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

Yates, Nicole L., Hua-Xin Liao, Youyi Fong, Allan deCamp, Nathan A. Vandergrift, William T. Williams, S Munir Alam, et al. “Vaccine-induced Env V1-V2 IgG3 correlates with lower HIV-1 infection risk and declines soon after vaccination.” Sci Transl Med 6, no. 228 (March 19, 2014): 228ra39. https://doi.org/10.1126/scitranslmed.3007730.

PMID
24648342
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Moody, M Anthony, Sampa Santra, Nathan A. Vandergrift, Laura L. Sutherland, Thaddeus C. Gurley, Mark S. Drinker, Ashley A. Allen, et al. “Toll-like receptor 7/8 (TLR7/8) and TLR9 agonists cooperate to enhance HIV-1 envelope antibody responses in rhesus macaques.” J Virol 88, no. 6 (March 2014): 3329–39. https://doi.org/10.1128/JVI.03309-13.

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24390332
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Zhang, Jinsong, S Munir Alam, Hilary Bouton-Verville, Yao Chen, Amanda Newman, Shelley Stewart, Frederick H. Jaeger, et al. “Modulation of nonneutralizing HIV-1 gp41 responses by an MHC-restricted TH epitope overlapping those of membrane proximal external region broadly neutralizing antibodies.” J Immunol 192, no. 4 (February 15, 2014): 1693–1706. https://doi.org/10.4049/jimmunol.1302511.

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24465011
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Lynch, Heather E., Shelley M. Stewart, Thomas B. Kepler, Gregory D. Sempowski, and S Munir Alam. “Surface plasmon resonance measurements of plasma antibody avidity during primary and secondary responses to anthrax protective antigen.” J Immunol Methods 404 (February 2014): 1–12. https://doi.org/10.1016/j.jim.2013.11.026.

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24316020
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Reardon, Patrick N., Harvey Sage, S Moses Dennison, Jeffrey W. Martin, Bruce R. Donald, S Munir Alam, Barton F. Haynes, and Leonard D. Spicer. “Structure of an HIV-1-neutralizing antibody target, the lipid-bound gp41 envelope membrane proximal region trimer.” Proc Natl Acad Sci U S A 111, no. 4 (January 28, 2014): 1391–96. https://doi.org/10.1073/pnas.1309842111.

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24474763
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Roederer, Mario, Brandon F. Keele, Stephen D. Schmidt, Rosemarie D. Mason, Hugh C. Welles, Will Fischer, Celia Labranche, et al. “Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV.” Nature 505, no. 7484 (January 23, 2014): 502–8. https://doi.org/10.1038/nature12893.

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24352234
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Lynch, H. E., S. M. Stewart, T. B. Kepler, G. D. Sempowski, and S. M. Alam. “Surface plasmon resonance measurements of plasma antibody avidity during primary and secondary responses to anthrax protective antigen.” Journal of Immunological Methods 404, no. 1 (2014): 1–12.

Scholars@Duke

Hwang, Kwan-Ki, Ashley M. Trama, Daniel M. Kozink, Xi Chen, Kevin Wiehe, Abby J. Cooper, Shi-Mao Xia, et al. “IGHV1-69 B cell chronic lymphocytic leukemia antibodies cross-react with HIV-1 and hepatitis C virus antigens as well as intestinal commensal bacteria.” Plos One 9, no. 3 (2014): e90725. https://doi.org/10.1371/journal.pone.0090725.

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24614505
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Kepler, Thomas B., Supriya Munshaw, Kevin Wiehe, Ruijun Zhang, Jae-Sung Yu, Christopher W. Woods, Thomas N. Denny, et al. “Reconstructing a B-Cell Clonal Lineage. II. Mutation, Selection, and Affinity Maturation.” Front Immunol 5 (2014): 170. https://doi.org/10.3389/fimmu.2014.00170.

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24795717
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Roederer, M., B. F. Keele, S. D. Schmidt, R. D. Mason, H. C. Welles, W. Fischer, C. Labranche, et al. “Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV.” Nature 505, no. 7484 (January 1, 2014): 502–8. https://doi.org/10.1038/nature12893.

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