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

Li, Hui, Shuyi Wang, Rui Kong, Wenge Ding, Fang-Hua Lee, Zahra Parker, Eunlim Kim, et al. “Envelope residue 375 substitutions in simian-human immunodeficiency viruses enhance CD4 binding and replication in rhesus macaques..” Proc Natl Acad Sci U S A 113, no. 24 (June 14, 2016): E3413–22. https://doi.org/10.1073/pnas.1606636113.

PMID
27247400
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Bushey, Ryan T., M Anthony Moody, Nathan L. Nicely, Barton F. Haynes, S Munir Alam, Stephen T. Keir, Rex C. Bentley, et al. “A Therapeutic Antibody for Cancer, Derived from Single Human B Cells..” Cell Rep 15, no. 7 (May 17, 2016): 1505–13. https://doi.org/10.1016/j.celrep.2016.04.038.

PMID
27160908
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Zhang, Ruijun, Laurent Verkoczy, Kevin Wiehe, S. Munir Alam, Nathan I. Nicely, Sampa Santra, Todd Bradley, et al. “Initiation of immune tolerance-controlled HIV gp41 neutralizing B cell lineages..” Sci Transl Med 8, no. 336 (April 27, 2016). https://doi.org/10.1126/scitranslmed.aaf0618.

PMID
27122615
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Bonsignori, Mattia, Tongqing Zhou, Zizhang Sheng, Lei Chen, Feng Gao, M Gordon Joyce, Gabriel Ozorowski, et al. “Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody..” Cell 165, no. 2 (April 7, 2016): 449–63. https://doi.org/10.1016/j.cell.2016.02.022.

PMID
26949186
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Jeffries, T. L., C. R. Sacha, J. Pollara, J. Himes, F. H. Jaeger, S. M. Dennison, E. McGuire, et al. “The function and affinity maturation of HIV-1 gp120-specific monoclonal antibodies derived from colostral B cells..” Mucosal Immunol 9, no. 2 (March 2016): 414–27. https://doi.org/10.1038/mi.2015.70.

PMID
26242599
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Wang, Yuge, Pratibha Kapoor, Robert Parks, Aaron Silva-Sanchez, S Munir Alam, Laurent Verkoczy, Hua-Xin Liao, et al. “HIV-1 gp140 epitope recognition is influenced by immunoglobulin DH gene segment sequence..” Immunogenetics 68, no. 2 (February 2016): 145–55. https://doi.org/10.1007/s00251-015-0890-x.

PMID
26687685
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Bradley, Todd, Daniela Fera, Jinal Bhiman, Leila Eslamizar, Xiaozhi Lu, Kara Anasti, Ruijung Zhang, et al. “Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site..” Cell Rep 14, no. 1 (January 5, 2016): 43–54. https://doi.org/10.1016/j.celrep.2015.12.017.

PMID
26725118
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Mansour, Robin G., Lisa Stamper, Frederick Jaeger, Erin McGuire, Genevieve Fouda, Joshua Amos, Kimberly Barbas, et al. “The Presence and Anti-HIV-1 Function of Tenascin C in Breast Milk and Genital Fluids..” Plos One 11, no. 5 (2016). https://doi.org/10.1371/journal.pone.0155261.

PMID
27182834
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Soto, Cinque, Gilad Ofek, M Gordon Joyce, Baoshan Zhang, Krisha McKee, Nancy S. Longo, Yongping Yang, et al. “Developmental Pathway of the MPER-Directed HIV-1-Neutralizing Antibody 10E8..” Plos One 11, no. 6 (2016). https://doi.org/10.1371/journal.pone.0157409.

PMID
27299673
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Hraber, Peter, Bette Korber, Kshitij Wagh, Elena E. Giorgi, Tanmoy Bhattacharya, S. Gnanakaran, Alan S. Lapedes, et al. “Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants..” Viruses 7, no. 10 (October 21, 2015): 5443–75. https://doi.org/10.3390/v7102881.

PMID
26506369
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