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

Wills, Saintedym, Kwan-Ki Hwang, Pinghuang Liu, S Moses Dennison, Matthew Zirui Tay, Xiaoying Shen, Justin Pollara, et al. “HIV-1-Specific IgA Monoclonal Antibodies from an HIV-1 Vaccinee Mediate Galactosylceramide Blocking and Phagocytosis..” J Virol 92, no. 7 (April 1, 2018). https://doi.org/10.1128/JVI.01552-17.

PMID
29321320
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Saunders, Kevin O., Laurent K. Verkoczy, Chuancang Jiang, Jinsong Zhang, Robert Parks, Haiyan Chen, Max Housman, et al. “Vaccine Induction of Heterologous Tier 2 HIV-1 Neutralizing Antibodies in Animal Models..” Cell Rep 21, no. 13 (December 26, 2017): 3681–90. https://doi.org/10.1016/j.celrep.2017.12.028.

PMID
29281818
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Shen, Xiaoying, Rahul Basu, Sheetal Sawant, David Beaumont, Sue Fen Kwa, Celia LaBranche, Kelly E. Seaton, et al. “HIV-1 gp120 and Modified Vaccinia Virus Ankara (MVA) gp140 Boost Immunogens Increase Immunogenicity of a DNA/MVA HIV-1 Vaccine..” J Virol 91, no. 24 (December 15, 2017). https://doi.org/10.1128/JVI.01077-17.

PMID
29021394
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Williams, Wilton B., Jinsong Zhang, Chuancang Jiang, Nathan I. Nicely, Daniela Fera, Kan Luo, M Anthony Moody, et al. “Initiation of HIV neutralizing B cell lineages with sequential envelope immunizations..” Nat Commun 8, no. 1 (November 23, 2017). https://doi.org/10.1038/s41467-017-01336-3.

PMID
29170366
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Shen, Xiaoying, Willy M. Bogers, Nicole L. Yates, Guido Ferrari, Antu K. Dey, William T. Williams, Frederick H. Jaeger, et al. “Cross-Linking of a CD4-Mimetic Miniprotein with HIV-1 Env gp140 Alters Kinetics and Specificities of Antibody Responses against HIV-1 Env in Macaques..” J Virol 91, no. 19 (October 1, 2017). https://doi.org/10.1128/JVI.00401-17.

PMID
28490585
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Meyerhoff, R Ryan, Richard M. Scearce, Damon F. Ogburn, Brad Lockwood, Joy Pickeral, Masa Kuraoka, Kara Anasti, et al. “HIV-1 Consensus Envelope-Induced Broadly Binding Antibodies..” Aids Res Hum Retroviruses 33, no. 8 (August 2017): 859–68. https://doi.org/10.1089/AID.2016.0294.

PMID
28314374
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Alam, S Munir, Baptiste Aussedat, Yusuf Vohra, R Ryan Meyerhoff, Evan M. Cale, William E. Walkowicz, Nathan A. Radakovich, et al. “Mimicry of an HIV broadly neutralizing antibody epitope with a synthetic glycopeptide..” Sci Transl Med 9, no. 381 (March 15, 2017). https://doi.org/10.1126/scitranslmed.aai7521.

PMID
28298421
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Bonsignori, Mattia, Edward F. Kreider, Daniela Fera, R Ryan Meyerhoff, Todd Bradley, Kevin Wiehe, S Munir Alam, et al. “Staged induction of HIV-1 glycan-dependent broadly neutralizing antibodies..” Sci Transl Med 9, no. 381 (March 15, 2017). https://doi.org/10.1126/scitranslmed.aai7514.

PMID
28298420
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Saunders, Kevin O., Nathan I. Nicely, Kevin Wiehe, Mattia Bonsignori, R Ryan Meyerhoff, Robert Parks, William E. Walkowicz, et al. “Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates..” Cell Rep 18, no. 9 (February 28, 2017): 2175–88. https://doi.org/10.1016/j.celrep.2017.02.003.

PMID
28249163
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Wiehe, Kevin, Nathan I. Nicely, Bradley Lockwood, Masayuki Kuraoka, Kara Anasti, Sabrina Arora, Cindy M. Bowman, et al. “Immunodominance of Antibody Recognition of the HIV Envelope V2 Region in Ig-Humanized Mice..” J Immunol 198, no. 3 (February 1, 2017): 1047–55. https://doi.org/10.4049/jimmunol.1601640.

PMID
28011932
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