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.
Biophysical analysis of coreceptor modulation of TCR-MHC interactions. One of our research interests is to study the molecular mechanisms of T cell recognition. We have particular interest in understanding the trimolecular interactions between membrane bound T cell receptor (TCR-CD3 complex) and its ligand, the peptide-MHC complex (pMHC), and co-receptor molecules. We are using different biophysical approaches which include surface plasmon resonance, isothermal titration calorimetry and atomic force spectroscopy to study the influence of co-stimulatory molecules on the kinetics and thermodynamics of TCR-pMHC binding. The goal is to use integrated molecular and biophysical approaches to study membrane TCR-MHC interactions and to understand how these interactions are modulated by co-receptors during T cell development and activation.
Energetics and kinetics of monoclonal antibody binding to soluble HIV Envelope proteins. An additional interest of our lab involves biophysical characterization of soluble, recombinant human HIV-1 Envelope proteins (gp120 and gp140). We have employed surface plasmon resonance, analytical sedimentation equilibrium analysis, isothermal titration calorimetry and atomic force spectroscopy to characterize the antigenicity and study the energetics, kinetics and single molecule force measurements of the binding of anti-gp120 and anti-gp41 antibodies to several recombinant HIV-1 Envelope proteins. These studies have relevance in immunogen design for generating anti-HIV vaccines.

Education and Training

  • Ph.D., University of Glasgow (Scotland), 1992

Publications

Shen, X, Dennison, SM, Liu, P, Gao, F, Jaeger, F, Montefiori, DC, Verkoczy, L, Haynes, BF, Alam, SM, and Tomaras, GD. "Prolonged exposure of the HIV-1 gp41 membrane proximal region with L669S substitution." Proceedings of the National Academy of Sciences of the United States of America 107, no. 13 (March 15, 2010): 5972-5977.

PMID
20231447
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Verkoczy, L, Diaz, M, Holl, TM, Ouyang, Y-B, Bouton-Verville, H, Alam, SM, Liao, H-X, Kelsoe, G, and Haynes, BF. "Autoreactivity in an HIV-1 broadly reactive neutralizing antibody variable region heavy chain induces immunologic tolerance." Proceedings of the National Academy of Sciences of the United States of America 107, no. 1 (January 2010): 181-186.

PMID
20018688
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Alam, SM, Morelli, M, Dennison, SM, Liao, H-X, Zhang, R, Xia, S-M, Rits-Volloch, S, Sun, L, Harrison, SC, Haynes, BF, and Chen, B. "Role of HIV membrane in neutralization by two broadly neutralizing antibodies." Proceedings of the National Academy of Sciences of the United States of America 106, no. 48 (December 2009): 20234-20239.

PMID
19906992
Full Text

Gao, F, Scearce, RM, Alam, SM, Hora, B, Xia, S, Hohm, JE, Parks, RJ, Ogburn, DF, Tomaras, GD, Park, E, Lomas, WE, Maino, VC, Fiscus, SA, Cohen, MS, Moody, MA, Hahn, BH, Korber, BT, Liao, H-X, and Haynes, BF. "Cross-reactive monoclonal antibodies to multiple HIV-1 subtype and SIVcpz envelope glycoproteins." Virology 394, no. 1 (November 2009): 91-98.

PMID
19744690
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Holl, TM, Kuraoka, M, Liao, D, Verkoczy, L, Moody, MA, Alam, M, Liao, H, Haynes, BF, and Kelsoe, GH. "P04-44. Generation of antibody responses to HIV-1 membrane proximal external region (MPER) antigen." Retrovirology 6, no. SUPPL. 3 (October 22, 2009).

Full Text

Desaire, H, Haynes, BF, Go, EP, Liao, H, Sutherland, LL, Chang, Q, Zhang, Y, Irungu, J, and Alam, SM. "P20-08. Glycosylation: An important factor in Env diversity." Retrovirology 6, no. SUPPL. 3 (October 22, 2009).

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Verkoczy, L, Diaz, M, Holl, TM, Ouyang, Y, Bouton-Verville, H, Alam, SM, Liao, H, Kelsoe, G, and Haynes, BF. "P04-26. Immunological tolerance prevents the expression of a broadly reactive neutralizing HIV-1 antibody." Retrovirology 6, no. SUPPL. 3 (October 22, 2009).

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Shen, X, Dennison, M, Gao, F, Montefiori, DC, Verkoczy, L, Haynes, B, Alam, M, and Tomaras, G. "OA021-04. HIV-1 gp41 envelope MPER mutation altered epitope conformation in lipid and increased sensitivity to 2F5 and 4E10 neutralizing antibodies." October 22, 2009.

Full Text

Verkoczy, L, Moody, MA, Holl, TM, Bouton-Verville, H, Scearce, RM, Hutchinson, J, Alam, SM, Kelsoe, G, and Haynes, BF. "Functional, non-clonal IgMa-restricted B cell receptor interactions with the HIV-1 envelope gp41 membrane proximal external region." Plos One 4, no. 10 (October 6, 2009): e7215-null.

PMID
19806186
Full Text

Dennison, SM, Stewart, SM, Stempel, KC, Liao, H-X, Haynes, BF, and Alam, SM. "Stable docking of neutralizing human immunodeficiency virus type 1 gp41 membrane-proximal external region monoclonal antibodies 2F5 and 4E10 is dependent on the membrane immersion depth of their epitope regions." Journal of Virology 83, no. 19 (October 2009): 10211-10223.

PMID
19640992
Full Text

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