S. Munir Alam, PhD

Professor in Medicine
Professor of Pathology
Member of the Duke Human Vaccine Institute
Campus mail 2 Genome Ct, MSRB II - Room 4004, Durham, NC 27710
Phone (919) 668-6372
Email address alam0004@mc.duke.edu

Research Interests. 

The Alam laboratory’s primary research is focused on understanding the biophysical properties of antigen-antibody binding and the molecular events of early B cell activation using the HIV-1 broadly neutralizing antibody (bnAb) lineage models. We are studying how HIV-1 Envelope proteins of varying affinities are sensed by B cells expressing HIV-1 bnAbs or their germline antigen receptors and initiate early signaling events for their activation. In the long-term these studies will facilitate design and pre-selection of immunogens for testing in animal models and accelerate HIV-1 vaccine development.
Current research include the following NIAID-funded projects   

Antigen recognition and activation of B cell antigen receptors with the specificity of HIV-1 broadly neutralizing antibodies. This project involves elucidating the early events on the B cell surface following antigen (Ag) engagement of the B cell antigen receptor (BCR) and to provide an assessment of the in vivo potential of an Ag to drive B cell activation. We are performing biophysical interactions analyses and using high-resolution microscopy to define the physico-chemical properties of BCR-Ag interactions that govern signaling and activation thresholds for BCR triggering and the BCR endocytic function in antigen internalization. The overall objective of these studies is to bridge the quantitative biophysical and membrane dynamics measurements of Ag-BCR interactions to ex-vivo and in-vivo B cell activation. This NIAID-funded research is a collaboration with co-investigators Professor Michael Reth (University of Freiburg, Germany) and Dr. Laurent Verkoczy (San Diego Biomedical Research Institute, CA).  

Immunogen Design for Induction of HIV gp41 Broadly Neutralizing Antibodies. This research project addresses the critical problem of vaccine induction of disfavored HIV-1 antibody lineages, like those that target the membrane proximal external region (MPER) of HIV Env gp41. This program combines structure and lineage-based vaccine development strategies to design immunogens that will induce bnAb lineages that are not polyreactive and therefore easier to induce. The overall objective of this program grant is to develop and test sequential immunogens that will initiate and induce HIV-1 bnAb lineages like the potent MPER bnAb DH511. Using a germline-targeting (GT) epitope scaffold design and a prime/boost strategy, we are testing induction of DH511-like bnAbs in knock-in (KI) mice models expressing the DH511 germline receptors. This P01 research program is in collaboration with Dr. William Schief (The Scripps Research Institute, CA), who leads the team that are designing germline targeting (GT)-scaffold prime and boost immunogens and Dr. Ming Tian at Harvard University who developed relevant knock-mice models for the study.

Education and Training

  • Ph.D., University of Glasgow (Scotland), 1992

Publications

Pegu, Poonam, Monica Vaccari, Shari Gordon, Brandon F. Keele, Melvin Doster, Yongjun Guan, Guido Ferrari, et al. “Antibodies with high avidity to the gp120 envelope protein in protection from simian immunodeficiency virus SIV(mac251) acquisition in an immunization regimen that mimics the RV-144 Thai trial..” J Virol 87, no. 3 (February 2013): 1708–19. https://doi.org/10.1128/JVI.02544-12.

PMID
23175374
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Liao, Hua-Xin, Mattia Bonsignori, S Munir Alam, Jason S. McLellan, Georgia D. Tomaras, M Anthony Moody, Daniel M. Kozink, et al. “Vaccine induction of antibodies against a structurally heterogeneous site of immune pressure within HIV-1 envelope protein variable regions 1 and 2..” Immunity 38, no. 1 (January 24, 2013): 176–86. https://doi.org/10.1016/j.immuni.2012.11.011.

PMID
23313589
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Fouda, Genevieve G., Tatenda Mahlokozera, Jesus F. Salazar-Gonzalez, Maria G. Salazar, Gerald Learn, Surender B. Kumar, S Moses Dennison, et al. “Postnatally-transmitted HIV-1 Envelope variants have similar neutralization-sensitivity and function to that of nontransmitted breast milk variants..” Retrovirology 10 (January 10, 2013). https://doi.org/10.1186/1742-4690-10-3.

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23305422
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Huang, Jinghe, Gilad Ofek, Leo Laub, Mark K. Louder, Nicole A. Doria-Rose, Nancy S. Longo, Hiromi Imamichi, et al. “Broad and potent neutralization of HIV-1 by a gp41-specific human antibody..” Nature 491, no. 7424 (November 15, 2012): 406–12. https://doi.org/10.1038/nature11544.

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23151583
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Bonsignori, Mattia, S Munir Alam, Hua-Xin Liao, Laurent Verkoczy, Georgia D. Tomaras, Barton F. Haynes, and M Anthony Moody. “HIV-1 antibodies from infection and vaccination: insights for guiding vaccine design..” Trends Microbiol 20, no. 11 (November 2012): 532–39. https://doi.org/10.1016/j.tim.2012.08.011.

PMID
22981828
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Petrovas, Constantinos, Takuya Yamamoto, Michael Y. Gerner, Kristin L. Boswell, Kaska Wloka, Emily C. Smith, David R. Ambrozak, et al. “CD4 T follicular helper cell dynamics during SIV infection..” J Clin Invest 122, no. 9 (September 2012): 3281–94. https://doi.org/10.1172/JCI63039.

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22922258
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Moody, M Anthony, Nicole L. Yates, Joshua D. Amos, Mark S. Drinker, Joshua A. Eudailey, Thaddeus C. Gurley, Dawn J. Marshall, et al. “HIV-1 gp120 vaccine induces affinity maturation in both new and persistent antibody clonal lineages..” J Virol 86, no. 14 (July 2012): 7496–7507. https://doi.org/10.1128/JVI.00426-12.

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22553329
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Haynes, Barton F., Peter B. Gilbert, M Juliana McElrath, Susan Zolla-Pazner, Georgia D. Tomaras, S Munir Alam, David T. Evans, et al. “Immune-correlates analysis of an HIV-1 vaccine efficacy trial..” N Engl J Med 366, no. 14 (April 5, 2012): 1275–86. https://doi.org/10.1056/NEJMoa1113425.

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22475592
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Hardy, Gregory J., Yee Lam, Shelley M. Stewart, Kara Anasti, S Munir Alam, and Stefan Zauscher. “Screening the interactions between HIV-1 neutralizing antibodies and model lipid surfaces..” J Immunol Methods 376, no. 1–2 (February 28, 2012): 13–19. https://doi.org/10.1016/j.jim.2011.10.005.

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22033342
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Friedman, James, S Munir Alam, Xiaoying Shen, Shi-Mao Xia, Shelley Stewart, Kara Anasti, Justin Pollara, et al. “Isolation of HIV-1-neutralizing mucosal monoclonal antibodies from human colostrum..” Plos One 7, no. 5 (2012). https://doi.org/10.1371/journal.pone.0037648.

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22624058
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