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

Moody, M Anthony, Hua-Xin Liao, S Munir Alam, Richard M. Scearce, M Kelly Plonk, Daniel M. Kozink, Mark S. Drinker, et al. “Anti-phospholipid human monoclonal antibodies inhibit CCR5-tropic HIV-1 and induce beta-chemokines..” J Exp Med 207, no. 4 (April 12, 2010): 763–76. https://doi.org/10.1084/jem.20091281.

PMID
20368576
Full Text

Shen, Xiaoying, S Moses Dennison, Pinghuang Liu, Feng Gao, Frederick Jaeger, David C. Montefiori, Laurent Verkoczy, Barton F. Haynes, S Munir Alam, and Georgia D. Tomaras. “Prolonged exposure of the HIV-1 gp41 membrane proximal region with L669S substitution..” Proc Natl Acad Sci U S A 107, no. 13 (March 30, 2010): 5972–77. https://doi.org/10.1073/pnas.0912381107.

PMID
20231447
Full Text

Verkoczy, Laurent, Marilyn Diaz, T Matt Holl, Ying-Bin Ouyang, Hilary Bouton-Verville, S Munir Alam, Hua-Xin Liao, Garnett Kelsoe, and Barton F. Haynes. “Autoreactivity in an HIV-1 broadly reactive neutralizing antibody variable region heavy chain induces immunologic tolerance..” Proc Natl Acad Sci U S A 107, no. 1 (January 5, 2010): 181–86. https://doi.org/10.1073/pnas.0912914107.

PMID
20018688
Full Text

Alam, S Munir, Marco Morelli, S Moses Dennison, Hua-Xin Liao, Ruijun Zhang, Shi-Mao Xia, Sophia Rits-Volloch, et al. “Role of HIV membrane in neutralization by two broadly neutralizing antibodies..” Proc Natl Acad Sci U S A 106, no. 48 (December 1, 2009): 20234–39. https://doi.org/10.1073/pnas.0908713106.

PMID
19906992
Full Text

Gao, Feng, Richard M. Scearce, S Munir Alam, Bhavna Hora, Shimao Xia, Julie E. Hohm, Robert J. Parks, et al. “Cross-reactive monoclonal antibodies to multiple HIV-1 subtype and SIVcpz envelope glycoproteins..” Virology 394, no. 1 (November 10, 2009): 91–98. https://doi.org/10.1016/j.virol.2009.07.041.

PMID
19744690
Full Text

Holl, T. M., M. Kuraoka, D. Liao, L. Verkoczy, M. A. Moody, M. Alam, H. Liao, B. F. Haynes, and G. H. Kelsoe. “P04-44. Generation of antibody responses to HIV-1 membrane proximal external region (MPER) antigen.” Retrovirology 6, no. SUPPL. 3 (October 22, 2009). https://doi.org/10.1186/1742-4690-6-S3-P72.

Full Text

Desaire, H., B. F. Haynes, E. P. Go, H. Liao, L. L. Sutherland, Q. Chang, Y. Zhang, J. Irungu, and S. M. Alam. “P20-08. Glycosylation: An important factor in Env diversity.” Retrovirology 6, no. SUPPL. 3 (October 22, 2009). https://doi.org/10.1186/1742-4690-6-S3-P378.

Full Text

Verkoczy, L., M. Diaz, T. M. Holl, Y. Ouyang, H. Bouton-Verville, S. M. Alam, H. Liao, G. Kelsoe, and B. F. Haynes. “P04-26. Immunological tolerance prevents the expression of a broadly reactive neutralizing HIV-1 antibody.” Retrovirology 6, no. SUPPL. 3 (October 22, 2009). https://doi.org/10.1186/1742-4690-6-S3-P54.

Full Text

Shen, X., M. Dennison, F. Gao, D. C. Montefiori, L. Verkoczy, B. Haynes, M. Alam, and G. Tomaras. “OA021-04. HIV-1 gp41 envelope MPER mutation altered epitope conformation in lipid and increased sensitivity to 2F5 and 4E10 neutralizing antibodies.” In Retrovirology, Vol. 6, 2009. https://doi.org/10.1186/1742-4690-6-S3-O16.

Full Text

Verkoczy, Laurent, M Anthony Moody, T Matt Holl, Hilary Bouton-Verville, Richard M. Scearce, Jennifer Hutchinson, S Munir Alam, Garnett Kelsoe, and Barton F. Haynes. “Functional, non-clonal IgMa-restricted B cell receptor interactions with the HIV-1 envelope gp41 membrane proximal external region..” Plos One 4, no. 10 (October 6, 2009). https://doi.org/10.1371/journal.pone.0007215.

PMID
19806186
Full Text

Pages