lavazec, Institut Cochin

Open Discussion

Break

Session II: Bone Marrow Biology (Bartlett Room)Human Bone Marrow as an Ecosystem (20min)Paolo Bianco, Sapienza Universita’ di Roma

Regulation of T cell Responses in Bone Marrow (10min)Ulrich von Andrian, Harvard Medical School

Hematopoiesis (10min)Mohandas Narla, New York Blood Center

Bone Marrow and Infection (10min)Robert Hasserjian, Harvard Medical School & MGH

8:45AM

9:00AM

10:00AM

10:30AM

11:00AM

Monday, June 23, 2014

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Out of the Bone Marrow, Mesenchymal Stem Cells Keep Supporting Hematopoietic Stem Cells (10min)

Mauro Valtieri, Istituto Superiore di Sanità

Open Discussion

Lunch (Estabrooks Room)

Session III: Parasite Biology (continued) (Bartlett Room)

Receptor Ligand Interactions in P. falciparum Gametocytes (10min)

Francesco Silvestrini, Istituto Superiore di Sanità

Parasite Infection in the Human Bone Marrow and Malaria Pathology (10min)

Alfredo Mayor, Universidad de Barcelona

Role of the Spleen in Parasite Clearance and Sequestration (10min)

Pierre Buffet, Pitié-Salpêtrière Hospital

Mouse Malaria Models to Study Gametocyte Biology (10min)

Andy Waters, University of Glasgow

Sequestration of Latent TB in Human Bone Marrow (10min)

Antonio Campos-Neto, Forsyth Institute

Open Discussion

Wrap-up Session & RemarksPaolo Bianco, Sapienza Universita’ di Roma

Dyann Wirth, Harvard School of Public Health

Adjourn

Group DinnerTowne Stove & Spirits

900 Boylston Street

Boston, MA

12:00PM

12:30PM

2:30PM

3:20PM

4:30PM

7:00PM

Tuesday, June 24, 2014Breakfast (Estabrooks Room)

Session IV: Relevant Models & Methodologies (Bartlett

Room)

Imaging Approaches in Malaria (10min)

Leann Tilley, University of Melbourne

In vitro Erythroid Development and Malaria Infection (10min)

Manoj Duraisingh, Harvard School of Public Health

8:00AM

9:00AM

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Humanized Mouse Model for P. falciparum Infection (10min)Alicia Moreno-Sabater, CIMI-Paris

In vivo Models of the Human Bone Marrow Microenvironment (10min)Mara Riminucci, Sapienza Universita’ di Roma

Tissue Engineering Approaches (10min)Biju Parekkadan, Harvard Medical School

Assays to Study Bone Marrow Homing and Transmigration (10min)Christopher Carman, Beth Israel Deaconess Medical Center

Open Discussion

Break

Session V: Open Questions, Ways Forward & Tools to Bridge a Century-old Knowledge Gap (Bartlett Room)

Open DiscussionSelect topics: basic biology, model systems, translational implications, and future outlook

Lunch (Estabrooks Room)

Session VI: Biology of Malaria Transmission & Funding Opportunities within an Eradication Context (Bartlett Room)Transmission Biology Across Plasmodium Species (10min)Colin Sutherland, London School of Hygiene & Tropical Medicine

Experimental Infections to Define Malaria Transmission Dynamics (10min)Robert Sauerwein, Radboud University Nijmegen

Perspective of PATH Malaria Vaccine Initiative (MVI) and Bill & Melinda Gates FoundationAshley Birkett, PATH Malaria Vaccine InitiativeChris Karp, Bill & Melinda Gates FoundationOmar Vandal, Bill & Melinda Gates Foundation

Open Discussion

Closing RemarksDyann Wirth, Harvard School of Public Health

10:00AM

10:30AM

11:00AM

12:00PM

2:00PM

2:40PM

3:30PM

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Participant BiographiesPietro AlanoSenior Researcher Istituto Superiore di Sanità

at the course Biology of Parasitism (MBL, Woods Hole, MA), his interest in the host-parasite interplay led him in 1987 to study the molecular mechanisms of sexual differentiation of the human malaria parasite Plasmodium falciparum with Richard Carter at the University of Edinburgh. In 1991, Pietro joined the laboratory of Clara Frontali at the Istituto Superiore di Sanità in Rome, Italy, where he eventually established his research on the cellular and molecular biology of human malaria parasite transmission. In the past twenty years Pietro’s team has developed molecular markers, transgenic reporter lines and transcriptomics and proteomics data to elucidate mechanisms of gene regulation of developmental decisions and of parasite interactions with host cells and tissues in the course of P. falciparum gametocyte formation. This expertise is presently used to develop diagnostic tools for epidemiology of malaria transmission and novel cell-based assays to screen for transmission blocking drugs, as well as to address fundamental unanswered questions in the biology of P. falciparum sexual differentiation and the interplay of this parasite with the human host. Pietro’s team is presently funded by the Italian Ministry of Health, the European Commission, and the Bill & Melinda Gates Foundation.

Pietro Alano obtained a degree in Biology (1983) and a PhD in Molecular and Cellular Biology (1986) at the University of Milan, Italy, studying the genetic regulation of bacteriophage life style in E. coli. After approaching the field of molecular parasitology in 1986,

Paolo BiancoProfessor, Pathology Director, Anatomic PathologyChief, Stem Cell LaboratoryDepartment of Molecular MedicineSapienza Universita’ di Roma

Professor Paolo Bianco works on skeletal diseases and non-hematopoietic stem cells found in the bone marrow stroma. His work focuses on the role of these cells in skeletal and hematopoietic physiology, with special reference to the hematopoietic niche. A second focus of his work is on the crucial role of stem cell in genetic diseases of the skeleton, in particular fibrous dysplasia (FD, OMIM#17480). His work has identified and characterized postnatal progenitors in the human bone marrow as subendothelial cells, and the definition of tissue-specific progenitors in microvascular niches in different tissues. A specific facet of this issue is represented by the role of skeletal stem cells in providing a niche for hematopoietic and cancer cells homing to bone. Professor

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Bianco has published over 170 peer reviewed papers and 35 chapters, and has served on multiple editorial and scientific boards. Among other commitments, he currently serves as Associate Editor for Stem Cell Research. He was the recipient of the ISSCR Public Service Award in 2014.

Ashley BirkettDirector PATH Malaria Vaccine Initiative

Ashley Birkett’s appointment as Director of the PATH Malaria Vaccine Initiative (MVI), one of eight global programs at PATH, took effect in October 2013. Ashley was most recently MVI’s Deputy Director, serving

simultaneously as Director of Research and Development (R&D)—the latter a position he has held since joining PATH in 2008. In his position as Director of R&D at MVI, Ashley has led MVI’s efforts to support the development of transmission-blocking vaccines. He also has guided MVI’s portfolio of evaluation technology projects, which are developing and refining ways to assess vaccine efficacy prior to large-scale field trials, and provided technical support across the range of MVI’s vaccine development programs, including the RTS,S program. Ashley has more than 15 years of vaccine development experience, primarily with biotechnology companies, where he successfully advanced novel influenza and malaria vaccine candidates from research through first-in-human clinical studies. Prior to joining MVI, he was Senior Director of Preclinical Research at Acambis (now Sanofi Pasteur Biologics Co.), where he had responsibility for the company's global preclinical vaccine research portfolio, with a special focus on influenza and adjuvant technology identification. Prior to Acambis, he served in a similar role at Apovia Inc. Between 1997 and 2004, he led the Malaria Vaccine Program housed first at Immune Complex Corporation and then at Apovia. This program was the first corporate partnership for MVI after its founding as a program of PATH in 1999. Birkett earned a PhD in Biochemistry and Molecular Biophysics from Virginia Commonwealth University; he has a BSc (Honors) in Applied Biological Sciences from the University of the West of England in the United Kingdom.

