Manish Sagar, M.D.
Associate Professor of Medicine and Microbiology
Evans Biomedical Research Building
650 Albany Street
Office: X647; 617-414-5239
B.S. Columbia University
M.D. Johns Hopkins University
Our laboratory is primarily interested in human immunodeficiency virus type 1 (HIV-1) pathogenesis. One are of focus is to understand the biological mechanisms for the selection observed during HIV-1 transmission. Even though chronically infected subjects harbor extensive variants during transmission, only a limited number of viruses are acquired by newly infected partners. Genotypic examination of viruses present in the newly infected subject compared to those circulating in the transmitting partner suggests that the observed genetic bottleneck during transmission is not due to random chance. Laboratory studies explore the hypothesis that during transmission there is selection of specific variants with properties that confer fitness for transmission.
Another focus in the lab is to decipher correlate of immune protection. Even though infants are exposed to infected breast milk, only a small proportion (around 30%) acquire HIV-1 from their infected mother in the absence of antiretroviral protection. We hypothesize that maternally acquired antibodies present in the infant prevent HIV-1 acquisition either through neutralization or antibody dependent cellular cytotoxicity against the variants circulating in the maternal breast milk. Defining the immune correlate of protection will have important implications for HIV-1 vaccine design.
- Sagar M, Laeyendecker O, Lee S, Gamiel J, Wawer MJ, Gray RH, Serwadda D, Sewankambo NK, Shepherd JC, Toma J, Huang W, Quinn TC. 2009. Selection of HIV variants with signature genotypic characteristics during heterosexual transmission. J Infec Dis. 199: 580-9. PMID: 19143562
- Etemad B, Fellows A, Kamat A, Kwambana B, Sagar M. 2009. HIV-1 V1-V5 envelope variants from the chronic phase of infection use CCR5 and fuse more efficiently than those from early after infection J Virol. 83(19):9694-708. PMID: 19625411
- Sagar M, Akiyama H, Etemad B, Ramirez N, Freitas I, Gummuluru S. 2012. Transmembrane Domain Membrane Proximal External Region but not Surface Unit Directed Broadly Neutralizing HIV-1 Antibodies can Restrict Dendritic Cell Mediated HIV-1 Trans Infection. J Infect Dis. 205(8):1248-57. PMID: 22396600
- Chatziandreou N, Belen Arauz A, Freitas I, Nyein PH, Fenton G, Mehta SH,. Kirk GD Sagar M. 2012. Sensitivity changes over the course of infection increases the likelihood of resistance against fusion but not CCR5 receptor blockers. AIDS Res Hum Retroviruses 28(12):1584-93. PMID: 22650962
- Redd AD, Collinson-Streng AN, Chatziandreou N, Mullis CE, Laeyendecker O, Martens C, Ricklefs S, Kiwanuka N, Nyein PH, Lutalo T, Kong X, Manucci J, Sewankambo N, Wawer MJ, Gray RH, Porcella SF, Fauci AS, Sagar M, Serwadda D, and Quinn TC. 2012. Previously transmitted HIV-1 viral strains are preferentially selected during subsequent sexual transmissions. J Infect Dis. 206(9):1433-42. PMID: 22997233
- Lin N, Becerril, C, Giguel F, Novitsky V, Moyo S, Makhema J, Essex M, Lockman S, Kuritzkes D, Sagar M. 2012. Env Sequence Determinants in CXCR4-using Human Immunodeficiency Virus Type-1 Subtype C. Virol. 433(2):296-307. PMID: 22954962
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