Faculty John Treanor, M.D. Professor of Medicine and Professor of Microbiology and Immunology Department of Medicine Division of Infectious Diseases Human immune responses to influenza virus, and clinical vaccine trials John Treanor, M.D. is the Director of the New York Center of Excellence and leads the clinical core. He received his medical degree in 1979 from the University of Rochester and fellowship in Infectious Diseases at the University of Rochester. Dr. Treanor is currently Professor of Medicine, Microbiology, and Immunology, and Chief of the Infectious Diseases Division at the University of Rochester Medical Center. Dr. Treanor has a long-standing interest in clinical research on influenza and vaccine development, and has been particularly involved in the clinical development of potential live vaccines for pandemic influenza. Dr. Treanor directs the activities of the clinical core, including designing studies to assess the immune response to infection and vaccination, and assessing population immunity to pandemic threat viruses. David Topham, Ph.D. Associate Professor of Microbiology and Immunology David H Smith Center for Vaccine Biology and Immunology T cell responses to influenza virus infection The specter of a pandemic caused by avian influenza virus highlights the need to identify possible mechanisms of immune protection from emerging strains of the flu virus. We cannot accurately predict which influenza will emerge as the next pandemic, making it difficult to select and manufacture sufficient conventional vaccine to elicit protective homotypic antibodies. Protective T cell mediated heterosubtypic immunity to influenza is an established paradigm in animal models, but is not well documented in humans. Though it is likely that heterosubtypic immunity to influenza exists in humans, there is little evidence of its specificity, and the reasons why it may or may not be protective are unclear. Our lab has shown that optimal CD8 T cell mediated heterosubtypic immunity is provided when T cells are retained in the lung tissue and airways via their interaction with collagen via the VLA-1 collagen receptor (Ray et al., 2004). One hypothesis is that heterosubtypic immunity to influenza fails in humans because of insufficient memory in the lung tissue. Having these T cells in place would not prevent infection, but could limit the duration and magnitude of viral replication. This could be the difference between life and death when encountering an emerging pandemic strain of influenza. Conventional influenza subunit vaccination is designed to generate antibodies, and does not strongly stimulate tissue-memory. Future strategies for influenza vaccine design should target both antibodies and cross-reactive lymphoid and tissue memory T cells. Our goals are to better understand potentially heterosubtypic immune responses to influenza and begin to develop the means to evaluate and, in the future, promote optimal vaccination strategies. To accomplish these goals, the Topham lab has established assays for detailed analysis of cell-mediated immunity (CMI) against influenza in humans, and has developed improved animal models for studying CD4 T cell mediated influenza immunity in mice. Comprehensive assay systems are established to target CD4 and CD8 T cells, and B cells responding to influenza virus, viral hemagglutinin, or influenza vaccines. Andrea J. Sant, Ph.D. Professor of Microbiology and Immunology David H Smith Center for Vaccine Biology and Immunology Immunodominance of CD4 T cell responses to influenza virus Dr. Sant received her Ph.D. in Immunogenetics from Washington University in St. Louis in 1985. She currently Professor of Microbiology and Immunology at the University of Rochester. The research in Dr. Sant’s laboratory centers around the molecular events that regulate MHC class II- restricted antigen presentation of influenza proteins by antigen presenting cells (APC) and CD4 T cell recruitment in vivo. Dr. Sant will lead project 3, focused on the CD4 response to infection and vaccination, and the potential impact of CD4 peptide specificity on the development of B cell responses specifically to the HA protein. Patrick C. Wilson, Ph.D. Dr. Wilson received his Ph.D. in Immunology from the University of Texas Southwestern Medical Center in 2000, and post- doctoral training in the Nussenzweig lab at The Rockefeller University in New York City. He currently serves as Associate Professor with tenure in the Department of Medicine/Rheumatology,at the University of Chicago. Dr. Wilson’s interests include the development of technology to clone recombinant monoclonal antibodies from discreet populations of B cells. Dr. Wilson will lead Project 2 focused on the B cell response to infection, as well as providing monoclonal antibodies he has, and cloning additional human antibodies specific for influenza HA and NA glycoproteins. Hana Golding, Ph.D. Dr. Golding will assist with studies conducted under project 1. Dr. Golding received her Ph.D. in Immunology from Oregon Health Sciences University in 1981, and completed post-graduate work as a Visiting Fellow under Dr. Alfred Singer in 1985 at the Immunology Branch, NCI, NIH, and then as a Visiting Associate in the same branch under Dr. Dinah Singer in 1987. She joined the Food and Drug Administration in 1989, and since 1993 she has served as Chief of the Laboratory of Retrovirus Research in the Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA). She will lead the experiments in Aims 1 and 2 of Project 1 to perform Gene Fragment Phage Display Library (GFPDL) studies of antibody specificity, a technique that she pioneered for use in influenza. Surender Khurana, Ph.D. Dr. Surender Khurana will assist in the conduct of studies in project 1. Dr. Khurana received his Ph.D. in Biochemistry in 2002 from Delhi University, India. He has been at the Food and Drug Administration