The primary research goal of our laboratory is to define the biochemical, molecular and functional nature of antigenic peptides presented in the context of HLA class I antigens and evaluate their clinical significance. Studies are focused on peptides involved in renal allograft rejection, and human cancers. Tissue specific T cell clones also have been isolated from allograft biopsies of acutely rejecting kidneys, suggesting that T cells specific for kidney peptides may play a role in allograft rejection. We also are investigating the immunopathogenesis of bronchiolitis obliterans syndrome following clinical lung transplantation. Molecular as well as cellular immune mechanisms leading to obliterative airway disease also are studied using a murine model of tracheal transplantation.
The increasing shortage of donor organs for transplantation has led to a search for suitable xenograft organs. Pigs are now considered the primary candidate donor animals. It is generally accepted that natural antibodies and complement play a major role in xenograft rejection. We are investigating the mechanism of activation of endothelial cells by anti-MHC antibodies and its consequences on endothelial functions. In addition, we are defining the cellular immune mechanisms leading to rejection in porcine xenografts.
A third area of interest in the laboratory is in islet cell transplantation for patients suffering from type 1 diabetes. Methods to improve human islet cell isolation are being investigated. Studies also are ongoing to understand the immunological mechanisms of islet allograft rejection.
JDFI - Human Islet Distribution Program at the DRTC of Washington University
JDFI - Washington University Center for Islet Cell Transplantation
NIH - Immune mechanisms of rejection in human lung allografts
NIH - Pathogenesis of post-transplant bronchiolitis obliterans
NIH - DRTC Program Project - Islet Core Facility
NIH - Human Islet Isolation Program at Washington University
Goodman J, McKane BW, Mohanakumar T. Current issues in xenotransplantation. GRAFT. 2002;(5)1:34-38.
McKane BW, Trulock EP, Patterson GA, Mohanakumar T. Lung transplantation and bronchiolitis obliterans: An evolution in understanding. Immunologic Research. 2001;24:123-136.
Reznik SI, Jaramillo A, SivaSai KSR, et al. Indirect allorecognition of mismatched donor HLA class II peptides in lung transplant recipients with bronchiolitis obliterans syndrome. American Journal of Transplantation. 2001;1(3):228-235.
Smith CR, Jaramillo A, Tu Y, et.al. CD4+ T cell recognition of a single mismatched HLA-A2 transgenic molecule through the indirect antigen presentation pathway induces rejection of murine cardiac allografts. Transplantation. 2001;71(11):1640-1648.
Xu XC, Goodman J, Sasaki H, Lowell J, Mohanakumar T. Activation of natural killer cells and macrophages by porcine endothelial cells augments specific T cell xenoresponse. American Journal of Transplantation. 2002;2(4):314-322.
Lu KC, Jaramillo A, Mendeloff EN, Huddleston CB, Sweet SC, Patterson GA, Mohanakumar T. Concomitant allorecognition of mismatched donor HLA class I- and II-derived peptides in pediatric lung transplant recipients with bronchiolitis obliterans syndrome. Journal of Heart and Lung Transplantation. (in press)
Pub Med page for Thalachallour Mohanakumar, Ph.D.