- Staff Scientist, NIDDK, NIH, 2007-present
- Research Fellow, NIDDK, NIH, 2004-2006
- Research Associate, Loyola University Medical Center, 2002-2004
- Visiting Fellow, NIDDK, NIH, 2000-2002
- Ph.D., Shanghai Institute of Biochemistry, 1999
The purpose of my research is to understand how human immunodeficiency virus (HIV) inserts its genetic material into human DNA, the mechanism of HIV drug resistance against integrase inhibitors (INIs), and to improve treatment and prevention of AIDS.
HIV-1 integrase (IN) plays a key role in the viral life cycle, catalyzing the viral DNA insertion into the genome of the host cell. DNA integration is essential for HIV replication, therefore, IN is an important therapeutic target in the fight against HIV/AIDS. Integrase inhibitors (INIs) are a class of antiretroviral drug designed to block the step of DNA integration.
Our current research is focused on biochemical and structural study of HIV-1 integration, especially on the indispensable intermediates, a series of stable nucleoprotein complexes of integrase, viral DNA ends, and target DNA along the integration pathway.
High-resolution structures of HIV-1 nucleoprotein complexes with and without integrase inhibitors allow us to understand the detailed mechanism of IN catalysis and provide insights of how the INIs block the enzymatic process at a molecular and atomic level.
Applying our Research
Approximately two decades of basic research on integrase has led several anti-HIV drugs targeting integrase onto the market. The biochemical details of the integration pathway and integrase function within the context of a nucleoprotein complex will facilitate the development of new classes of antiretroviral compounds.
Need for Further Study
Integrase inhibitors have demonstrated superior efficacy and excellent tolerability in clinical trials, however, the emergence of drug-resistant virus can result in virologic failure. The continued study of high-resolution structures of mutant IN nucleoprotein complex bound to INIs should improve our understanding the resistant mechanism and help guide the development of better antiretroviral therapeutics.
- A Peptide Derived from Lens Epithelium-Derived Growth Factor Stimulates HIV-1 DNA Integration and Facilitates Intasome Structural Studies.
- Li M, Chen X, Wang H, Jurado KA, Engelman AN, Craigie R.
- J Mol Biol (2020 Mar 27) 432:2055-2066. Abstract/Full Text
- Structural basis for strand-transfer inhibitor binding to HIV intasomes.
- Passos DO, Li M, Jóźwik IK, Zhao XZ, Santos-Martins D, Yang R, Smith SJ, Jeon Y, Forli S, Hughes SH, Burke TR Jr, Craigie R, Lyumkis D.
- Science (2020 Feb 14) 367:810-814. Abstract/Full Text
Research in Plain Language
I study how the virus that causes AIDS is able to invade a human cell and insert its genetic code into the host’s genome.