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

Alam, S Munir, Hua-Xin Liao, S Moses Dennison, Frederick Jaeger, Robert Parks, Kara Anasti, Andrew Foulger, et al. “Differential reactivity of germ line allelic variants of a broadly neutralizing HIV-1 antibody to a gp41 fusion intermediate conformation..” J Virol 85, no. 22 (November 2011): 11725–31. https://doi.org/10.1128/JVI.05680-11.

PMID
21917975
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Tomaras, Georgia D., James M. Binley, Elin S. Gray, Emma T. Crooks, Keiko Osawa, Penny L. Moore, Nancy Tumba, et al. “Polyclonal B cell responses to conserved neutralization epitopes in a subset of HIV-1-infected individuals..” J Virol 85, no. 21 (November 2011): 11502–19. https://doi.org/10.1128/JVI.05363-11.

PMID
21849452
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Liu, Pinghuang, R Glenn Overman, Nicole L. Yates, S Munir Alam, Nathan Vandergrift, Yue Chen, Frederik Graw, et al. “Dynamic antibody specificities and virion concentrations in circulating immune complexes in acute to chronic HIV-1 infection..” J Virol 85, no. 21 (November 2011): 11196–207. https://doi.org/10.1128/JVI.05601-11.

PMID
21865397
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Liao, Hua-Xin, Xi Chen, Supriya Munshaw, Ruijun Zhang, Dawn J. Marshall, Nathan Vandergrift, John F. Whitesides, et al. “Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated..” J Exp Med 208, no. 11 (October 24, 2011): 2237–49. https://doi.org/10.1084/jem.20110363.

PMID
21987658
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Verkoczy, Laurent, Yao Chen, Hilary Bouton-Verville, Jinsong Zhang, Marilyn Diaz, Jennifer Hutchinson, Ying-Bin Ouyang, et al. “Rescue of HIV-1 broad neutralizing antibody-expressing B cells in 2F5 VH x VL knockin mice reveals multiple tolerance controls..” J Immunol 187, no. 7 (October 1, 2011): 3785–97. https://doi.org/10.4049/jimmunol.1101633.

PMID
21908739
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Bonsignori, M., X. Wu, M. A. Moody, H. Liao, K. Hwang, J. A. Crump, S. H. Capiga, et al. “Isolation of CD4-Binding Site and V2/V3 Conformational (Quaternary) Broadly Neutralizing Antibodies from the Same HIV-1 Infected African Subject.” In Aids Research and Human Retroviruses, 27:A120–A120. MARY ANN LIEBERT INC, 2011.

Scholars@Duke

Bonsignori, Mattia, Kwan-Ki Hwang, Xi Chen, Chun-Yen Tsao, Lynn Morris, Elin Gray, Dawn J. Marshall, et al. “Analysis of a clonal lineage of HIV-1 envelope V2/V3 conformational epitope-specific broadly neutralizing antibodies and their inferred unmutated common ancestors..” J Virol 85, no. 19 (October 2011): 9998–10009. https://doi.org/10.1128/JVI.05045-11.

PMID
21795340
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Cale, Evan M., Heidi S. Bazick, Tony A. Rianprakaisang, S Munir Alam, and Norman L. Letvin. “Mutations in a dominant Nef epitope of simian immunodeficiency virus diminish TCR:epitope peptide affinity but not epitope peptide:MHC class I binding..” J Immunol 187, no. 6 (September 15, 2011): 3300–3313. https://doi.org/10.4049/jimmunol.1101080.

PMID
21841125
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Ma, Ben-Jiang, S Munir Alam, Eden P. Go, Xiaozhi Lu, Heather Desaire, Georgia D. Tomaras, Cindy Bowman, et al. “Envelope deglycosylation enhances antigenicity of HIV-1 gp41 epitopes for both broad neutralizing antibodies and their unmutated ancestor antibodies..” Plos Pathog 7, no. 9 (September 2011). https://doi.org/10.1371/journal.ppat.1002200.

PMID
21909262
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Ferrari, Guido, Justin Pollara, Daniel Kozink, Tiara Harms, Mark Drinker, Stephanie Freel, M Anthony Moody, et al. “An HIV-1 gp120 envelope human monoclonal antibody that recognizes a C1 conformational epitope mediates potent antibody-dependent cellular cytotoxicity (ADCC) activity and defines a common ADCC epitope in human HIV-1 serum..” J Virol 85, no. 14 (July 2011): 7029–36. https://doi.org/10.1128/JVI.00171-11.

PMID
21543485
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