Laurence A. Turka
Co-Director, Transplantation Biology Research Center
Harold and Ellen Danser Professor of Surgery
Transplantation Biology Research Center
13th Street, Building 149-9019
Boston, MA 02129
Our research program is based on cellular and molecular aspects of T cell tolerance, with a particular interest in mechanisms of transplant tolerance. Three major research areas are ongoing:
Our laboratory was the first to show that blockade of CD28 signals can prevent allograft rejection. Using new conditional CD28 knockout mice just generated in our lab and various Cre strains, we are examining the role of CD28 in Treg development, conversion, and survival, and its importance for maintaining established T effector driven immune respones, including transplantation, autoimmunity, and helper dependent antibody production. A second program is the role of the PI3 kinase pathway in regulatory T cells. The tumor suppressor gene Pten, a lipid phosphatase, is the primary negative regulator of PI3K in T cells. Using mice with Pten deficiency targeted to Tregs, as well as chemical inhibitors of PI3K, we are examining the role of PI3K in regulatory T cell homeostasis.
Coupled to this project are studies of T cell metabolism as modulated by PI3K, and the degree to which glycolysis vs. oxidative metabolism can dictate T cell fate and function. The last major focus is the role of Toll-like receptors (TLRs) and the coupled adaptor protein MyD88 in T cells. TLRs are expressed on activated T cells and provide survival and costimulatory signals and may regulate cellular energy utilization pathways and thus fate determination. These observations are currently being explored in vivo models of immune responses such as infection and transplantation using T cell specific MyD88-deficient animals.
Gelman AE, LaRosa DF, Zhang J, Walsh PT, Choi Y, Sunyer O, and Turka LA. The adaptor molecule MyD88 activates PI-3 kinase signaling in CD4(+) T cells and enables CpG oligodeoxynucleotide-mediated costimulation. Immunity 25:783-793, 2006.
Walsh PT, Buckler JL, Zhang J, Gelman AE, Dalton NM, Taylor DK, Bensinger SJ, Hancock WW, and Turka LA. PTEN regulates the IL-2 receptor responsiveness of CD4+CD25+ regulatory T cells. J Clin Invest 116:2521-2531, 2006.
Porrett PM, Yuan X, LaRosa DF, Walsh PT, Yang J, Gao W, Li P, Zhang J, Ansari JM, Hancock WW, Sayegh MH, Koulmanda M, Strom TB, and Turka LA. Mechanisms underlying blockade of allograft acceptance by TLR ligands. J Immunol 181:1692-1699, 2008.
Liu X, Karnell JL, Yin B, Zhang R, Zhang J, Li P, Choi Y, Maltzman JS, Pear WS, Bassing CH, and Turka LA. Distinct roles for PTEN in prevention of T cell lymphoma and autoimmunity in mice. J Clin Invest 120:2497-507, 2010.
Rahman, A.H., Zhang, R., Blosser, C.D., Hou, B., DeFranco, A.L., Maltzman, J.S., Wherry, E.J., and L.A. Turka: Anti-viral memory CD8 T cell differentiation, maintenance and secondary expansion occur independently of MyD88. Blood 117:31233130, 2011.
Zhang R, Huynh A, Whitcher G, Chang J, Maltzman JS, and Turka LA. An obligate cell-intrinsic function for CD28 in regulatory T cells. J Clin Invest 123:580-93, 2013.
Last Update: 1/6/2014