Laurence A. Turka
Co-Director, Transplantation Biology Research Center
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 will examine the role of CD28 in Treg development, conversion, and survival, and its importance for maintaining established T effector driven immune respones. Initially this work will focus on transplantation models, but will then expand to other in vivo T cell responses.
A second program is the role of the tumor suppressor gene Pten in T cell development and T cell responses. Pten has multiple different functions, including regulating PI-3 kinase activity and genomic stability. Using mice with Pten deficiency targeted to specific T cell lineages, and knock-in mutants with specific domains inactivated, we are exploring the role this molecule in T cell homeostasis.
The last major focus is the role of Toll-like receptors (TLRs) expressed on T cells in cellular immune responses. New data from Dr. Turka's laboratory indicates that 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 metabolic studies, as well as 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.
Rahman AH, Cui W, LaRosa DF, Taylor DK, Zhang J, Goldstein DR, Wherry EJ, Kaech SM*, and Turka LA*. MyD88 plays a critical T cell-intrinsic role in supporting CD8 T cell expansion during acute LCMV infection. J Immunol 181:3804-3810, 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.
Last Update: 1/2/2013