Sandrine BourdoulousResearch Director & Principal InvestigatorInstitut Cochin

Sandrine Bourdoulous is Research Director and Principal Investigator at the Institut Cochin, Paris, France. She studied Biochemistry and Immunology at the Université Paris Diderot and obtained her PhD in

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Immunology in 1994, working on the regulation of leukocyte infiltration in the central nervous system. After serving as a postdoctoral fellow for three years in the laboratory of Dr. Erkki Ruoslahti at the Burnham Institute (La Jolla, California, USA), where she investigated integrin-mediated cell adhesion mechanisms in normal and cancer cells, she obtained a position at the French National Center for Scientific Research (CNRS) in 1997. Since 2005, she has served as a Team Leader at the Cochin Institute in Paris. Her team is conducting basic and translational research on adhesion and signalling receptors involved in leukocyte and pathogen trafficking across the endothelial barriers. Her team has had a long standing research interest in the molecular interaction of bacterial pathogen (Neisseria meningitidis) and leukocytes with the vascular wall. Bourdoulous is a a recognised expert on adhesion molecules and receptor signaling that govern vascular plasticity and vascular dysfunctions induced in inflammatory and infectious diseases.

Pierre BuffetAssociate Professor of ParasitologyPitié-Salpêtrière HospitalHead of Research Team, Parasites Erythrocytes PathogenesisINSERM - University Pierre & Marie Curie

Professor Buffet is a trained physician with a specialization in Dermatology and a special interest in tropical diseases (Paris University 1983 – 1995). He conducted research as an invited physician/scientist in Medellin, Colombia (1991 – 1992, Parasitology Department) and Rio, Brazil (1995 – 1996, Instituto de Biologia/US Army Medical Research Unit), working on the therapy of leishmaniasis. He obtained his PhD in Microbial Biochemistry at Institut Pasteur on gestational malaria and virulence factors of Plasmodium falciparum (Artur Scherf lab,1996 – 2000) and completed a fellowship in infectious diseases at Necker Hospital in Paris (1998 – 2001). He then served as Head of Medical Center and Clinical Research Center at Institut Pasteur, Paris (2001 – 2007) developing projects on splenic physiology and interactions between P. falciparum-infected red blood cells and the microcirculation. He has authored 83 articles, 4 patents, and 1500 citations (ISI Web of Knoweldge). Professor Buffet has served as Principal Investigator on clinical trials and surveillance programs in clinical parasitology. He is a consultant for Sanofi, DNDi, and Sigma Tau on antiparasitic drugs. He is also a member of the Board of the French National Reference Center for Malaria. He acts as a reviewer for 35 international journals, is an expert for the French Drug Agency (ANSM, Antimalarial drugs), and as adviser for WHO (leishmaniasis). He is a member of the National INSERM Commission “Immunology & Infectious Diseases,” and a Member of the French Laboratory of Excellence on Red Cells. He was awarded the “Research Excellence Award 2012,” by Pierre & Marie Curie University.

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Antonio Campos-NetoSenior Member, Department of Immunology & Infectious Diseases, The Forsyth InstituteDirector, Center for Global Infectious Disease Research & Lecturer in Oral Medicine, Infection & Immunity Harvard School of Dental Medicine

Dr. Campos-Neto graduated in Medicine in Brazil and was subsequently trained in Immunology as a postdoctoral fellow at Harvard Medical School, Boston, MA. Most of his research interest has been centered on immunology of infectious diseases with special emphasis on tuberculosis and leishmaniasis. Recently, in collaboration with Dr. Bikul Das, he discovered that Mycobacterium tuberculosis maintains long-term intracellular viability in a human bone marrow (BM)-derived CD271+/CD45- mesenchymal stem cell (BM-MSC) population, both in vitro as well as in BM-MSCs isolated from individuals who had successfully completed months of anti-tuberculosis drug treatment. An equivalent population of M. tuberculosis-infected BM-MSCs was also present and detected in both lungs and BM of a stringent the mouse model of latent tuberculosis. These results strongly suggest that BM-MSCs provide a long-term protective intracellular niche in which M. tuberculosis can reside and be protected from the host immune attack and from drugs. Dr. Campos-Neto’s laboratory is currently expanding these observations to visceral leishmaniasis a disease also caused by an intra-cellular pathogen.

Christopher V. CarmanAssistant Professor of MedicineHarvard Medical SchoolBeth Israel Deaconess Medical Center

Christopher Carman earned a PhD in Molecular Pharmacology and Structural Biology from Thomas Jefferson University, Philadelphia, PA in 1999. He then

performed a post-doctoral study at Harvard Medical School with Timothy A. Springer. In 2006 Dr. Carman joined the Division of Molecular and Vascular Medicine at Beth Israel Deaconess Medical Center and became a member of the Center for Vascular Biology Research. The Carman laboratory investigates the cell biological basis of inflammation and wound healing with special emphasis on leukocyte-endothelial interactions. The vascular endothelium is the monolayer of cells that lines the cardiovascular system and serves as the critical barrier between the tissues and the blood. Thus, the endothelium is strategically positioned to serve as a unique sentinel for communicating interstitial information to the circulating immune cells (i.e., leukocytes). In this way, the endothelium plays critical roles in directing the trafficking patterns, as well as activation states of leukocytes. The endothelium can also become damaged by inappropriate immune/inflammatory responses, creating a dysfunctional barrier that gives rise

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to many of the pathogenic features of inflammatory diseases such as sepsis, anaphylaxis, multiple sclerosis and arthritis. Dr. Carman work makes extensive use of advanced fluorescence imaging, electron microscopy and biomechanical approaches to understand the fundamental basis and consequences of leukocyte-endothelial interactions and how they may become perturbed during inflammatory and immune-related diseases.

Flaminia CatterucciaAssociate ProfessorImmunology & Infectious DiseasesHarvard School of Public Health

of scientists that focus on the analysis of the molecular and genetic basis underlying mating and reproduction in An. gambiae s.s.. The main research focus of the group is the study of the genetic basis of fertilization and mating behavior in Anopheles gambiae mosquitoes, the major malaria vectors, with the view to answer basic biological questions and develop new molecular and genetic tools for vector control programs. Her research aims at answering basic biological questions as well as developing new tools for vector control programs. Dr. &DWWHUXFFLD�DFKLHYHGɾWKH�ILUVW�JHQHWLF�PDQLSXODWLRQ�RI�$QRSKHOHVɾPRVTXLWRHVɾDQG�has contributed to the development of a number of molecular tools to perform functional studies in Anopheles. Her work includes field studies to confirm and expand the laboratory findings of her research group.

