Principal Investigator

Michael R. Elliott, Ph.D. University of Rochester work Box 609 601 Elmwood Ave Rochester NY 14642 office: KMRB 3-9625 p (585) 273-4793

Regulation of leukocyte motility by ELMO family proteins

Time-lapse imaging of CD4+ T cells from wild-type (WT, CFSE) and Elmo1-/- (KO, TAMRA) crawling on a glass dish coated with ICAM-1 and CCL21.

Mammalian ELMO proteins (ELMO1-3, Engulfment and Cell Motility) are a family of evolutionarily conserved cytoplasmic adaptor proteins that bind to Dock proteins to promote the activation of the small GTPase Rac – a critical regulator of actin polymerization, cell shape and motility. Using Elmo1-deficient mice we have recently discovered a critical and non-redundant role for Elmo1 in regulating chemotaxis of naïve T cells to CCR7 and CXCR4 ligands.

The overall goal of this project is to understand how Elmo1 functions to promote T cell migration and what role Elmo1 plays in T cell trafficking during adaptive immune responses. We have several active areas of investigation related to Elmo1 function: 1) determine how Elmo1 functions within T cells to integrate extracellular cues to affect cytoskeletal changes and cell migration, 2) assess the unique and overlapping functions of the three mammalian ELMO family members in lymphocytes, 3) determine the role of Elmo1 in controlling T cell migration into tissues during an immune response. These studies are aimed at developing new approaches to target the Elmo-Dock-Rac module to control T cell trafficking in diseased tissues.

References

1

Stevenson C, de la Rosa G, Anderson CS, Murphy PS, Capece T, Kim M and Elliott MR. Essential role of Elmo1 in Dock2-dependent lymphocyte migration. Journal of Immunology, 192:6062 (2014).

2

Elliott MR, Zheng S, Park D, Woodson RI, Reardon MA, Juncadella IJ, Kinchen JM, Zhang J, Lysiak JJ and Ravichandran KS. Unexpected requirement for ELMO1 in clearance of apoptotic germ cells in vivo. Nature, 467:333 (2010).

3
Park D, Tosello-Trampont AC, Elliott MR, Lu M, Haney LB, Ma Z, Klibanov AL and Ravichandran KS. Brain-specific angiogenesis inhibitor 1 (BAI1) is a novel engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature 450:430 (2007).

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