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

Flynn, Barbara J., Kathrin Kastenmüller, Ulrike Wille-Reece, Georgia D. Tomaras, Munir Alam, Ross W. Lindsay, Andres M. Salazar, et al. “Immunization with HIV Gag targeted to dendritic cells followed by recombinant New York vaccinia virus induces robust T-cell immunity in nonhuman primates..” Proc Natl Acad Sci U S A 108, no. 17 (April 26, 2011): 7131–36. https://doi.org/10.1073/pnas.1103869108.

PMID
21467219
Full Text

Kasturi, Sudhir Pai, Ioanna Skountzou, Randy A. Albrecht, Dimitrios Koutsonanos, Tang Hua, Helder I. Nakaya, Rajesh Ravindran, et al. “Programming the magnitude and persistence of antibody responses with innate immunity..” Nature 470, no. 7335 (February 24, 2011): 543–47. https://doi.org/10.1038/nature09737.

PMID
21350488
Full Text

Dennison, S Moses, Kara Anasti, Richard M. Scearce, Laura Sutherland, Robert Parks, Shi-Mao Xia, Hua-Xin Liao, et al. “Nonneutralizing HIV-1 gp41 envelope cluster II human monoclonal antibodies show polyreactivity for binding to phospholipids and protein autoantigens..” J Virol 85, no. 3 (February 2011): 1340–47. https://doi.org/10.1128/JVI.01680-10.

PMID
21106741
Full Text

Moody, M Anthony, Ruijun Zhang, Emmanuel B. Walter, Christopher W. Woods, Geoffrey S. Ginsburg, Micah T. McClain, Thomas N. Denny, et al. “H3N2 influenza infection elicits more cross-reactive and less clonally expanded anti-hemagglutinin antibodies than influenza vaccination..” Plos One 6, no. 10 (2011). https://doi.org/10.1371/journal.pone.0025797.

PMID
22039424
Full Text

Dennison, S Moses, Laura L. Sutherland, Frederick H. Jaeger, Kara M. Anasti, Robert Parks, Shelley Stewart, Cindy Bowman, et al. “Induction of antibodies in rhesus macaques that recognize a fusion-intermediate conformation of HIV-1 gp41..” Plos One 6, no. 11 (2011). https://doi.org/10.1371/journal.pone.0027824.

PMID
22140469
Full Text

Morris, Lynn, Xi Chen, Munir Alam, Georgia Tomaras, Ruijun Zhang, Dawn J. Marshall, Bing Chen, et al. “Isolation of a human anti-HIV gp41 membrane proximal region neutralizing antibody by antigen-specific single B cell sorting..” Plos One 6, no. 9 (2011). https://doi.org/10.1371/journal.pone.0023532.

PMID
21980336
Full Text

Nicely, Nathan I., S Moses Dennison, Leonard Spicer, Richard M. Scearce, Garnett Kelsoe, Yoshihiro Ueda, Haiyan Chen, Hua-Xin Liao, S Munir Alam, and Barton F. Haynes. “Crystal structure of a non-neutralizing antibody to the HIV-1 gp41 membrane-proximal external region..” Nat Struct Mol Biol 17, no. 12 (December 2010): 1492–94. https://doi.org/10.1038/nsmb.1944.

PMID
21076400
Full Text

Saaem, I., K. S. Ma, S. M. Alam, and J. Tian. “Fabrication of plastic biochips.” Journal of Vacuum Science and Technology A: Vacuum, Surfaces and Films 28, no. 4 (July 1, 2010): 963–68. https://doi.org/10.1116/1.3432480.

Full Text

Haynes, Barton F., Nathan I. Nicely, and S Munir Alam. “HIV-1 autoreactive antibodies: are they good or bad for HIV-1 prevention?.” Nat Struct Mol Biol 17, no. 5 (May 2010): 543–45. https://doi.org/10.1038/nsmb0510-543.

PMID
20442740
Full Text

Zhang, Mei-Yun, Andrew Rosa Borges, Roger G. Ptak, Yanping Wang, Antony S. Dimitrov, S Munir Alam, Lindsay Wieczorek, et al. “Potent and broad neutralizing activity of a single chain antibody fragment against cell-free and cell-associated HIV-1..” Mabs 2, no. 3 (May 2010): 266–74. https://doi.org/10.4161/mabs.2.3.11416.

PMID
20305395
Full Text

Pages