Dr. Flaminia Catteruccia is Associate Professor in the Department of Immunology and Infectious Diseases in the Harvard School of Public Health. She leads a group

Matthew DixonNHMRC FellowDepartment of Biochemistry & Molecular Biology University of Melbourne

University of Melbourne. Dr. Dixon’s research focuses on understanding the remodeling and cell biology processes driving the unique architectural changes undertaken by the human malaria parasite Plasmodium falciparum. In particular his research focuses on the unusual protein trafficking pathways and structures that the malaria parasite uses to remodel the RBC membrane and display virulence proteins at the erythrocyte surface. These changes are central to the parasite's ability to survive within the red blood cells and circulation of the human host. In particular he is interested in the processes mediating cerebral and placental malaria and the mechanisms of sexual differentiation and transmission.

Matthew Dixon is an NHMRC Fellow in the Department of Biochemistry and Molecular Biology in the Bio21 Molecular Science and Biotechnology Institute, at the

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Manoj DuraisinghProfessor Immunology & Infectious DiseasesHarvard School of Public Health

Manoj Duraisingh joined the Harvard School of Public Health in 2002, and is a Professor in the Department of Immunology and Infectious Diseases. He is also an

Associate Member at the Broad Institute, and a Burroughs Wellcome Fund New Investigator in the Pathogenesis of Infectious Diseases. He obtained his BA in Biochemistry from the University of Oxford, and an MSc and PhD in Molecular Parasitology from the London School of Hygiene and Tropical Medicine, conducting research on the molecular mechanisms of drug-resistance in the malaria parasite. Before joining the Harvard School of Public Health, Professor Duraisingh pursued postdoctoral research in molecular parasitology at the Walter and Eliza Hall Institute, applying molecular genetic approaches to study host cell invasion and the epigenetic regulation of malaria parasites. Professor Duraisingh’s research program focuses on the biology of host-parasite interactions in malaria. He is a world leader in the latest technologies associated with P. falciparum molecular genetics and has trained many researchers in these techniques. His laboratory uses transfection-based molecular and cell biological approaches to study the molecular mechanisms underlying the recognition and invasion of the human erythrocyte by the malaria parasite, and epigenetic regulation of multigene families that govern virulence processes in Plasmodium-infected erythrocytes. More recently, reverse genetic methods have been developed to functionally analyze host red blood cell determinants of malaria infection. Efforts are being made towards establishing in vitro culture and genetic systems for other human Plasmodium parasites, including P. vivax and P. knowlesi. Professor Duraisingh is also engaged in field projects with collaborators and training programs in malaria-endemic areas, in particular Senegal, focused on studying parasite and host genetic determinants of malaria infection in natural populations.

Manjit HanspalProgram DirectorDivision of Blood Diseases and Resources National Heart, Lung, and Blood InstituteNational Institutes of Health

Dr. Manjit Hanspal received her PhD in Biochemistry from Sydney University in Australia, and completed a postdoctoral fellowship at Harvard University. Dr.

Hanspal then joined St. Elizabeth’s Medical Center, Tufts University School of Medicine in Boston, MA, where she spent the next two decades studying red cell

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membrane skeleton biogenesis, erythropoiesis, erythroblast-macrophage interactions in the bone marrow, and the role of cysteine proteases in the biology of malaria parasite, Plasmodium falciparum. In December 2007, Dr. Hanspal joined NIH where she serves as Program Director in the Division of Blood Diseases and Resources, National Heart, Lung, and Blood Institute. As a Program Director, she develops new programs targeted on various aspects of hematology research; and manages a portfolio of research grants focusing on investigations of molecular and cellular mechanisms regulating terminal erythroid differentiation; acquired and congenital red cell disorders; erythrocyte membrane structure and function; erythrocytic life-cycle of malaria parasite; vascular dysfunction in malaria pathogenesis; sickle cell disease; and thalassemia.

Robert HasserjianAssociate ProfessorPathologyMassachusetts General HospitalHarvard Medical SchoolDr. Robert Hasserjian is an Associate Professor of Pathology at Massachusetts General Hospital and Harvard Medical School. He is Director of the

Hematopathology Fellowship and Associate Director of the Pathology Residency Program at Massachusetts General Hospital. Dr. Hasserjian received his MD degree from Harvard Medical School in 1990 and trained in Anatomic Pathology and Hematopathology at Brigham and Women's Hospital. Dr. Hasserjian’s clinical expertise is in the area of diagnostic hematopathology, with particular interest in diseases of the bone marrow and distinguishing reactive bone marrow processes from neoplasms. He participated in the 2008 WHO Classification of Myeloid Neoplasms.

Christopher KarpDeputy DirectorGlobal Health Discovery & Translational SciencesBill & Melinda Gates Foundation

Chris Karp, Deputy Director of the foundation’s Global Health Discovery & Translational Sciences program, leads the Vaccines & Host-Pathogen Biology team that

targets fundamental scientific and technological advances in global health that could lead to new ways to prevent and treat disease. An immunologist, infectious diseases specialist, and internist, Chris joined the foundation in 2012. Prior to the foundation, he was on the faculty of the Departments of Medicine and Molecular Microbiology and Immunology at Johns Hopkins University School of Medicine.

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He founded the Division of Molecular Immunology at Cincinnati Children's Hospital Research Foundation, where he was Esiason/Bell Professor of Pediatrics. His academic scientific career focused on defining the mechanisms underlying the regulation and dysregulation of inflammatory responses in infectious, allergic and genetic diseases, with a focus on diseases of children and diseases of increased prevalence in the tropics. Chris received an undergraduate degree (summa cum laude, with high honors in Philosophy) from Brandeis University and an MD from the University of North Carolina School of Medicine, where he was a Morehead Fellow. He trained in Medicine at Brown University and Georgetown University, and then was a post-doctoral fellow in the Laboratory of Parasitic Diseases at NIAID, and an infectious diseases fellow at Johns Hopkins.

Catherine LavazecHead of Biology of Plasmodium Transmission TeamInstitut Cochin, An Affiliate with INSERM & the University Paris Descartes

Catherine Lavazec’s research interest is focused on understanding the mechanisms of malaria parasites

transmission. Her PhD work at Pasteur Institute, between 2000 and 2004, resulted in the identification of a target for a Plasmodium transmission-blocking vaccine based on a mosquito antigen. During her post-doctoral studies at Cornell Universityin New York and at Pasteur Institute in Paris, she contributed to the characterization of a mosquito protein family involved in immune resistance against Plasmodium infection, and of several Plasmodium protein families involved in parasite antigenic variation and in parasite transmission. Particularly, she has characterized a parasite protein family that impacts erythrocyte mechanical properties during asexual and sexual stages. Since 2010, she has developed her own independent research focused on the mechanical properties of erythrocytes infected with P. falciparum gametocytes. In collaboration with Pietro Alano, she has described changes in mechanical properties during gametocyte maturation that may be crucial for gametocytes sequestration and circulation in the human host. She has identified parasite proteins and signaling pathways that participate to this process, and her ongoing studies supported by the BMGF focus on the identification of drugs that affect gametocyte circulation.

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Rebecca LeePhD CandidateUniversity of Glasgow

Rebecca is a first year PhD student within the Wellcome Trust Centre for Molecular Parasitology at the University of Glasgow. Her research interests include the dynamics of mature gametocytes within infection

and the subsequent implications for malaria transmission. In particular, she is interested in combining intravital multiphoton microscopy with biophysical techniques to study the mature gametocytes of Plasmodium berghei. Having won a 3.5 year MRC studentship, Rebecca’s current work is being carried out under the supervision of Professor Waters and Professor Brewer. Rebecca graduated from the University of Edinburgh with a BSc (Hons) in Molecular Genetics. She went on to study for an M.Res in Molecular Parasitology at the University of Glasgow from which she graduated with distinction. During her Master’s research, Rebecca worked with Dr. Ranford-Cartwright investigating the invasion efficiency of P. falciparum merozoites. She also worked with Dr. De Koning on characterizing a novel Trypanosoma brucei drug transporter, research that resulted in Rebecca’s first publication.