since 2002, where he currently serves as Staff Scientist in the Division of Viral Products, Center for Biologics Evaluation and Research (CBEM). His research interests are focused on developing new molecular tools for better understanding of how different vaccine modalities and novel adjuvants improve protective immunity against influenza. Dr. Khurana developed the Surface Plasmon Resonance (SPR) assays which will be used in project 1. Masanori Terajima, M.D., Ph.D. Dr. Terajima received his M.D. in 1988 and his Ph.D. in Developmental Biology in 1994, both from Tohoku University School of Medicine in Japan. Dr. Terajima is a Graduate Faculty Member and Associate Professor of Medicine at the University of Massachusetts Medical School. His research interests include immune responses to influenza virus infection and vaccination, and particularly the development of ADCC and CDL antibody responses. Dr. Terajima will be involved in focusing on molecular and developmental aspects of the CDL and ADCC antibody studies proposed in project 2. Michael Katze, Ph.D. Dr. Katze will lead studies to evaluate the innate immune response to influenza vaccine and infection. Dr. Katze is Professor of Microbiology and Associate Director at the Washington National Primate Research Center at the University of Washington. His research focuses on using systems biology approaches to define and model virus-host interactions, innate immune signaling, and the strategies used by viruses to evade cellular defense mechanisms. He has studied influenza virus for over 30 years and has pioneered the use of genomic methods in mouse, ferret, and nonhuman primate models of pandemic and highly pathogenic avian influenza virus infection. Gary R. Whittaker, Ph.D. Dr. Whittaker received his Ph.D. in Microbiology from the University of Leeds in 1991, and completed a postdoctoral fellowship in Cell Biology at Yale University. He is currently Professor in the Department of Microbiology and Immunology at Cornell University. His research interests include the cell biological and biochemical aspects of virus entry, and how virus entry pathways relate to viral pathogenesis. will assist with sequencing of the influenza virus genomes from the surveillance studies, and help interpret data in the context of HA antigenicity. He will direct experiments to assess the potential impact of bacterial coinfection on the evolution of the influenza HA cleavage site. Luis Martínez-Sobrido, Ph.D. Dr. Martínez-Sobrido received his Ph.D. in Virology and Molecular Biology in 2000 from the Instituto de Salud Carlos III and completed Postdoctoral training at Mount Sinai School of Medicine. He is currently Assistant Professor. He is interested in the use of plasmid-based reverse genetics techniques to rescue recombinant influenza viruses. He will construct recombinant single cycle influenza viruses for assessment of immunity. Mark Y. Sangster, Ph.D. Research Associate Professor David H Smith Center for Vaccine Biology and Immunology Dr. Sangster received his Ph.D. in Virology/Genetics from the University of Western Australia in 1991. He then completed postdoctoral work in Immunology at St. Jude’s Children’s Research Hospital. Dr. Sangster is an expert in the analysis of B cell responses to infection and vaccination. His major interests have been mucosal aspects of B cell responses in the respiratory tract and the nature of virus-specific B cell memory. He will perform studies of mucosal antibody and B cell responses, and B cell memory. Peter G. Szilagyi, M.D., M.P.H. Dr. Szilagyi received his medical degree in 1981 from the University of Rochester and completed his M.P.H. in 1987, also from the University of Rochester. He is a Professor of Pediatrics at the University of Rochester and chief of General Pediatrics. Dr. Szilagyi serves as Director of the Greater Rochester Practice-Based Research Network, a unique network of private practice clinical sites engaged in clinical and translational research. He will serve as the lead investigator of expanded surveillance studies and assessment of disease impact. Hulin Wu, Ph.D. Dr. Wu is Dean’s Professor of Biostatistics and Computational Biology and Professor of Medicine (Infectious Diseases Unit) at the University of Rochester Medical Center. Dr. Wu is internationally known for his research in developing novel statistical and bioinformatics methodologies for immunology and infectious diseases. Dr. Wu will be responsible for overseeing and co- directing the operations and activities of the Data Management, Bioinformatics and Biostatistics Core at the Rochester site. Jeanne Holden-Wiltse, M.P.H. Ms. Holden-Wiltse received her MPH from University of Michigan School of Public Health in 1991, and has over 17 years of experience in biostatistical support having held positions in industry, government, not-for-profit organizations and academia. Ms. Holden-Wiltse will act as Co-Leader of the Data Management, Bioinformatics and Biostatistics Core. Doreen M. Francis, R.N., C.C.R.C Ms. Francis received her R.N. in 1973 from the Highland Hospital School of Nursing. She currently serves as Research Administrator and Coordinator for the Vaccine Research Unit in the Infectious Diseases Division at the University of Rochester. Ms. Francis is a highly experienced clinical research coordinator, and she will oversee regulatory and operational aspects of clinical research conducted by NYICE. Donna Neu, PMP Ms. Neu received her B.A. in Computer Science from the State University of New York at Oswego in 1986, and her PMP from the Project Management Institute in 2005. She is currently Project Manager of the New York Influenza Center of Excellence, and the Respiratory Pathogens Research Center at UR. As Project Manager, Ms. Neu will oversee day to day operations of NYICE and coordinate interactions between other CEIRS centers, NYICE and contract operations.