John Misasi, M.D.
|Title||Instructor in Pediatrics|
|Institution||Children's Hospital Boston|
300 Longwood Ave
Boston MA 02115
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2008||Sanofi-Pasteur Pediatric Infectious Diseases Society Fellowship Award|
2008||Maxwell Finland Award for Excellence in Research|
2009||K12-Children’s Health Research Center Scholar|
Dr. Misasi's research is focused on the entry mechanisms of the hemorrhagic fever viruses belonging to the Filoviridae and Arenaviridae families. Ebola and Lassa are two members of these virus families and cause hemorrhagic fever in Africa. Ebola causes sporadic outbreaks of severe infection in central Africa; Lassa occurs in West Africa, infecting >100,000 people and killing up to 5000 people annually.
Ebola and Lassa are both enveloped negative strand RNA viruses. Each virus expresses a protein, GP, on the surface of its envelope. This protein, GP, is required for the virus to enter and infect the cell. The interactions between GP and host cells that allow these viruses to enter a cell are the focus Dr. Misasi’s research. Previous research has demonstrated that the digestion of Ebola GP by the proteases Cathepsin B and Cathepsin L is required for Ebola entry. Dr. Misasi’s demonstrated that there are other cysteine proteases that are likely to contribute to Ebola virus entry and that there is a species dependent difference in cysteine protease usage among the different species of Ebola viruses. In addition to this work, Dr. Misasi identified novel inhibitors of Ebola virus entry using a small molecule library screen. He used these inhibitors to identify Niemann-Pick disease, type C 1 (NPC1) protein as the ebolavirus receptor and found that the inhibitor disrupts binding of cathepsin cleaved ebolavirus GP with NPC1.
The pathogenesis of many viruses is related to their envelope proteins. Dr. Misasi’s is currently focused on investigating the interactions between NPC1 and GP that lead to virus/cell membrane fusion and the mechanism by which his inhibitors block NPC1 binding to cleaved ebola GP. Dr. Misasi’s long term goal is to use chemical biology to identify host factors for hemorrhagic fever viruses and to investigate the interactions between these host factors and viral proteins in the hemorrhagic fever syndrome.
About John Misasi
John Misasi received his undergraduate degree in Biomedical Engineering from Boston University. He later attended SUNY-Upstate Medical University for Medical School. He completed his internship and residency in Pediatrics at New York University. After completing his residency training, he trained at Children's Hospital Boston in Infectious Diseases. He currently performs his research in the laboratory of Dr. James Cunningham of the Department of Virology at Harvard Medical School. He is a co-author of the “Marburg and Ebola viruses” chapter in the Clinical Decision Support-Infectious disease website.
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