Michael L. Dustin
Research Professor of Pathology, Skirball Institute of Biomolecular Medicine, Cellular Dynamics. Department of Pathology
Ph.D., 1990 Harvard University
Cancer, Infection, Transplantation, Vaccination, Autoimmunity
Skirball Institute of Biomolecular Medicine
540 First Avenue 2nd floor, Lab 6
New York, N.Y. 10016
Cell: (646) 232-8091
Lab Tel: (212) 263-1469
Fax: (212) 263-5711
Tel: (212) 263-6282
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.
In 2013 most of my lab moved to the Kennedy Institute of Rheumatology at the University of Oxford. My efforts at Skirball continue with two students collaborating with Tom Neubert and Juan Lafaille. Recent work from the lab includes description of early transcriptional events in T cell activation with the Immunological genome consortium (IMMGEN), the discovery of synaptic ectosomes (initially referred to as extracellular vesicles) released into the immunological synapse with David Stokes and a collaborative effort with teams in Manchester and Glasgow to describe CD8 T cell dependent pathological events in experimental cerebral malaria. The current focus of lab members at Skirball is to determine the physiological significance of pre-mitotic cytotoxicity through immunological synapses in CD8 T cells and the broader roles of protein ubiquitination in T cell activation through proteomics and mouse genetics.
- Best JA, Blair DA, Knell J, Yang E, Mayya V, Doedens A, Dustin ML, Goldrath AW. Transcriptional insights into the CD8(+) T cell response to infection and memory T cell formation. Nat Immunol. 2013;14(4):404-12. Epub 2013/02/12. doi: 10.1038/ni.2536. PubMed PMID: 23396170
- Choudhuri K, Llodra J, Roth EW, Tsai J, Gordo S, Wucherpfennig KW, Kam LC, Stokes DL, Dustin ML. Polarized release of T-cell-receptor-enriched microvesicles at the immunological synapse. Nature. 2014;507(7490):118-23. Epub 2014/02/04. doi: 10.1038/nature12951. PubMed PMID: 24487619
- Shaw TN, Stewart-Hutchinson PJ, Strangward P, Dandamudi DB, Coles JA, Villegas-Mendez A, Gallego-Delgado J, van Rooijen N, Zindy E, Rodriguez A, Brewer JM, Couper KN, Dustin ML. Perivascular Arrest of CD8+ T Cells Is a Signature of Experimental Cerebral Malaria. PLoS Pathog. 2015;11(11):e1005210. doi: 10.1371/journal.ppat.1005210. PubMed PMID: 26562533