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 (United Kingdom), 1992

Publications

Alam, S Munir, Kenneth Cronin, Robert Parks, Kara Anasti, Haitao Ding, Eden P. Go, Heather Desaire, et al. “Antigenicity and Immunogenicity of HIV-1 Envelope Trimers Complexed to a Small-Molecule Viral Entry Inhibitor.” J Virol 94, no. 21 (October 14, 2020). https://doi.org/10.1128/JVI.00958-20.

PMID
32817216
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Kasturi, Sudhir Pai, Mohammed Ata Ur Rasheed, Colin Havenar-Daughton, Mathew Pham, Traci Legere, Zarpheen Jinnah Sher, Yevgeny Kovalenkov, et al. “3M-052, a synthetic TLR-7/8 agonist, induces durable HIV-1 envelope-specific plasma cells and humoral immunity in nonhuman primates.” Sci Immunol 5, no. 48 (June 19, 2020). https://doi.org/10.1126/sciimmunol.abb1025.

PMID
32561559
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Curtis, Alan D., Maria Dennis, Joshua Eudailey, Korey L. Walter, Kenneth Cronin, S Munir Alam, Neelima Choudhary, et al. “HIV Env-Specific IgG Antibodies Induced by Vaccination of Neonatal Rhesus Macaques Persist and Can Be Augmented by a Late Booster Immunization in Infancy.” Msphere 5, no. 2 (March 25, 2020). https://doi.org/10.1128/mSphere.00162-20.

PMID
32213623
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Easterhoff, David, Justin Pollara, Kan Luo, William D. Tolbert, Brianna Young, Dieter Mielke, Shalini Jha, et al. “Boosting with AIDSVAX B/E Enhances Env Constant Region 1 and 2 Antibody-Dependent Cellular Cytotoxicity Breadth and Potency.” J Virol 94, no. 4 (January 31, 2020). https://doi.org/10.1128/JVI.01120-19.

PMID
31776278
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Saunders, Kevin O., Kevin Wiehe, Ming Tian, Priyamvada Acharya, Todd Bradley, S Munir Alam, Eden P. Go, et al. “Targeted selection of HIV-specific antibody mutations by engineering B cell maturation.” Science 366, no. 6470 (December 6, 2019). https://doi.org/10.1126/science.aay7199.

PMID
31806786
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LaBranche, Celia C., Rory Henderson, Allen Hsu, Shay Behrens, Xuejun Chen, Tongqing Zhou, Kevin Wiehe, et al. “Correction: Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies.” Plos Pathog 15, no. 12 (December 2019): e1008200. https://doi.org/10.1371/journal.ppat.1008200.

PMID
31790514
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Wu, Nelson R., Nathan I. Nicely, Esther M. Lee, Rachel K. Reed, Brian E. Watts, Fangping Cai, William E. Walkowicz, et al. “Cooperation between somatic mutation and germline-encoded residues enables antibody recognition of HIV-1 envelope glycans.” Plos Pathog 15, no. 12 (December 2019): e1008165. https://doi.org/10.1371/journal.ppat.1008165.

PMID
31841553
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LaBranche, Celia C., Rory Henderson, Allen Hsu, Shay Behrens, Xuejun Chen, Tongqing Zhou, Kevin Wiehe, et al. “Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies.” Plos Pathog 15, no. 9 (September 2019): e1008026. https://doi.org/10.1371/journal.ppat.1008026.

PMID
31527908
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Han, Qifeng, Julia A. Jones, Nathan I. Nicely, Rachel K. Reed, Xiaoying Shen, Katayoun Mansouri, Mark Louder, et al. “Difficult-to-neutralize global HIV-1 isolates are neutralized by antibodies targeting open envelope conformations.” Nat Commun 10, no. 1 (July 1, 2019): 2898. https://doi.org/10.1038/s41467-019-10899-2.

PMID
31263112
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Mangan, Riley J., Lisa Stamper, Tomoo Ohashi, Joshua A. Eudailey, Eden P. Go, Frederick H. Jaeger, Hannah L. Itell, et al. “Determinants of Tenascin-C and HIV-1 envelope binding and neutralization.” Mucosal Immunol 12, no. 4 (July 2019): 1004–12. https://doi.org/10.1038/s41385-019-0164-2.

PMID
30976088
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