Michael L. Dustin

Muriel G. and George W. Singer Professor of Molecular Immunology; Professor, Skirball Institute of Biomolecular Medicine, Molecular Pathogenesis. Department of Pathology. Coord Molecular Pathogenesis Program

Ph.D., 1990 Harvard University

Lab Website: http://saturn.med.nyu.edu/research/mp/dustinlab

Keywords: Infection, Transplantation, Vaccination, Autoimmunity, Cancer

 

Contact Information: 

Skirball Institute of Biomolecular Medicine
540 First Avenue 2nd floor, Lab 4-5
New York, N.Y. 10016
Office Tel: (212) 263-3207
Lab Tel: (212) 263-3208
Fax: (212) 263-5711
E-mail: michael.dustin@med.nyu.edu

Administrative Contact:

Richard Stout
Tel: (212) 263-6282
Email: richard.stout@med.nyu.edu

 


Dynamics and Structure of Immunological Synapses

The focus of our lab is to understand basic aspects of T cell activation, particularly the role of the immunological synapse- a stable interaction between immune cells that mediates signaling and effector function. Major questions include how activation thresholds are set and how innate immune and environmental signals in tissues alter these thresholds. These questions are relevant to therapeutic strategies to boost the immune response in the context of vaccination, chronic infection and tumor immunotherapy and to suppress the immune response in the context of autoimmunity and transplantation.

My lab has taken two major approaches to these questions. In the first we have developed a technology for studying receptor-ligand interactions in a physiological, but highly controllable system using supported planar bilayers to replace one of the interacting cells. A second major area is to understand the manner in which environmental signals are integrated with signals from antigen receptors in secondary lymphoid tissues and other tissue sites based on intravital microscopy.

Recent finding in the first area include demonstration that autoreactive T cells have abnormal immunological synapses (Schubert et al., 2012) and demonstration that the human disc-large-1 tumor suppressor is critical for regulatory T cell immunological synapse function (Zanin-Zhorov et al., 2012). In the later area we have studied distinct migration modes for T cells in germinal center and following differentiation into plasma cells (Fooksman et al., 2010; Victora et al., 2010) and we have uncovered the mechanism by which radiation therapy and therapeutic antibodies synergize in a model for breast cancer (Ruocco et al., 2012).

Integration across the in vitro and in vivo studies will be very important to gain the maximum synergy between the two major approaches in the lab. Ongoing studies focus on area of autoimmunity, bacterial and viral infection and tumor immunotherapy will be complemented by new studies in parasitic infection and graft-versus host disease.

Selected Publications:

Fooksman, D.R., Schwickert, T.A., Victora, G.D., Dustin, M.L., Nussenzweig, M.C., and Skokos, D. (2010). Development and migration of plasma cells in the mouse lymph node. Immunity 33, 118-127. PMID: 20619695

Ruocco, M.G., Pilones, K.A., Kawashima, N., Cammer, M., Huang, J., Babb, J.S., Liu, M., Formenti, S.C., Dustin, M.L., and Demaria, S. (2012). Suppressing T cell motility induced by anti-CTLA-4 monotherapy improves antitumor effects. J. Clin. Invest. Oct 1; 122 (10):3718-30. PMID: 22945631

Schubert, D.A., Gordo, S., Sabatino, J.J., Jr., Vardhana, S., Gagnon, E., Sethi, D.K., Seth, N.P., Choudhuri, K., Reijonen, H., Nepom, G.T., et al. (2012). Self-reactive human CD4 T cell clones form unusual immunological synapses. J Exp Med 209, 335-352. PMID: 22312112

Victora, G.D., Schwickert, T.A., Fooksman, D.R., Kamphorst, A.O., Meyer-Hermann, M., Dustin, M.L., and Nussenzweig, M.C. (2010). Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter. Cell 143, 592-605. PMID: 21074050

Zanin-Zhorov, A., Lin, J., Scher, J., Kumari, S., Blair, D., Hippen, K.L., Blazar, B.R., Abramson, S.B., Lafaille, J.J., and Dustin, M.L. (2012). Scaffold protein Disc large homolog 1 is required for T-cell receptor-induced activation of regulatory T-cell function. Proc Natl Acad Sci U S A 109, 1625-1630. PMID:22307621

Click here to see all publications in PubMed