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

Easterhoff, David, M Anthony Moody, Daniela Fera, Hao Cheng, Margaret Ackerman, Kevin Wiehe, Kevin O. Saunders, et al. “Boosting of HIV envelope CD4 binding site antibodies with long variable heavy third complementarity determining region in the randomized double blind RV305 HIV-1 vaccine trial..” Plos Pathog 13, no. 2 (February 2017). https://doi.org/10.1371/journal.ppat.1006182.

PMID
28235027
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Bonsignori, Mattia, Hua-Xin Liao, Feng Gao, Wilton B. Williams, S Munir Alam, David C. Montefiori, and Barton F. Haynes. “Antibody-virus co-evolution in HIV infection: paths for HIV vaccine development..” Immunol Rev 275, no. 1 (January 2017): 145–60. https://doi.org/10.1111/imr.12509.

PMID
28133802
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Bradley, Todd, Guang Yang, Olga Ilkayeva, T Matt Holl, Ruijun Zhang, Jinsong Zhang, Sampa Santra, et al. “HIV-1 Envelope Mimicry of Host Enzyme Kynureninase Does Not Disrupt Tryptophan Metabolism..” J Immunol 197, no. 12 (December 15, 2016): 4663–73. https://doi.org/10.4049/jimmunol.1601484.

PMID
27849170
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Luo, Kan, Hua-Xin Liao, Ruijun Zhang, David Easterhoff, Kevin Wiehe, Thaddeus C. Gurley, Lawrence C. Armand, et al. “Tissue memory B cell repertoire analysis after ALVAC/AIDSVAX B/E gp120 immunization of rhesus macaques..” Jci Insight 1, no. 20 (December 8, 2016). https://doi.org/10.1172/jci.insight.88522.

PMID
27942585
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Huang, Jinghe, Byong H. Kang, Elise Ishida, Tongqing Zhou, Trevor Griesman, Zizhang Sheng, Fan Wu, et al. “Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth..” Immunity 45, no. 5 (November 15, 2016): 1108–21. https://doi.org/10.1016/j.immuni.2016.10.027.

PMID
27851912
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Bradley, Todd, Ashley Trama, Nancy Tumba, Elin Gray, Xiaozhi Lu, Navid Madani, Fatemeh Jahanbakhsh, et al. “Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity..” Ebiomedicine 12 (October 2016): 196–207. https://doi.org/10.1016/j.ebiom.2016.08.045.

PMID
27612593
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Kahsai, Alem W., James W. Wisler, Jungmin Lee, Seungkirl Ahn, Thomas J. Cahill Iii, S Moses Dennison, Dean P. Staus, et al. “Conformationally selective RNA aptamers allosterically modulate the β2-adrenoceptor..” Nat Chem Biol 12, no. 9 (September 2016): 709–16. https://doi.org/10.1038/nchembio.2126.

PMID
27398998
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Zhang, Ruijun, S Munir Alam, Jae-Sung Yu, Richard Scearce, Bradley Lockwood, Kwan-Ki Hwang, Robert Parks, et al. “Novel Monoclonal Antibodies for Studies of Human and Rhesus Macaque Secretory Component and Human J-Chain..” Monoclonal Antibodies in Immunodiagnosis and Immunotherapy 35, no. 4 (August 2016): 217–26. https://doi.org/10.1089/mab.2016.0014.

PMID
27386924
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Tay, Matthew Zirui, Pinghuang Liu, LaTonya D. Williams, Michael D. McRaven, Sheetal Sawant, Thaddeus C. Gurley, Thomas T. Xu, et al. “Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses..” Plos Pathog 12, no. 8 (August 2016). https://doi.org/10.1371/journal.ppat.1005817.

PMID
27579713
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Kwon, Young D., Ivelin S. Georgiev, Gilad Ofek, Baoshan Zhang, Mangaiarkarasi Asokan, Robert T. Bailer, Amy Bao, et al. “Optimization of the Solubility of HIV-1-Neutralizing Antibody 10E8 through Somatic Variation and Structure-Based Design..” J Virol 90, no. 13 (July 1, 2016): 5899–5914. https://doi.org/10.1128/JVI.03246-15.

PMID
27053554
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