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Michael S. Diamond, MD, PhD
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Michael S. Diamond, MD, PhD Associate Professor, Departments of Medicine, Molecular Microbiology, Pathology & Immunology Office Location: 7264 McDonnell Pediatric Research Building Dr. Diamond joined Washington University in 2001. He received his M.D. and Ph.D. degrees from Harvard Medical School and Harvard University. He completed his post-doctoral training at the University of California, Berkeley, and his internship, residency, and fellowship in infectious diseases at the University of California, San Francisco. His current research focuses on the interface between viral pathogenesis and the host immune response. Three globally important human pathogens are studied, West Nile encephalitis, dengue hemorrhagic fever, and hepatitis C viruses. Research Interests The research in the Diamond laboratory focuses on the interface between viral pathogenesis and the host immune response. For several years, we have been primarily focused on two globally important mosquito-borne human pathogens West Nile virus and Dengue virus. Both are single-stranded positive-sense RNA viruses of the same genus (Flavivirus) that cause human disease worldwide. Recently, we have begun to study another member of the same virus family, hepatitis C, which causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Investigations with hepatitis C virus are aimed at generating a novel mouse model and understanding the epitope specificity of protective antibodies against this virus. To date, studies with West Nile and Dengue viruses have focused on investigating their pathogenesis and the immune system response that controls infection. Using in vitro models of infection in primary neurons, macrophages, and dendtitic cells, we are studying the mechanisms by which West Nile virus causes direct injury to specific cell types, and how the host responds to limit viral replication. Using a mouse model we have defined critical roles for interferon, antibody, complement, CD4+, and CD8+ cell in the control and eradication of West Nile virus infection. We have begun to study the structural and molecular basis of antibody-mediated protection of West Nile and Dengue virus. By combining our structural and pathogenesis data, we have developed a single monoclonal antibody that has strong therapeutic activity against WNV even after the virus has disseminated into the central nervous system. A humanized form of this antibody is currently in human clinical trials for the treatment of acute West Nile virus. This data is also being applied to the development of novel strategies for vaccine development. New directions in the Diamond laboratory include understanding how the immune response restricts West Nile virus diversity and fitness, the role of cholesterol in regulating flavivirus infection, mechanisms of immune evasion by Dengue and West Nile virus. In addition, our most recent studies with the complement opsonin C1q suggest new insight into understanding the conditions in which antibodies enhance Dengue virus replication during secondary infection.
Division of Infectious Diseases
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