Mark Heise, Ph.D
Professor, UNC Chapel Hill
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This Morning we interviewed Dr. Heise
Dr. Mark Heise received his BA in biology from St. Olaf College, Northfield, MN in 1991 and performed his graduate work in the laboratory of Dr. Herbert “Skip” Virgin at the Washington University School of Medicine. The focus of his research was on virus host interactions/viral pathogenesis, with an emphasis on immune evasion by murine cytomegalovirus. He received his Ph.D. in 1997 and then went on to perform his postdoctoral studies in the laboratory of Dr. Robert Johnston, at the University of North Carolina at Chapel Hill, where his work focused on the molecular virology and pathogenesis of mosquito borne viruses. In 2000 he joined the faculty at UNC as a Research Assistant Professor in the Department of Microbiology and Immunology, and in 2003 moved to the Department of Genetics, with a joint appointment in Microbiology and Immunology at the rank of Assistant Professor and is a founding member of the Carolina Vaccine Institute.
The Heise lab’s main research focus is on viral pathogenesis, with the goal of achieving a comprehensive understanding of the role that viral and host genetic variation plays in determining the outcome of virus induced disease processes. This work takes advantage of several novel viral pathogenesis models, where we have developed panels of genetically defined viruses of varying virulence, as well as mouse models that allow us to evaluate the role of specific host genes, or sets of genes in regulating disease outcome. This work is primarily focused on the pathogenesis of alphavirus-induced arthritis, where we are studying the mechanisms by which arthritic alphaviruses modulate the host immune response to establish infection and induce inflammatory arthritis. However, we have also recently begun extending this work to respiratory pathogens, such as influenza and SARS coronavirus, in collaboration with Ralph Baric’s laboratory in the UNC School of Public Health. This research can be broken down into three major areas: 1) Identification of mechanisms that pathogenic alphaviruses utilize to avoid the host innate immune response, 2) Evaluation of the role that specific host pathways play in the pathogenesis of alphavirus-induced arthritis and SARS CoV-induced respiratory disease, and 3) Identification of host genetic loci that contribute to resistance or susceptibility to viral pathogens, with the ultimate goal of using all of this information to develop improved vaccines or therapeutics for at risk populations.
Our work on immune evasion has defined a novel viral evasion strategy, where the presence of high mannose glycans on the virus that is delivered by the mosquito enables the virus to avoid the induction of an antiviral type I interferon response in dendritic cells, which are the initial target of viral replication following delivery from the mosquito. This work has led us to begin evaluating the role of host C-type lectins in regulating anti-viral immune responses both in vitro and in vivo. Additional work has also defined roles for the alphavirus nonstructural proteins in regulating the host type I IFN response, both by limiting the ability of the viral RNA to act as an inducer of type I IFN, and by actively antagonizing the ability of the host cell to either produce a type I IFN response or respond to type I IFN. We anticipate that this work will not only lead to the identification of novel mechanisms of immune evasion, but will also significantly enhance our understanding of the mechanisms by which mosquito-borne alphaviruses establish infection and cause disease.
We are also using in vivo models of virus-induced disease to study the role of specific host immune pathways in the pathogenesis of virus-induced arthritis. This work has defined a novel role for the host complement cascade and specifically the mannose binding lectin pathway of complement activation in driving Ross River virus-induced disease in the mouse model, and studies are currently underway to determine whether these pathways also contribute to disease resistance/susceptibility in humans suffering from alphavirus-induced arthritis. In collaboration with the laboratory of Ralph Baric, we have also demonstrated that the complement cascade contributes to SARS-CoV induced disease in the mouse, while MyD88, an adaptor protein required for Toll-like receptor and IL/IL18 receptor signaling, is required for resistance to SARS-induced disease. This work, which is significantly enhancing our understanding of the contribution of host innate immune pathways to susceptibility or resistance to virus-induced disease, may ultimately lead to the development of new therapies for virus-induced arthritis or respiratory pathogens.
Laboratory Publications of Interest for Glycomics:
Morrison, T.E., R.J.Fraser, P.N. Smith, S. Mahalingam, and M. T. Heise. 2007. Complement contributes to inflammatory tissue destruction in a mouse model of Ross River virus-induced disease. Journal of Virology. 81: 5132-5143
(Selected for Journal of Virology Spotlight) PMID: 17314163
Shabman, R.S., T.E. Morrison, C. Moore, L. White, M.S. Suthar, L. Hueston, N. Rulli, B. Lidbury, J. P-Y. Ting, S. Mahalingam, and M.T. Heise. 2006. Differential Induction of Type I IFN Responses in Myeloid Dendritic Cells by Mosquito and Mammalian cell-derived Alphaviruses, Journal of Virology. 81:237-247 PMID: 17079324