Amanda LukensResearch ScientistThe Broad Institute

Dr. Lukens studies various aspects of malaria parasites with a focus on understanding the underlying genetic basis of biological phenotypes. Her work has utilized genetic and transcriptome analysis of clinical isolates to

understand the selective forces in the extant parasite population, including host immune responses and drug pressure. Her current research interests center on utilizing genomic tools to identify novel vaccine candidates and understanding the targets of small molecule inhibitors in the drug-development pipeline. She aims to determine the consequences of mutations that contribute to immune evasion and drug resistance, setting the foundation for efforts to design new vaccines and combination therapies to prevent the emergence of escape or resistance in nature.

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Francis W. (Bill) LuscinskasProfessor, PathologyHarvard Medical School

Francis W. (Bill) Luscinskas received his BS from Northeastern University in Boston, MA and his PhD in Biochemistry from Boston University. He performed postdoctoral training in the lab of Dr. Michael A.

Gimbrone at the Brigham and Women’s Hospital in Boston, MA. Dr. Luscinskas is currently Professor of Pathology at Harvard Medical School and his research lab is located in the Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women’s Hospital. The Luscinskas lab research is focused on understanding the endothelial cell dependent mechanisms that regulate inflammatory and immune responses, and how these processes become dysregulated in cardiovascular disease. Our focus has been on exploring the role of endothelial cell adhesion molecules and their communication with adherens junctional protein complexes to regulate leukocyte transmigration using in vitro and in vivo models. Recent publications have examined the molecular and cellular mechanisms that enable CD47 to modulate the function of leukocyte LFA-1 and VLA-4 integrins (Mol Biol Cell 2013; 24:3358-68). We have also found that endothelial CD47 transmits intracellular signals upon engagement and plays an important role in leukocyte transmigration (Arterioler Thromb Vasc Biol 2013;33:2566-76).

Matthias MartiAssociate ProfessorImmunology & Infectious DiseasesHarvard School of Public Health

Dr. Matthias Marti is an Associate Professor of Immunology and Infectious Diseases at the Harvard School of Public Health, with an appointment at the

School since 2007. He obtained his Masters degree in Medical Parasitology at the Swiss Public Tropical and Public Health Institute on the subject of development of a drug screen for the intestinal parasite, Giardia lamblia. After training in molecular parasitology at the University of Texas at El Paso he did a PhD on mechanisms of protein secretion in Giardia at the University of Zurich. During the following postdoctoral work at the Walter and Eliza Hall Institute in Melbourne, Australia, Dr. Marti identified a novel protein secretion mechanism in human malaria parasites. Dr. Marti’s research efforts are focused on basic and translational aspects of malaria transmission stages. Current efforts for malaria elimination and eventual eradication have generated renewed interest in the

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biology of malaria transmission and transmission blocking interventions. The Marti lab has developed the first high throughput screen targeting malaria transmission stages. More recent work focuses on development of tools for the detection and quantification of malaria transmission stages during human infection. The lab is studying the formation and development of these stages in human red blood cells using an in vitro model and during human infection. These studies have revealed a unique sequestration site in the human bone marrow. Dr. Marti is involved in several field collaborations in Malawi and Nigeria.

Alfredo MayorAssociate Research ProfessorBarcelona Center for International Health ResearchHospital Clinic-Universidad de Barcelona

Alfredo Mayor started his work on malaria in 1996 when he described during his PhD the molecular epidemiology of P. falciparum in southern Mozambique. During

his postdoctoral research at the International Center for Genetic Engineering and Biotechnology (ICGEB, New Delhi, India), he developed molecular methods to map the receptor-binding residues of P. falciparum molecules, opening up the path toward understanding the basis of these interactions and the natural acquisition of immunity. In 2004, he returned to Spain and started his research at the Barcelona Center for International Health Research (CRESIB), where he has focused on the physiopathology of severe malaria in pregnant women and children, with a special interest on the identification of clinically relevant cytoadhesion phenotypes in P. falciparum and P. vivax, the host and parasite molecules involved as well as the targets of protective immune mechanisms. In collaboration with Dr. Matthias Marti and Dr. Clara Menéndez, he has recently shown the high prevalence and abundance of early sexual stages in bone marrow, as well as a relationship between hematological disturbances and gametocyte development in this tissue. Dr. Mayor is collaborating with the Manhiça Health Research Center, in Mozambique.

Ralph MazitschekAssistant Professor, RadiologyMassachusetts General Hospital

Dr. Mazitschek is an Assistant Professor at Harvard Medical School and Co-Director of the Chemical Biology Platform at the Center for Systems Biology at

Massachusetts General Hospital (MGH). Dr. Mazitschek is also a member of the

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Infectious Diseases Initiative at The Broad Institute of Harvard and MIT, associate Faculty at the Center for Human Genetic Research at MGH and Visiting Scientist at the Department of Immunology and Infectious Diseases at Harvard School of Public Health. Dr. Mazitschek graduated from the University of Leipzig in 2002 with a PhD in Organic Chemistry. He continued his research at the Institute of Chemistry and Cell Biology (ICCB) at Harvard Medical School first as postdoc and later as Institute Fellow, from which he joined the Chemical Biology Program at the newly founded Broad Institute of Harvard and MIT. In 2008 he joined the faculty of the Center for Systems Biology at the Massachusetts General Hospital to continue his independent research.

James McCarthyProfessor, NHMRC Practitioner Fellow & Senior ScientistClinical Tropical Medicine Laboratory Queensland Institute of Medical Research

Fellow. He heads the Clinical Tropical Medicine Laboratory at QIMR where he leads a research program in tropical diseases and parasitology at the interface of basic research and clinical translation. His major research focus is on the development and application of an experimental induced blood stage malaria system. In the past 4 years, he has undertaken 9 clinical trials with this system, 7 with P. falciparum and 2 with P. vivax. Although the principal aims of these studies have been to accelerate antimalarial drug development, they have provided unique opportunities to improve understanding of the pathology and immune response in early malaria. Using this system he has accumulated evidence of the propensity of a range of licensed and experimental antimalarial drugs to influence commitment gametocytogenesis in vivo.

James McCarthy is an Australian NHMRC Practitioner

Victoria McGovernSenior Program OfficerBurroughs Wellcome Fund

Victoria McGovern, PhD is a Senior Program Officer at the Burroughs Wellcome Fund (BWF). She runs the Fund’s programs in Infectious Diseases and in

Population and Laboratory Based Sciences. For more than 20 years she has been involved in science policy efforts related to strengthening the scientific workforce, an interest she continues at BWF. Victoria earned bachelor’s degrees in Biology and

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in English Literature at Washington University and a PhD in Biochemistry at the

University of Alabama at Birmingham, followed by a postdoctoral fellowship in

Marine Biotechnology at the Cameron Applied Research Center in Charlotte, NC.

