Michael S. Diamond, MD, PhD
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 severe encephalitis and hemorrhagic fever, respectively, in humans and related to a group of viruses 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 as well as an emerging alphavirus, Chikungunya virus. Investigations with hepatitis C and Chikungunya viruses are aimed at understanding the epitope specificity of protective neutralizing antibodies against these viruses. To date, studies with West Nile and Dengue viruses have focused on investigating their pathogenesis and the immune system response that control infection. Using in vitro models of infection in primary neurons, macrophages, and dendritic cells, we are also 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, interferon-stimulated genes, antibody, complement, CD4+, and CD8+ T cells in the control and eradication of West Nile virus infection. Other directions in the Diamond laboratory include understanding how novel innate immune response effector molecules restrict infection of flaviviruses and alphaviruses, systems biology approaches to dissecting innate immunity in the brain, how the innate immune system contributes to the establishment and maintenance of memory B and T cell responses, and how these processes are affected by aging.