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

Liu, Pinghuang, Nicole L. Yates, Xiaoying Shen, Mattia Bonsignori, M Anthony Moody, Hua-Xin Liao, Youyi Fong, et al. “Infectious virion capture by HIV-1 gp120-specific IgG from RV144 vaccinees.” J Virol 87, no. 14 (July 2013): 7828–36. https://doi.org/10.1128/JVI.02737-12.

PMID
23658446
Full Text

Pancera, Marie, Syed Shahzad-Ul-Hussan, Nicole A. Doria-Rose, Jason S. McLellan, Robert T. Bailer, Kaifan Dai, Sandra Loesgen, et al. “Structural basis for diverse N-glycan recognition by HIV-1-neutralizing V1-V2-directed antibody PG16.” Nat Struct Mol Biol 20, no. 7 (July 2013): 804–13. https://doi.org/10.1038/nsmb.2600.

PMID
23708607
Full Text

Tomaras, Georgia D., Guido Ferrari, Xiaoying Shen, S Munir Alam, Hua-Xin Liao, Justin Pollara, Mattia Bonsignori, et al. “Vaccine-induced plasma IgA specific for the C1 region of the HIV-1 envelope blocks binding and effector function of IgG.” Proc Natl Acad Sci U S A 110, no. 22 (May 28, 2013): 9019–24. https://doi.org/10.1073/pnas.1301456110.

PMID
23661056
Full Text

Liao, Hua-Xin, Rebecca Lynch, Tongqing Zhou, Feng Gao, S Munir Alam, Scott D. Boyd, Andrew Z. Fire, et al. “Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus.” Nature 496, no. 7446 (April 25, 2013): 469–76. https://doi.org/10.1038/nature12053.

PMID
23552890
Full Text

Zhu, Jiang, Gilad Ofek, Yongping Yang, Baoshan Zhang, Mark K. Louder, Gabriel Lu, Krisha McKee, et al. “Mining the antibodyome for HIV-1-neutralizing antibodies with next-generation sequencing and phylogenetic pairing of heavy/light chains.” Proc Natl Acad Sci U S A 110, no. 16 (April 16, 2013): 6470–75. https://doi.org/10.1073/pnas.1219320110.

PMID
23536288
Full Text

Liao, Hua-Xin, Chun-Yen Tsao, S Munir Alam, Mark Muldoon, Nathan Vandergrift, Ben-Jiang Ma, Xiaozhi Lu, et al. “Antigenicity and immunogenicity of transmitted/founder, consensus, and chronic envelope glycoproteins of human immunodeficiency virus type 1.” J Virol 87, no. 8 (April 2013): 4185–4201. https://doi.org/10.1128/JVI.02297-12.

PMID
23365441
Full Text

Go, Eden P., Hua-Xin Liao, S Munir Alam, David Hua, Barton F. Haynes, and Heather Desaire. “Characterization of host-cell line specific glycosylation profiles of early transmitted/founder HIV-1 gp120 envelope proteins.” J Proteome Res 12, no. 3 (March 1, 2013): 1223–34. https://doi.org/10.1021/pr300870t.

PMID
23339644
Full Text

Yang, Guang, T Matt Holl, Yang Liu, Yi Li, Xiaozhi Lu, Nathan I. Nicely, Thomas B. Kepler, et al. “Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies.” J Exp Med 210, no. 2 (February 11, 2013): 241–56. https://doi.org/10.1084/jem.20121977.

PMID
23359068
Full Text

Alam, S Munir, Hua-Xin Liao, Georgia D. Tomaras, Mattia Bonsignori, Chun-Yen Tsao, Kwan-Ki Hwang, Haiyan Chen, et al. “Antigenicity and immunogenicity of RV144 vaccine AIDSVAX clade E envelope immunogen is enhanced by a gp120 N-terminal deletion.” J Virol 87, no. 3 (February 2013): 1554–68. https://doi.org/10.1128/JVI.00718-12.

PMID
23175357
Full Text

Pegu, Poonam, Monica Vaccari, Shari Gordon, Brandon F. Keele, Melvin Doster, Yongjun Guan, Guido Ferrari, et al. “Antibodies with high avidity to the gp120 envelope protein in protection from simian immunodeficiency virus SIV(mac251) acquisition in an immunization regimen that mimics the RV-144 Thai trial.” J Virol 87, no. 3 (February 2013): 1708–19. https://doi.org/10.1128/JVI.02544-12.

PMID
23175374
Full Text

Pages