Her scientific work centered on chromosome structure and she maintains a

continuing interest in the functional analysis and structure of whole genomes,

including by managing the Fund’s investments in pathogen genomics and post-

genomics. She is an established science writer, a past chair of Sigma Xi’s Committee

on Public Understanding of Science, and one of the first correspondents for

Science’s Next Wave, Science’s online careers magazine. She currently serves on the

National Postdoctoral Association’s advisory board, the Committee on Postdoctoral

and Graduate Education of the American Society for Microbiology, and the Council

of the American Society for Tropical Medicine and Hygiene. She joined the Fund in

1997.

Pedro MejiaYerby Postdoctoral Research Fellow

Department of Genetics & Complex Diseases

Harvard School of Public Health

host nutritional status and the immunopathology of cerebral malaria. The

nutritional status of the patient has long been suspected to play a major role in

disease outcome in malaria, but the effects of specific nutrient deficiencies remain

controversial and poorly characterized. Using an experimental model of severe

malaria Pedro aims to define host nutritional and genetic factors modulating

disease outcome.

Working under the supervision of Professor James

Mitchell, Pedro Mejia studies the interaction between the

James MitchellAssociate Professor

Genetics and Complex Diseases

Harvard School of Public Health

Dr. James Mitchell’s research interests center on

nutrition, stress, and aging. Experiments in the Mitchell

laboratory are focused on nutritional and genetic determinants of adaptive stress resistance upon dietary restriction (reduced food

intake without malnutrition) in rodent models, and its potential beneficial

applications in humans. Recently, in collaboration with colleagues in Department

of Immunology and Infectious Diseases, Dr. Mitchell has begun to explore the

interaction between host diet and malaria infection in a mouse model of

experimental cerebral malaria.

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Alicia Moreno-SabaterCIMI-Paris, Faculté de Médecine Pierre et Marie Curie

Alicia Moreno Sabater trained as a student in Pharmacy in Valencia, Spain (1990-96), and obtained her PhD in Dr. Druilhe’s Unit at Pasteur Institute, Paris, France (1997-2000). She completed her Post-doctoral research in Dr. Benito’s Laboratory at the National Institute of Tropical Medicine (ISCIII) Madrid, Spain (2001-05). She has a UPMC permanent position as IR in Pr. Mazier’s Team (CIMI-Paris). She has a track record in the field of humanized mouse models infected with the human Plasmodium falciparum, vivax and ovale parasites. She was among the first scientists to obtain the asexual and sexual erythrocytic cycle of P. falciparum in a humanized mouse model and to show its usefulness to study defense mechanisms and chemotherapy. In the last years, she has been involved in the study of blood brain barrier damage induced by adhesion of P. falciparum parasitized cells. She is also involved in the development of a new transgenic and humanized mouse model aimed to mimic adhesion of P. falciparum parasitized cells to mouse brain endothelium, and its involvement in the cerebral malaria onset.

Mohandas NarlaVice President, ResearchDirector, Lindsley F. Kimball Research Institute New York Blood Center

Dr. Mohandas Narla received his doctoral degree from Washington University in St. Louis in Chemical

Engineering. After completing post-doctoral training in Hematology research with Dr. Marcel Bessis in Paris, he joined the faculty of the Department of Laboratory Medicine at University of California where he spent 13 years. In 1989, he moved to Lawrence Berkeley National Laboratory, University of California to head the Hematopoiesis group. In 2001, he moved to the New York Blood Center. Dr. Narla’s scientific interests over the last 40 years focused on red cell physiology and pathology. In particular, his efforts have contributed to improved understanding of the molecular and structural basis for red cell membrane disorders, developing detailed mechanistic insights into pathophysiology of thalassemias and sickle cell anemia, characterizing structural and functional changes induced in red cells by the malarial parasite, Plasmodium falciparum. More recently he has focused his research efforts on molecular understanding of erythropoiesis with particular emphasis on disordered erythropoiesis including and congenital erythroblasopenias. He has published 345 peer-reviewed publications and 100 reviews articles and book chapeters. Dr. Mohandas served as a member of the NIH Hematology study section for 13 years and was Associate Editor of Blood from 2003-2012.

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Biju ParekkadanAssistant Professor, Surgery (Bioengineering) Harvard Medical SchoolMassachusetts General Hospital

A significant challenge in drug development is to build realistic, pre-clinical models that accurately predict

human physiological responses. The bone marrow, in particular, is a vital organ that is limited in study because of its anatomical inaccessibility, tissue complexity, and lack of relevant model systems with good experimental throughput. At the Parekkadan group, they present an implantable humanized stem cell niche that can support hematopoietic progenitor cells in an accessible, ectopic site under the skin for in situ analysis. Using intravital imaging and fluorescence-computed tomography they show in real time that implant forms a vascularized, hematopoietic inductive microenvironment that can recruit endogenous and transplanted bone marrow cells with single cell resolution. This technology can enable the study of a human bone marrow microenvironment with user-defined inputs that are built into the implanted construct.

Mark ParringtonSenior Director & Head of Technology Projects GroupDiscovery Research NASanofi Pasteur

Dr. Parrington has 22 years of industry experience in the research and development of live attenuated, vector-

and subunit-based vaccines against viral and bacterial pathogens, and cancer. He joined Research at Sanofi Pasteur in 1991 and has held a number of roles in the company including, Head of Recombinant Vaccines, Director of the Microbiology Department and Canadian Head of Discovery Research. His research interests have been in the fields of DNA and RNA immunization, viral vector delivery systems, inactivated viruses, protein expression systems and subunit vaccines, targeting Influenza, Respiratory Syncytial virus, Parainfluenza viruses, Hantaviruses, HIV, Herpesviruses, Chlamydia, Streptococcus pneumoniae, and cancer targets including Melanoma and Colorectal. Sanofi Pasteur has almost 20 years experience in Malaria vaccine development, including two clinical trials. One was a Phase I/II safety, immunogenicity, and efficacy trial testing an attenuated poxvirus vector expressing 7 different P. falciparum antigens (NYVAC-Pf7). The other was a Phase I trial, testing a DNA vaccine expressing P. falciparum CSP. Dr. Parrington is currently leading an initiative to assess how the malaria vaccine landscape has changed since our last Malaria vaccine project. He obtained his PhD in the field

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of Molecular Virology from the University of Ottawa. Dr. Parrington is an author on 11 scientific publications and an inventor on over 20 patents/patent applications.

Zhangli PengPostdoctoral FellowNanomechanics LaboratoryDepartment of Materials Science & EngineeringMassachusetts Institute of Technology

research in the Nanomechanics Laboratory in the Department of Materials Science and Engineering at Massachusetts Institute of Technology. He will move to the Department of Aerospace and Mechanical Engineering in the University of Notre Dame as an Assistant Professor in Fall 2014. He obtained his PhD from the University of California San Diego. His main research area is multiscale modeling of cell/tissue biomechanics and related diseases, such as malaria and sickle cell disease. In addition, he also studied several kinds of bio-inspired structures, such as a flow energy harvester inspired by fish swimming, nacre shells and tensegrity structures.

