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

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). https://doi.org/10.1371/journal.ppat.1008026.

PMID
31527908
Full Text

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). https://doi.org/10.1038/s41467-019-10899-2.

PMID
31263112
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Spearman, Paul, Georgia D. Tomaras, David C. Montefiori, Ying Huang, Marnie L. Elizaga, Guido Ferrari, S Munir Alam, et al. “Rapid Boosting of HIV-1 Neutralizing Antibody Responses in Humans Following a Prolonged Immunologic Rest Period..” J Infect Dis 219, no. 11 (May 5, 2019): 1755–65. https://doi.org/10.1093/infdis/jiz008.

PMID
30615119
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Krebs, Shelly J., Young D. Kwon, Chaim A. Schramm, William H. Law, Gina Donofrio, Kenneth H. Zhou, Syna Gift, et al. “Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual..” Immunity 50, no. 3 (March 19, 2019): 677-691.e13. https://doi.org/10.1016/j.immuni.2019.02.008.

PMID
30876875
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Dennis, Maria, Joshua Eudailey, Justin Pollara, Arthur S. McMillan, Kenneth D. Cronin, Pooja T. Saha, Alan D. Curtis, et al. “Coadministration of CH31 Broadly Neutralizing Antibody Does Not Affect Development of Vaccine-Induced Anti-HIV-1 Envelope Antibody Responses in Infant Rhesus Macaques..” J Virol 93, no. 5 (March 1, 2019). https://doi.org/10.1128/JVI.01783-18.

PMID
30541851
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Bonsignori, Mattia, Eric Scott, Kevin Wiehe, David Easterhoff, S Munir Alam, Kwan-Ki Hwang, Melissa Cooper, et al. “Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier..” Immunity 49, no. 6 (December 18, 2018): 1162-1174.e8. https://doi.org/10.1016/j.immuni.2018.10.015.

PMID
30552024
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Phillips, Bonnie, Koen K. A. Van Rompay, Jennifer Rodriguez-Nieves, Clarisse Lorin, Marguerite Koutsoukos, Mark Tomai, Christopher B. Fox, et al. “Adjuvant-Dependent Enhancement of HIV Env-Specific Antibody Responses in Infant Rhesus Macaques..” J Virol 92, no. 20 (October 15, 2018). https://doi.org/10.1128/JVI.01051-18.

PMID
30089691
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Dennison, S Moses, Matthew Reichartz, Kelly E. Seaton, Sheetij Dutta, Ulrike Wille-Reece, Adrian V. S. Hill, Katie J. Ewer, et al. “Qualified Biolayer Interferometry Avidity Measurements Distinguish the Heterogeneity of Antibody Interactions with Plasmodium falciparum Circumsporozoite Protein Antigens..” J Immunol 201, no. 4 (August 15, 2018): 1315–26. https://doi.org/10.4049/jimmunol.1800323.

PMID
30006374
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Wiehe, Kevin, Todd Bradley, R Ryan Meyerhoff, Connor Hart, Wilton B. Williams, David Easterhoff, William J. Faison, et al. “Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development..” Cell Host Microbe 23, no. 6 (June 13, 2018): 759-765.e6. https://doi.org/10.1016/j.chom.2018.04.018.

PMID
29861171
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Yates, Nicole L., Allan C. deCamp, Bette T. Korber, Hua-Xin Liao, Carmela Irene, Abraham Pinter, James Peacock, et al. “HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees..” J Virol 92, no. 8 (April 15, 2018). https://doi.org/10.1128/JVI.01843-17.

PMID
29386288
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