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

Huang, Jinghe, Byong H. Kang, Marie Pancera, Jeong Hyun Lee, Tommy Tong, Yu Feng, Hiromi Imamichi, et al. “Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface.” Nature 515, no. 7525 (November 6, 2014): 138–42. https://doi.org/10.1038/nature13601.

PMID
25186731
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Hardy, Gregory J., Gene C. Wong, Rahul Nayak, Kara Anasti, Michael Hirtz, Joseph G. Shapter, S Munir Alam, and Stefan Zauscher. “HIV-1 antibodies and vaccine antigen selectively interact with lipid domains.” Biochim Biophys Acta 1838, no. 10 (October 2014): 2662–69. https://doi.org/10.1016/j.bbamem.2014.07.007.

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25019685
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Kepler, Thomas B., Hua-Xin Liao, S Munir Alam, Rekha Bhaskarabhatla, Ruijun Zhang, Chandri Yandava, Shelley Stewart, et al. “Immunoglobulin gene insertions and deletions in the affinity maturation of HIV-1 broadly reactive neutralizing antibodies.” Cell Host Microbe 16, no. 3 (September 10, 2014): 304–13. https://doi.org/10.1016/j.chom.2014.08.006.

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25211073
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Trama, Ashley M., M Anthony Moody, S Munir Alam, Frederick H. Jaeger, Bradley Lockwood, Robert Parks, Krissey E. Lloyd, et al. “HIV-1 envelope gp41 antibodies can originate from terminal ileum B cells that share cross-reactivity with commensal bacteria.” Cell Host Microbe 16, no. 2 (August 13, 2014): 215–26. https://doi.org/10.1016/j.chom.2014.07.003.

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25121750
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Dennison, S Moses, Kara M. Anasti, Frederick H. Jaeger, Shelley M. Stewart, Justin Pollara, Pinghuang Liu, Erika L. Kunz, et al. “Vaccine-induced HIV-1 envelope gp120 constant region 1-specific antibodies expose a CD4-inducible epitope and block the interaction of HIV-1 gp140 with galactosylceramide.” J Virol 88, no. 16 (August 2014): 9406–17. https://doi.org/10.1128/JVI.01031-14.

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24920809
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Gao, Feng, Mattia Bonsignori, Hua-Xin Liao, Amit Kumar, Shi-Mao Xia, Xiaozhi Lu, Fangping Cai, et al. “Cooperation of B cell lineages in induction of HIV-1-broadly neutralizing antibodies.” Cell 158, no. 3 (July 31, 2014): 481–91. https://doi.org/10.1016/j.cell.2014.06.022.

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25065977
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Haynes, Barton F., M Anthony Moody, Munir Alam, Mattia Bonsignori, Laurent Verkoczy, Guido Ferrari, Feng Gao, Georgia D. Tomaras, Hua-Xin Liao, and Garnett Kelsoe. “Progress in HIV-1 vaccine development.” J Allergy Clin Immunol 134, no. 1 (July 2014): 3–10. https://doi.org/10.1016/j.jaci.2014.04.025.

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25117798
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Pollara, Justin, Mattia Bonsignori, M Anthony Moody, Pinghuang Liu, S Munir Alam, Kwan-Ki Hwang, Thaddeus C. Gurley, et al. “HIV-1 vaccine-induced C1 and V2 Env-specific antibodies synergize for increased antiviral activities.” J Virol 88, no. 14 (July 2014): 7715–26. https://doi.org/10.1128/JVI.00156-14.

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24807721
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Holl, T Matt, Guang Yang, Masayuki Kuraoka, Laurent Verkoczy, S Munir Alam, M Anthony Moody, Barton F. Haynes, and Garnett Kelsoe. “Enhanced antibody responses to an HIV-1 membrane-proximal external region antigen in mice reconstituted with cultured lymphocytes.” J Immunol 192, no. 7 (April 1, 2014): 3269–79. https://doi.org/10.4049/jimmunol.1302829.

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24591365
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Osuna, Christa E., Ana Maria Gonzalez, Hsun-Hsien Chang, Amy Shi Hung, Elizabeth Ehlinger, Kara Anasti, S Munir Alam, and Norman L. Letvin. “TCR affinity associated with functional differences between dominant and subdominant SIV epitope-specific CD8+ T cells in Mamu-A*01+ rhesus monkeys.” Plos Pathog 10, no. 4 (April 2014): e1004069. https://doi.org/10.1371/journal.ppat.1004069.

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24743648
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