Zhangli Peng is currently carrying out his postdoctoral

Regina RabinovichExxonMobil Malaria Scholar in ResidenceHarvard University

Dr. N. Regina Rabinovich is the 2012-2015 ExxonMobil Malaria Scholar in Residence at Harvard University. She is a global health leader with over 25 years’

experience in the research, public health, and philanthropic sectors, with focus on strategy, analytics, global health product development, and the introduction and scale-up of tools and strategies resulting in impact on endemic populations. Prior to joining Harvard University, she served as the Director of the Infectious Diseases Unit at the Bill & Melinda Gates Foundation (2003-2012), overseeing the development and implementation of strategies for the prevention, treatment, and control of diseases of particular relevance to global health, including malaria, pneumonia, diarrhea, and neglected infectious diseases. Dr. Rabinovich has also served in various positions at the U.S. National Institute of Allergy and Infectious Diseases (NIAID), focusing on the development and evaluation of vaccines. She participated in the Children’s Vaccine Initiative, a global effort to prevent infectious diseases in children in the developing world, and served as liaison to the National Vaccine Program Office, focusing on vaccine safety and vaccine research.

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As chief of the Clinical and Regulatory Affairs Branch of the Division of Microbiology and Infectious Diseases, she managed the evaluation of candidate vaccines through a network of U.S. clinical research units. In 1999, Rabinovich became director of the PATH Malaria Vaccine Initiative, a project funded by the Bill & Melinda Gates Foundation to advance efforts to develop promising malaria vaccine candidates. She serves on the boards of several organizations focused on global health and infectious diseases, including the NIAID Council and the NIH Council on Councils; PATH Vaccine Solutions; and AERAS. She is an Advisor to Harvard University’s Defeating Malaria: From the Genes to the Globe Board of Directors. Dr. Rabinovich holds a medical degree from Southern Illinois University and a Masters of Public Health degree from the University of North Carolina.

Mara Riminucci is currently Associate Professor of Pathology at Sapienza University of Rome where she received her MD and PhD degrees. She spent several periods of work at the National Institutes of Health in Bethesda, where she also participated in a clinical protocol on Fibrous Dysplasia of bone as expert consultant. Mara Riminucci has a long-standing interest and experience in bone cell biology and skeletal diseases. Her research activity is especially focused on Fibrous Dysplasia (FD) and skeletal stem cells.

Mara RiminucciAssociate Professor of Pathology Sapienza University of Rome

Innocent SafeukuiResearch ScientistNotre Dame

of Paris (2005-2010). He is currently a Research Scientist at University of Notre Dame (Dr. Kasturi Haldar Lab). His principal field of research is malaria, red blood cell deformability and spleen physiology. He has authored or co-authored 30 articles in peer-reviewed scientific journals and has reviewed several research manuscripts for different journals.

Innocent Safeukui received his PhD in Health-Biology at the University Medical School of Bordeaux II in 2004. He received postdoctoral training at the University Medical School of Bordeaux II (2004-2005) and Institut Pasteur

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Robert W. SauerweinProfessorMedical Parasitology Radboud University Nijmegen Medical Centre

Dr. Sauerwein is an internationally renowned scientist in the field of malaria transmission with an extensive track record in basic and clinical research. He is head of the

Centre for Clinical Malaria Studies (CCMS) in Nijmegen, The Netherlands and full Professor of Medical Parasitology at the Radboud University Medical Center.

Giulia SicilianoPhD CandidateIstituto Superiore di Sanità

Giulia Siciliano is a PhD student at the Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità (Rome, Italy). She obtained a degree in Biological Sciences from the University of

Rome “La Sapienza” working on immunological diseases. After one year as a trainee at the Institute for Research in Biomedicine, Bellinzona, Switzerland, she began working in malaria in 2011, joining the group of Dr. Alano. Her research focuses on genetic approaches to understand the biology of Plasmodium falciparum gametocytes, which are responsible for malaria transmission. Cellular and molecular approaches have been used to identify novel regulatory regions of genes specifically and efficiently activated in late stage of gametocytogenesis of P. falciparum. Despite the recognized beneficial effects on morbidity and mortality of antimalarials targeting also transmission, new assays for screening drugs specifically targeting P. falciparum mature gametocytes are necessary because current published assays based on reporter lines use a limited number of sexual stage specific promoters, mainly active from early through late gametocyte development.

Francesco Maria SilvestriniSenior ResearcherIstituto Superiore di Sanità

Francesco Silvestrini is a Senior Researcher at the Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità in Rome, Italy. He obtained a degree in Biological Sciences at the

University of Rome “La Sapienza” working on genetic and molecular mechanisms involved in mosquito pesticides resistance. He started his research in malaria in

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1994, after having joined the group of Dr. Pietro Alano. Francesco has authored 25

articles in the field of malaria, and his research focuses on genetic approaches to

understanding the basic biology of Plasmodium falciparum gametocytes, which are

largely responsible for malaria transmission. Recent work has lead to the use of

functional genomic approaches and molecular and cellular tools to study the

development of P. falciparum gametocytes. Microarray and proteomic approaches

have been used to characterize the underexplored early stages of P. falciparum

gametocyte development and gametocyte-induced red blood cell changes. This

work enabled the identification of novel P. falciparum gametocyte-specific proteins

and the production of reagents used to investigate gametocyte subcellular

organization. Functional approaches involving production and transfection of gene

fusion constructs are routinely used to study promoter regulation, gene function

and protein subcellular localization in gametocyte development, and molecular,

cellular and biochemical tools are used to analyse developmental processes such as

gamete emergence and gametocyte sequestration. This latter project has recently

been addressed by exploring the mechanical and adhesive properties of sexual

stages in relation with their capability to sequester in specific tissues.

Dr. Smith is an Assistant Professor at Seattle Biomedical Research Institute. He

received a BA in Biology from Macalester College and PhD in Immunology from

Washington University in St. Louis, MO. Dr. Smith completed his postdoctoral

studies at the Laboratory of Parasitic Diseases at NIH. He received a Spencer T. and

Ann W. Olin Medical Scientist Fellow awarded in recognition of superior

achievement in biomedical research (1993), New Investigator Award from the

National Foundation for Infectious Diseases (2000), and New Scholar in Global

Infectious Disease Award from the Ellison Medical Foundation (2001). He is an

Associate Editor at PLoS Pathogens and on the editorial board at Eukaryotic Cell

DQG�KH�VHUYHG�RQ�WKH�3DWKRJHQLF�(XNDU\RWHV��37+(��6WXG\�6HFWLRQ�ɾ�+LV�UHVHDUFK�focuses on the biology of cytoadhesion of Plasmodium falciparum infected

erythrocytes.

Joseph SmithAssistant Professor

Seattle Biomedical Research Institute

Colin SutherlandReader in Parasitology

Head, Department of Immunology and Infection

London School of Hygiene & Tropical Medicine

Dr. Sutherland joined the London School of Hygiene and

Tropical (LSHTM) Medicine in January 1998 as a

Research Fellow to work with Professor Geoffrey Targett on the adhesion of

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Plasmodium falciparum gametocytes. Colin coordinated a series of Wellcome Trust-funded clinical trials which measured the effect of antimalarial combination therapy on transmission of P. falciparum in Farafenni, The Gambia from 2000 to 2002. This led further work focussed on parasite drug resistance in many African countries funded by the Gates Malaria Partnership from 2000 – 2008, and the EU FP& MALACTRES Project from 2008 – 2013. Since 2004 Colin has been supported by the Health Protection Agency (HPA) and has a joint appointment in the HPA Malaria Reference Laboratory in LSHTM, and the Department of Clinical Parasitology, Hospital for Tropical Diseases (HTD), where he is engaged in studies of the genetics/genomics of drug sensitivity in all Plasmodium species that infect humans. The Sutherland research group in the Department of Immunology and Infection at LSHTM comprises 4 PhD students, 3 Post-docs and 1 Technician, and has current research projects on: 1) the genetics & epidemiology of ovale malaria; 2) use of LAMP technology as a tool for malaria elimination; 3) genetic polymorphisms in P. falciparum associated with resistance to ACT drugs in vivo; and 4) in vitro drug responses and genome variation in isolates of P. falciparum, P. malariae and P. ovale.

