DF/HCC Program Affiliation

Cancer Cell Biology

Research Abstract

Dr. Engelman focuses on the mechanism of human immunodeficiency virus type 1 (HIV-1) integration in infected cells. Like all retroviruses, HIV-1 must integrate a DNA copy of its RNA genome into a cell chromosome in order to replicate. Retroviruses encode their own DNA recombination protein, called integrase, that accomplishes this task. Unlike reverse transcriptase and protease, the two other retroviral enzymes currently targeted by HAART therapy, there are no known cellular analogs of the integrase protein in human cells. Thus, it is hoped that the eventual development of anti-integrase drugs will not only increase the target repertoire of the currently available drugs, but will also yield compounds less toxic to AIDS patients than are the currently available inhibitors. Developing effective drugs against integrase requires detailed working knowldege of the integration process in infected cells.

Publications

• Hare S, Di Nunzio F, Labeja A, Wang J, Engelman A, Cherepanov P.Structural basis for functional tetramerization of lentiviral integrase.PLoS Pathog. 2009 Jul;5(7):e1000515.
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• Hare S, Shun MC, Gupta SS, Valkov E, Engelman A, Cherepanov P.A novel co-crystal structure affords the design of gain-of-function lentiviral integrase mutants in the presence of modified PSIP1/LEDGF/p75.PLoS Pathog. 2009 Jan;5(1):e1000259.
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• Shun MC,Botbol Y,Li X,Di Nunzio F,Daigle JE,Yan N,Lieberman J,Lavigne M,Engelman A.Identification and characterization of PWWP domain residues critical for LEDGF/p75 chromatin binding and human immunodeficiency virus type 1 infectivity.J Virol 2008 Dec;82
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• Shun MC, Raghavendra NK, Vandegraaff N, Daigle JE, Hughes S, Kellam P, Cherepanov P, Engelman A.LEDGF/p75 functions downstream from preintegration complex formation to effect gene-specific HIV-1 integration.Genes Dev 2007 Jul 15;21(14):1767-78.
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