Determining the role of the surface receptor T cell immunoglobulin and mucin domain three (TIM-3) in effector T cell responses

My research is currently focused on determining the role of T cell immunoglobulin and mucin domain three (TIM-3) in responses by effector T cells. Previous literature has found TIM-3 to be implicated in the negative regulation of T cells, specifically Th1 cells and CD8+ T cells through models of autoimmunity such as experimental autoimmune encephalomyelitis (EAE), multiple sclerosis, and diabetes. TIM-3 has been shown to induce apoptosis of Th1 cells and reduce IFNg production upon interaction with its ligand, galectin-9. I am particularly interested in 1) defining the molecular mechanisms that control the expression of TIM-3 by CD4+ and CD8+ T cells, 2) defining the downstream signaling events induced following TIM-3 engagement, and 3) determining the role of Tim-3 in modulating effector T cells responses to infectious challenge with Listeria monocytogenes.

Gorman JV, Colgan JD. Acute stimulation generates Tim-3-expressing T helper type 1 CD4 T cells that persist in vivo and show enhanced effector function. Immunology. 2018 Jul;154(3):418-433. doi: 10.1111/imm.12890. Epub 2018 Feb 8. PubMed PMID: 29315553; PubMed Central PMCID: PMC6002241.

Phong BL, Avery L, Sumpter TL, Gorman JV, Watkins SC, Colgan JD, Kane LP. Tim-3 enhances FcεRI-proximal signaling to modulate mast cell activation. J Exp Med. 2015 Dec 14;212(13):2289-304. doi: 10.1084/jem.20150388. PubMed PMID:26598760; PubMed Central PMCID: PMC4689164.

Gorman JV, Colgan JD. Response to Comment on "Tim-3 Directly Enhances CD8 T Cell Responses to Acute Listeria monocytogenes Infection". J Immunol. 2014 Jul 15;193(2):467-8. doi: 10.4049/jimmunol.1401297. PubMed PMID: 24994908.

Gorman JV, Colgan JD. Regulation of T cell responses by the receptor molecule Tim-3. Immunol Res. 2014 May 14. [Epub ahead of print] PubMed PMID: 24825777.

Gorman JV, Starbeck-Miller G, Pham NL, Traver GL, Rothman PB, Harty JT, Colgan JD. Tim-3 directly enhances CD8 T cell responses to acute Listeria monocytogenes infection. J Immunol. 2014 Apr 1;192(7):3133-42. doi: 10.4049/jimmunol.1302290. Epub 2014 Feb 24. PubMed PMID: 24567532; PubMed Central PMCID: PMC3965639.

Chiba S, Baghdadi M, Akiba H, Yoshiyama H, Kinoshita I, Dosaka-Akita H, Fujioka Y, Ohba Y, Gorman JV, Colgan JD, Hirashima M, Uede T, Takaoka A, Yagita H, Jinushi M. Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nat Immunol. 2012 Sep;13(9):832-42. doi: 10.1038/ni.2376. Epub 2012 Jul 29. PubMed PMID: 22842346; PubMed Central PMCID: PMC3622453.

Curtiss ML, Gorman JV, Businga TR, Traver G, Singh M, Meyerholz DK, Kline JN, Murphy AJ, Valenzuela DM, Colgan JD, Rothman PB, Cassel SL. Tim-1 regulates Th2 responses in an airway hypersensitivity model. Eur J Immunol. 2012 Mar;42(3):651-61. doi: 10.1002/eji.201141581. PubMed PMID: 22144095; PubMed Central PMCID: PMC3528103.