Donatella TaramelliProfessor of Pathology, Faculty of Pharmacy University of Milan

Donatella Taramelli is Full Professor of Pathology in the Faculty of Pharmacy of the University of Milan, Milan, Italy since 2000. She is also the Director of the Graduate

School in Pharmaceutical Biotechnology. After obtaining a degree in Biology, Professor Taramelli completed her post-doctoral training in the Lab of Immunodiagnosis, NCI, NIH, Bethesda, MD and then at the National Cancer Institute in Milan, Italy. In 1987, she became Associated Professor of Pathology and Microbiology affiliated to the Medical School and, in 1993, to the Faculty of Pharmacy of the University of Milan. Professor Taramelli’s bibliography includes 135 PubMed indexed papers, 16 book chapters, and one international patent. The main research areas of her group include antimalarial drug screening against different P. falciparum stages; studies on the mechanism of action of quinoline andartemisinin antimalarials including SAR analysis; and studies on parasite-host relationships. In particular, she studies the effects of parasite products, namely hemozoin, on the host innate immune response and on endothelial cells adhesiveness and activation. She also investigated the effects of antimalarial drugs on angiogenesis and human erythroid differentiation in relationship to malaria anemia.

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Leann TilleyProfessor and Deputy HeadDepartment of Biochemistry & Molecular Biology Bio21 Molecular Science & Biotechnology InstituteUniversity of Melbourne

In the late 80s, Dr. Mauro Valtieri was involved in the search for human granulocyte colony-stimulating-factor (G-CSF) which, later on, became an important tool to maintain white blood cell count in cancer patients. About the same time he established a number of primary leukemia cell lines, which, since then, have been widely utilized to isolate many leukemia genes and discern other leukemia abnormalities. Interestingly, in 1991, he published an article where he combined retinoic acid and G-CSF to induce granulocytic differentiation in a leukemic cell line, or vitamin D3 plus M-CSF to induce monocytic differentiation of the same leukemic line. Between Philadelphia and Rome, he worked with several oncogenes, namely (BCR/)abl, myc, h-ras, c-kit, TAL1/SCL, PML(/RAR alpha), and tumor-suppressors, i.e. Rb, Fhit, PP2A, for their contribution to acute and chronic leukemias, and lung cancer, also utilizing retroviral and lentiviral vectors. In addition, he has contributed to the understanding of hematopoiesis and hematopoietic stem cells, whose maintenance is paramount during cancer and cancer treatments, often leading to severe pan-cytopenias. Lately, he isolated and characterized mesenchymal stem cells from bone marrow, in addition to different

Leann Tilley is an ARC Australian Professional Fellow and Director of the Australian Research Council Centre of Excellence for Coherent X-ray Science (CXS). Professor Tilley’s group undertakes research in the areas of cell biology and drug development related to the malaria parasite, Plasmodium falciparum. Her lab investigates the mechanisms of action of and resistance to the antimalarial drug, artemisinin, with a view to designing better antimalarials. She is also interested in the unusual protein trafficking pathways that the malaria parasite uses to display virulence proteins at the erythrocyte surface, and in understanding the molecular basis for the remarkable transformation that allows the malaria parasite to be transmitted from a human host to a mosquito vector. Leann’s laboratory has helped to develop and implement a number of new imaging modalities and to apply them in pioneering applications. These include super-resolution optical microscopy and whole cell electron tomography.

Mauro ValtieriAdjunct Professor, Temple University, Sbarro Institute for Cancer Research and Molecular Medicine & Center of BiotechnologyDirector, Stem Cell Center, Department of Hematology, Oncology & Molecular Medicine Istituto Superiore di Sanità

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human tissues, always taking in consideration their hematopoietic supportive function, and has focused also on colonic mesenchymal stem cells and their role in Crohn’s disease and colon cancer. The overall scientific production of MV counts 72 manuscripts (from PubMed), some of which extensively cited.

Sarah VolkmanPrincipal Research ScientistDepartment of Immunology & Infectious Diseases, Harvard School of Public HealthMember and DirectorMalaria Diversity Project, Broad InstituteProfessor of Nursing Simmons College

Sarah Volkman has over twenty years of experience in malaria biology and is a world expert on malaria with a focus on mechanisms of drug resistance. Her primary research interest centers on understanding genetic variation in Plasmodium falciparum, a causative agent of human malaria infection, and employing population genetic strategies to identify genetic loci that contribute to drug resistance in this organism. She is currently working toward the development of a genetic Diversity Map for P. falciparum that may ultimately be used to associate genetic polymorphisms with biologically and clinically relevant phenotypes. Sarah received her B.S. from the University of California, San Diego (cum laude) in 1986 and her Sc.D. from the Division of Biological Sciences at the Harvard School of Public Health in 1995. She conducted postdoctoral studies with Professor Dyann Wirth at the Harvard School of Public Health and was appointed

Omar VandalProgram Officer, Drug DiscoveryBill & Melinda Gates Foundation

Omar Vandal joined the Bill & Melinda Gates Foundation Drug Discovery team in 2010. As a Program Officer he is involved in developing and

managing early-stage discovery investments in TB, malaria, and the Grand Challenges programs. Omar received his PhD in 2007 from the Weill Cornell Graduate School of Medical Sciences in New York, where he trained in immunology and microbial pathogenesis in the laboratories of Drs. Carl Nathan and Sabine Ehrt. His graduate and post-doctoral work at Cornell focused on understanding interactions of Mycobacterium tuberculosis with the host and the identification of new drug targets for the treatment of TB. From 2008 – 2010 Omar worked at the Global Alliance for TB Drug Development (TB Alliance) in New York.

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senior research scientist in 1998. Sarah Volkman is a molecular biologist and senior research scientist in the Department of Immunology and Infectious Disease at the Harvard School of Public Health. She is a member of the Broad Institute and Director of Institute’s Malaria Diversity Project. Dr. Volkman is also a Professor of Nursing at the School for Health Studies at Simmons College where she has been involved in preparing nursing students in the basic science content since 1989. She teaches Normal and Abnormal Physiology as well as the Integrative Sciences Curriculum for the Direct Entry Program including Biochemistry, Microbiology, and Anatomy and Physiology. In addition to her teaching and research interests, Dr. Volkman is currently writing a textbook on human pathophysiology, which uses clinical case scenarios to examine the mechanisms of human disease. She has received several awards including the Young Investigator Award by the American Society of Tropical Medicine and Hygiene, and was a Senior Teaching Fellow at Harvard University. She is also a member of the Scientific Advisory Committee for the WorldWide Antimalarial Resistance Network (wWARN) and a member of the Malaria Disease Reference group of TDR.

