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

Alam, SM, Liao, H-X, Dennison, SM, Jaeger, F, Parks, R, Anasti, K, Foulger, A, Donathan, M, Lucas, J, Verkoczy, L, Nicely, N, Tomaras, GD, Kelsoe, G, Chen, B, Kepler, TB, and Haynes, BF. "Differential reactivity of germ line allelic variants of a broadly neutralizing HIV-1 antibody to a gp41 fusion intermediate conformation." J Virol 85, no. 22 (November 2011): 11725-11731.

PMID
21917975
Full Text

Tomaras, GD, Binley, JM, Gray, ES, Crooks, ET, Osawa, K, Moore, PL, Tumba, N, Tong, T, Shen, X, Yates, NL, Decker, J, Wibmer, CK, Gao, F, Alam, SM, Easterbrook, P, Abdool Karim, S, Kamanga, G, Crump, JA, Cohen, M, Shaw, GM, Mascola, JR, Haynes, BF, Montefiori, DC, and Morris, L. "Polyclonal B cell responses to conserved neutralization epitopes in a subset of HIV-1-infected individuals." J Virol 85, no. 21 (November 2011): 11502-11519.

PMID
21849452
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Liao, H-X, Chen, X, Munshaw, S, Zhang, R, Marshall, DJ, Vandergrift, N, Whitesides, JF, Lu, X, Yu, J-S, Hwang, K-K, Gao, F, Markowitz, M, Heath, SL, Bar, KJ, Goepfert, PA, Montefiori, DC, Shaw, GC, Alam, SM, Margolis, DM, Denny, TN, Boyd, SD, Marshal, E, Egholm, M, Simen, BB, Hanczaruk, B, Fire, AZ, Voss, G, Kelsoe, G, Tomaras, GD, Moody, MA, Kepler, TB, and Haynes, BF. "Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated." J Exp Med 208, no. 11 (October 24, 2011): 2237-2249.

PMID
21987658
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Verkoczy, L, Chen, Y, Bouton-Verville, H, Zhang, J, Diaz, M, Hutchinson, J, Ouyang, Y-B, Alam, SM, Holl, TM, Hwang, K-K, Kelsoe, G, and Haynes, BF. "Rescue of HIV-1 broad neutralizing antibody-expressing B cells in 2F5 VH x VL knockin mice reveals multiple tolerance controls." J Immunol 187, no. 7 (October 1, 2011): 3785-3797.

PMID
21908739
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Bonsignori, M, Hwang, K-K, Chen, X, Tsao, C-Y, Morris, L, Gray, E, Marshall, DJ, Crump, JA, Kapiga, SH, Sam, NE, Sinangil, F, Pancera, M, Yongping, Y, Zhang, B, Zhu, J, Kwong, PD, O'Dell, S, Mascola, JR, Wu, L, Nabel, GJ, Phogat, S, Seaman, MS, Whitesides, JF, Moody, MA, Kelsoe, G, Yang, X, Sodroski, J, Shaw, GM, Montefiori, DC, Kepler, TB, Tomaras, GD, Alam, SM, Liao, H-X, and Haynes, BF. "Analysis of a clonal lineage of HIV-1 envelope V2/V3 conformational epitope-specific broadly neutralizing antibodies and their inferred unmutated common ancestors." J Virol 85, no. 19 (October 2011): 9998-10009.

PMID
21795340
Full Text

Bonsignori, M, Wu, X, Moody, MA, Liao, H, Hwang, K, Crump, JA, Capiga, SH, Sam, NE, Tomaras, GD, Chen, X, Tsao, C, Alam, SM, Nabel, GJ, Kwong, PD, Morris, L, Montefiori, D, Mascola, JR, and Haynes, BF. "Isolation of CD4-Binding Site and V2/V3 Conformational (Quaternary) Broadly Neutralizing Antibodies from the Same HIV-1 Infected African Subject." October 2011.

Scholars@Duke

Cale, EM, Bazick, HS, Rianprakaisang, TA, Alam, SM, and Letvin, NL. "Mutations in a dominant Nef epitope of simian immunodeficiency virus diminish TCR:epitope peptide affinity but not epitope peptide:MHC class I binding." J Immunol 187, no. 6 (September 15, 2011): 3300-3313.

PMID
21841125
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Ma, B-J, Alam, SM, Go, EP, Lu, X, Desaire, H, Tomaras, GD, Bowman, C, Sutherland, LL, Scearce, RM, Santra, S, Letvin, NL, Kepler, TB, Liao, H-X, and Haynes, BF. "Envelope deglycosylation enhances antigenicity of HIV-1 gp41 epitopes for both broad neutralizing antibodies and their unmutated ancestor antibodies." Plos Pathog 7, no. 9 (September 2011): e1002200-null.

PMID
21909262
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Ferrari, G, Pollara, J, Kozink, D, Harms, T, Drinker, M, Freel, S, Moody, MA, Alam, SM, Tomaras, GD, Ochsenbauer, C, Kappes, JC, Shaw, GM, Hoxie, JA, Robinson, JE, and Haynes, BF. "An HIV-1 gp120 envelope human monoclonal antibody that recognizes a C1 conformational epitope mediates potent antibody-dependent cellular cytotoxicity (ADCC) activity and defines a common ADCC epitope in human HIV-1 serum." J Virol 85, no. 14 (July 2011): 7029-7036.

PMID
21543485
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Flynn, BJ, Kastenmüller, K, Wille-Reece, U, Tomaras, GD, Alam, M, Lindsay, RW, Salazar, AM, Perdiguero, B, Gomez, CE, Wagner, R, Esteban, M, Park, CG, Trumpfheller, C, Keler, T, Pantaleo, G, Steinman, RM, and Seder, R. "Immunization with HIV Gag targeted to dendritic cells followed by recombinant New York vaccinia virus induces robust T-cell immunity in nonhuman primates." Proc Natl Acad Sci U S A 108, no. 17 (April 26, 2011): 7131-7136.

PMID
21467219
Full Text

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