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Alan N. Engelman, PhD

Professor, Department of Medicine, Harvard Medical School

Professor of Medicine, Cancer Immunology and AIDS, Dana-Farber Cancer Institute

Contact Info

Alan Engelman
Dana-Farber Cancer Institute
450 Brookline Avenue
Boston, MA, 02215
Mailstop: CLSB 1010
Phone: 617-632-4361
Fax: 617-632-4338
alan_engelman@dfci.harvard.edu

Assistant

McLaughlin Yvette
Administrative Assistant
Cancer Immunology and AIDS
Dana-Farber Cancer Institute
44 Binney Street
Boston, MA, 02115
Mailstop: CLSB 1010
Phone: 617-632-4351
Fax: 617-632-4338
Yvette_McLaughlin@dfci.harvard.edu

DF/HCC Program Affiliation

Cancer Cell Biology

Research Abstract

Dr. Engelman focuses on the mechanism of human immunodeficiency virus type 1 (HIV-1) integration, an essential step in the viral lifecycle. Retroviruses encode their own integrase protein, and Dr. Engelman's research borrows form numerous disciplines including molecular virology and structural biology to understand mechanistic details of integrase function. Integrase active site inhibitors have been in the clinic since 2007, but until recently their mode of action was largely speculative. Novel X-ray crystal structures of the related spumavirus integrase with its DNA substrate yielded unprecedented details of the structural basis of retroviral DNA integration and moreover established how the inhibitors work. Lentiviruses like HIV-1 preferentially target active genes during integration, and Dr. Engelman’s research established that an interaction between integrase and the cellular chromatin binding protein lens epithelium-derived growth factor (LEDGF) plays a significant role in HIV integration targeting. Because X-ray crystal structures pinpointed the LEDGF binding face distal from the integrase active site, small molecule inhibitors of the LEDGF-integrase interaction should afford a novel way to block HIV-1 replication in cells.

Publications

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