Edward S Mocarski, PhD
Emory Vaccine Center
Robert W. Woodruff Professor
Department of Microbiolgy and Immunology, Emory University School of Medicine
Distinguished Cancer Scholar
Georgia Cancer Coalition
Edward S. Mocarski, Jr. received an A.B. from Rutgers University in 1974 and a Ph.D. from the University of Iowa in 1979, both degrees in microbiology. He completed a postdoctoral fellowship in virology at The University of Chicago with Dr. Bernard Roizman in 1982. Dr. Mocarski joined Stanford University in 1983 and was Chairman of the Department of Microbiology and Immunology and Professor of Microbiology and Immunology at Stanford University School of Medicine as well as Associate Dean of Research within Stanford University’s Provost’s Office. He retired from Stanford and became Professor Emeritus when he joined the faculty at Emory University School of Medicine in 2006 as Robert W. Woodruff Professor in the Department of Microbiology and Immunology and the Emory Vaccine Center. He was Distinguished Fellow at MedImmune, LLC, where he managed an expansion of vaccine pipeline research with particular attention to herpes viruses, including cytomegalovirus. He returned to Emory as a full-time faculty member in 2011.
Edward S. Mocarski, Jr.
Robert W. Woodruff Professor
Georgia Cancer Coalition Senior Scholar
Department of Microbiology and Immunology (2006 – present)
Emory University Vaccine Center
Emory University School of Medicine
Atlanta, GA 30322
MedImmune Distinguished Fellow (Nov 2008 – Jan 2011)
Professor Emeritus Stanford University (1983 – 2006)
Over the most recent decade my laboratory has focused on the infected cell response to infection, mainly the contribution of regulated cell death pathways to host defense. The phenomenal diversity of CMV-encoded modulators of the host response to infection provided an opening, with the cell death suppressors, which have been conserved in human and murine CMV, evolved as separate pathogens, contributing handily to the knowledge base. We recently discovered that caspase 8 can be eliminated from the mouse germ line, most likely because this protease evolved in mammals under the adaptive pressure of large viruses that encode suppressors of mitochondrial apoptosis. Our characterization of receptor interacting protein (RIP)3 kinase-dependent programmed necrosis as a “trap door” that opens when caspase 8 activity is compromised points to a multi-level and complementary contribution of programmed cell death pathways to host defense. These efforts show that CMV-encoded viral inhibitor of caspase 8 activation (vICA) and viral inhibitor of RIP activation (vIRA) block caspase-dependent apoptosis and RIP3-dependent necrosis, respectively. In the absence of vIRA, the pathogen sensor DAI senses input viral DNA and then oligomerizes with RIP3 to initiate programmed necrosis that eliminates infected cells. We have established that vICA suppression of caspase 8 activity is an essential part of this process, and that, together, vICA and vIRA represent key modulators of potent host defense pathways. These insights prompted our discovery that embryonic lethality due to germline deficiency in caspase 8 results from dysregulated RIP3 kinase-dependent necrosis. Because CMV is such a master manipulator of the host response to infection, other individual viral gene products have provided us with high impact observations, such as the virus-encoded chemokine whose function assures CMV-susceptible myeloid cells are recruited to sites of infection as vehicles for dissemination as well as to downmodulate the CD8 T cell response to infection. Over the years, the multiple, incisive contributions I have made to understanding of herpesvirus replication functions, characterization of the latent CMV reservoir in myelomonocytic progenitors, dissection of immunomodulatory pathways including the cellular response to viral infection as well as our most recent mechanistic studies focused on complementary and overlapping viral and host pathways provide ample evidence of scientific leadership.
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