Jeffrey I. Cohen, M.D.
Chief, Medical Virology Section
Senior Investigator
Dr. Cohen received his M.D. from Johns Hopkins University and was an intern and resident in medicine at Duke University. Following a medical staff fellowship at the NIH, he was a clinical fellow in infectious diseases at the Brigham and Women’s Hospital and an instructor in medicine at Harvard University. He returned to NIH where he is chief of the Medical Virology Section in the Laboratory of Clinical Infectious Diseases.
Description of Research Program
We study the molecular genetics, pathogenesis, and clinical aspects of human herpesviruses, especially Epstein-Barr virus (EBV), varicella-zoster virus (VZV), and herpes simplex virus (HSV). The laboratory identifies genes important for virus infection and establishment of latency, searches for novel compounds for treatment of herpesvirus infections, and develops improved or new candidate vaccines for herpesvirus infections. We have produced a number of VZV, HSV, and EBV mutants and have analyzed the role of individual viral genes during infection both in vitro and in animal models. Studies focus on viral proteins important for latency, cell tropism, and interaction with cellular proteins.
The laboratory also collaborates with the Clinical Studies Unit to study autoimmune lymphoproliferative syndrome (ALPS), in which patients have defective apoptosis usually due to mutations in Fas.
We have identified a novel receptor for entry of VZV into cells and developed inhibitors that block infection of VZV into cells. We have constructed VZV mutants that replicate well in cell culture, but are impaired for latency in animals and may serve as safer candidate vaccines. We have found two compounds, simvastatin and bortezomib, that induce apoptosis of EBV-infected cells and inhibit development of EBV lymphomas in immunocompromised mice.
Clinical projects complement the laboratory studies. These include studies of patients with severe EBV disease to define genetic mutations or polymorphisms associated with the disease, studies of patients with HSV to characterize latent viral DNA in the nervous system, attempts to identify novel viruses in patients with unexplained syndromes, and analyses of immune responses after vaccination of volunteers with vaccinia.
Memberships
- American Association of Physicians
- American Society for Clinical Investigation
- Infectious Diseases Society of America
- Former chairman of Virology Interest Group
Editorial Boards
- Journal of Virology
- Virology
- Journal of Infectious Diseases
- Antiviral Therapy
Research Group Members
Qingxue Li, Kenning Wang, Sara Calattini, Juan Lacayo, Junichi Kawada, Yo Hoshino, Junji Sashihara, Janet Dale, Lesley Pesnicak, Kennichi Dowdell, Tammy Krogmann, Mir Ali
Selected Publications
(View list in PubMed.)
Zou P, Kawada J, Pesnicak L, Cohen JI. Bortezomib induces apoptosis of Epstein-Barr virus (EBV)-transformed B cells and prolongs survival of mice inoculated with EBV-transformed B cells. J Virol 2007; 81:10029-10036.
Wang K, Mahalingam G, Hoover SE, Mont EK, Holland SM, Cohen JI, Straus SE. Diverse HSV-1 thymidine kinase mutants in individual human neurons and ganglia. J Virol 2007;81:6817-26.
Cohen JI, Straus SE, Arvin AM. Varicella-zoster virus: Replication, pathogenesis, and management. In: Knipe DM, Howley PM, et al. Fields Virology. Philadelphia, Lipincott- Williams & Wilkins, 2007, pages 2773-2818.
Li Q, Ali, MA, Cohen JI. Insulin degrading enzyme is a cellular receptor for varicella-zoster virus infection and for cell-to-cell spread of virus. Cell 2006; 127:305-316.
Katano H, Ali MA, Patera AC, Catalfamo M, Jaffe ES, Kimura H, Dale JK, Straus, SE, Cohen JI. Chronic active Epstein-Barr virus infection associated with mutations in perforin that impair its maturation. Blood 2004;103:1244-1252.
Katano H, Pesnicak L, Cohen JI. Simvastatin induces apoptosis of Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines and delays development of EBV-lymphomas. Proc Natl Acad Sci USA. 2004;101: 4960-4965.
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