Professor von Andrian's research seeks answers to the question how circulating blood cells find their way in the body. Directed migration of blood-borne cells to distinct target tissues can be observed in embryos as soon as the circulatory system is established and plays a critical role throughout life in numerous physiologic and pathologic conditions. Despite considerable progress in this field, it is still beyond the reach of even the most sophisticated in vitro methodology to simulate the complex interplay of physical, cellular, biochemical, and other factors that determine blood cell behavior in microvessels. Therefore, his lab employs intravital microscopy to study the molecular mechanisms of interactions between blood cells and the vascular wall by direct observation in anesthetized mice. Using this approach, they have demonstrated that blood cell homing to most target tissues requires an initial tethering step that leads to rolling in postcapillary venules and is followed by an activation step which, in turn, triggers stationary adhesion and emigration. Each of these three steps (i.e. 1. rolling; 2. chemotactic stimulation; and 3. firm arrest) involves distinct molecular pathways whose unique combination is the reason why certain blood cells migrate to a particular organ, whereas others don't. They are now dissecting the site-specific adhesion cascades that direct myeloid and lymphoid cells, hematopoietic stem cells and platelets to normal and diseased tissues. They have established models in mice that allow quantitative observations in Peyer's patches; gut; bladder; striated muscle; skin; pancreas; liver;

Ulrich H. von AndrianEdward Mallinckrodt Jr. Professor of Immunopathology Department of Microbiology & ImmunobiologyHarvard Medical SchoolSenior InvestigatorBoston Children’s Hospital

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knee joint; bone marrow; bone; and peripheral lymph nodes. The techniques for

observing the latter three tissues were developed in the von Andrian laboratory.

Understanding how lymphocytes, in particular T cells, home to and migrate within

peripheral lymph nodes is a major focus of his group. To this end, they are using a

panel of mice that are genetically deficient in specific adhesion pathways. They have

also generated transgenic mouse strains that express fluorescent proteins in

distinct T cell subsets. They are using these mice to study how T cells differentiate

into effector and memory subsets; how this differentiation affects their migratory

properties; and how antigen-presenting dendritic cells influence these processes. T

cells and dendritic cells can be visualized in the intra- and extravascular space by

intravital microscopy using both single- and multi-photon fluorescence techniques.

This allows them to dissect the trafficking behavior of these immune cells at a

resolution and specificity that could not be achieved with other methods. Besides

supervising and instructing the students and fellows in his laboratory (15-20

members), Professor von Andrian's current teaching activities include the

co-direction and organization of the Immunology 201 and Immunology 202

semester courses for HMS graduate students. In addition, they have numerous

collaborators in the Harvard community and elsewhere who perform intravital

microscopy studies in their facility under Professor von Andrian's supervision. He

also lectures regularly to HMS graduate students, postdoctoral fellows and staff

about leukocyte adhesion, migration and homing.

Andy WatersDirector, Wellcome Centre for Molecular

Parasitology, University of Glasgow

Director, European Virtual Institute for Malaria

Research

Andy Waters is Director of the Wellcome Centre for

Molecular Parasitology at the University of Glasgow, a position assumed in mid-

�����ɾ+H� LV�DOVR�'LUHFWRU�RI� WKH�(XURSHDQ�9LUWXDO� ,QVWLWXWH� IRU�0DODULD�5HVHDUFK�(EVIMALAR), a European Commission-funded Network of Excellence that links

!���PDODULD�UHVHDUFK�ODERUDWRULHV�FKLHIO\�DFURVV�(XURSH�DQG�$IULFD�ɾ+H�UHWXUQHG�WR� Glasgow in 2008 as a Wellcome Trust Principal Research Fellow and Professor of

Molecular and Developmental Parasitology. Prior to this he spent 16 years at the

Leiden University Medical Centre achieving the rank of Professor in 2004. He has

30 years of experience in malaria research, the majority of the time spent working

with the rodent malaria model, Plasmodium berghei�ɾ+H�KDV�SOD\HG�D�FHQWUDO�UROH�in the development of genetic manipulation of malaria parasites and helped

GHYHORS�WKH�LQLWLDO�V\VWHPV�IRU�WKLV�SXUSRVH�ɾ7KHVH�KDYH�EHHQ�VXEVHTXHQWO\�DSSOLHG�to many questions but principally his interests have centred on the development of

the blood stage forms of the malaria parasite responsible for transmission to

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Dyann WirthRichard Pearson Strong Professor of Infectious Diseases and ChairDepartment of Immunology & Infectious DiseasesHarvard School of Public Health

Professor Wirth has been a major leader in the area of malaria research. Her work has provided completely new insight into how the malaria parasite has evolved, specifically in the areas of population biology, drug resistance and antigenicity. The Wirth laboratory blends the scientific environments of the Harvard School of Public Health, the Broad Institute, and collaborators from around the globe to create a unique malaria research and training network that brings together scientists with expertise in molecular biology, genetics, genomics, population genetics, chemistry, cell biology, epidemiology, computational biology, biostatistics, and leading clinicians in infectious diseases and pathology. Using this approach, the Wirth group is working to understand the mechanisms of drug resistance in Plasmodium falciparum, the major human malaria parasite. Leveraging the genomic tools of the human genomic project, the group has applied state of the art technologies and novel approaches to better understand the fundamental biology of the malaria parasite and mechanisms of drug resistance. Professor Wirth’s research activities are made possible through collaborative research partnerships with investigators, universities, and clinical centers in Africa, Asia, Central and South America. Together with partners in the malaria community, she is involved in a new academic effort at Harvard University to produce, transmit, and translate knowledge to support the control and ultimate eradication of malaria. The Defeating Malaria: From the Genes to the Globe initiative is a University-wide effort that is spearheaded by the Harvard School of Public Health in collaboration with the Harvard Global Health Institute, and in partnership with the United Nations Special Envoy for Malaria. She is Past President of the American Society of Tropical Medicine and Hygiene; a member of the Board of Directors of the Burroughs-Wellcome Fund and the Board of the Marine Biological Laboratory; she is also a member of The Institute of Medicine of the National Academy of Sciences and a Fellow of the American Academy of Microbiology.

the mosquito and their subsequent development in the mosquito midgut.

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Sulin ZhangAssociate ProfessorDepartment of Engineering Science & Mechanics Department of Bioengineering Pennsylvania State University

Dr. Sulin Zhang received his PhD from the University of Illinois, Urbana-Champaign in 2002. He is currently an Associate Professor in the Engineering Science and Mechanics at Penn State University (PSU) and an affiliated faculty in the Department of Biomedical Engineering of PSU. Dr. Zhang’s research interests include multiscale modeling and experimental characterization of nanostructured and bio-inspired materials, and of processes that occur at nano-bio interfaces. He is particularly interested in the role of mechanics in biology. He and his collaborators developed a coarse-grained molecular model of red blood cell that is suited to uncover molecular mechanisms of red blood cell disorders, including malaria. His group has also been pioneering in the study of the governing factors for the cellular uptake of nanoparticles. Dr. Zhang is the recipient of the Oak Ridge Ralph E. Powe Junior Faculty Enhancement Award in 2006, and the Early Career Development Award from National Science Foundation in 2007.

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Generous financial and technical support has been provided by the following sponsors:

Front cover image: Scanning electron microscopy images of P. falciparum gametocyte infected erythrocytes from stage II to V of maturation. A switch in infected erythrocyte deformability at the maturation and blood circulation of Plasmodium falciparum transmission stages. Blood 119(24):e172-80. Image courtesy of Sylvie Perrot and Catherine Lavazec, Institut Pasteur, in Tiburcio et al. (2012). Special thanks for image editing to Sandra Nilsson, Harvard School of Public Health.

Acknowledgements