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, Feng Gao, Thaddeus C. Gurley, Joshua D. Amos, Amit Kumar, Bhavna Hora, Dawn J. Marshall, et al. “Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses..” Cell Host Microbe 18, no. 3 (September 9, 2015): 354–62. https://doi.org/10.1016/j.chom.2015.08.006.

PMID
26355218
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Williams, Wilton B., Hua-Xin Liao, M Anthony Moody, Thomas B. Kepler, S Munir Alam, Feng Gao, Kevin Wiehe, et al. “HIV-1 VACCINES. Diversion of HIV-1 vaccine-induced immunity by gp41-microbiota cross-reactive antibodies..” Science 349, no. 6249 (August 14, 2015). https://doi.org/10.1126/science.aab1253.

PMID
26229114
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Wieczorek, Lindsay, Shelly J. Krebs, Vaniambadi Kalyanaraman, Stephen Whitney, Sodsai Tovanabutra, Carlos G. Moscoso, Eric Sanders-Buell, et al. “Comparable Antigenicity and Immunogenicity of Oligomeric Forms of a Novel, Acute HIV-1 Subtype C gp145 Envelope for Use in Preclinical and Clinical Vaccine Research..” J Virol 89, no. 15 (August 2015): 7478–93. https://doi.org/10.1128/JVI.00412-15.

PMID
25972551
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Santra, Sampa, Georgia D. Tomaras, Ranjit Warrier, Nathan I. Nicely, Hua-Xin Liao, Justin Pollara, Pinghuang Liu, et al. “Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques..” Plos Pathog 11, no. 8 (August 2015). https://doi.org/10.1371/journal.ppat.1005042.

PMID
26237403
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Permar, Sallie R., Youyi Fong, Nathan Vandergrift, Genevieve G. Fouda, Peter Gilbert, Robert Parks, Frederick H. Jaeger, et al. “Maternal HIV-1 envelope-specific antibody responses and reduced risk of perinatal transmission..” J Clin Invest 125, no. 7 (July 1, 2015): 2702–6. https://doi.org/10.1172/JCI81593.

PMID
26053661
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Nicely, Nathan I., Kevin Wiehe, Thomas B. Kepler, Frederick H. Jaeger, S Moses Dennison, Supachai Rerks-Ngarm, Sorachai Nitayaphan, et al. “Structural analysis of the unmutated ancestor of the HIV-1 envelope V2 region antibody CH58 isolated from an RV144 vaccine efficacy trial vaccinee..” Ebiomedicine 2, no. 7 (July 2015): 713–22. https://doi.org/10.1016/j.ebiom.2015.06.016.

PMID
26288844
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Hulot, Sandrine L., Bette Korber, Elena E. Giorgi, Nathan Vandergrift, Kevin O. Saunders, Harikrishnan Balachandran, Linh V. Mach, et al. “Comparison of Immunogenicity in Rhesus Macaques of Transmitted-Founder, HIV-1 Group M Consensus, and Trivalent Mosaic Envelope Vaccines Formulated as a DNA Prime, NYVAC, and Envelope Protein Boost..” J Virol 89, no. 12 (June 2015): 6462–80. https://doi.org/10.1128/JVI.00383-15.

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25855741
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Fusco, William G., Neelima R. Choudhary, Shelley M. Stewart, S Munir Alam, Gregory D. Sempowski, Christopher Elkins, and Isabelle Leduc. “Defining Potential Vaccine Targets of Haemophilus ducreyi Trimeric Autotransporter Adhesin DsrA..” Monoclon Antib Immunodiagn Immunother 34, no. 2 (April 2015): 73–82. https://doi.org/10.1089/mab.2014.0054.

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25897604
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Liu, Mengfei, Guang Yang, Kevin Wiehe, Nathan I. Nicely, Nathan A. Vandergrift, Wes Rountree, Mattia Bonsignori, et al. “Polyreactivity and autoreactivity among HIV-1 antibodies..” J Virol 89, no. 1 (January 2015): 784–98. https://doi.org/10.1128/JVI.02378-14.

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25355869
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Wiehe, Kevin, David Easterhoff, Kan Luo, Nathan I. Nicely, Todd Bradley, Frederick H. Jaeger, S Moses Dennison, et al. “Antibody light-chain-restricted recognition of the site of immune pressure in the RV144 HIV-1 vaccine trial is phylogenetically conserved..” Immunity 41, no. 6 (December 18, 2014): 909–18. https://doi.org/10.1016/j.immuni.2014.11.014.

PMID
25526306
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