Research Abstract:
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. We are also investigating the immunopathogenesis of bronchiolitis obliterans syndrome following human lung transplantation. Molecular as well as cellular immune mechanisms leading to obliterative airway disease are being studied using a murine model of tracheal transplantation.
The increasing shortage of donor organs for transplantation has lead to a search for suitable xenografts organs. Pigs are now considered the primary candidate donor animal. We are examining the role of cellular rejection in xenografts. Studies are also in progress to determine tumor antigenic peptides for human breast and lung cancers. We have identified HLA-A2 and HLA-A3 restricted antigenic peptides derived from a breast cancer associated protein Mammaglobin-A. Furthermore, we have shown the efficacy of vaccination against Mammaglobin-A to generate a strong Cytotoxic T cell response that can regress breast cancer in an in vivo mouse model. We are also in the process of studying the role of Tensacin-C in immune evasion and tumor progression of human lung cancer.
Selected Publications:
Bharat A, Fields RC, Trulock EP, et. al. Induction of IL-10 suppressors in lung transplant patients by CD4+25+ regulatory T cells through CTLA-4 signaling. J Immunology 2006 177:5631-5638.
Kuo E, Bharat A, Shih J, et al. Role of airway epithelial injury in murine orthotopic tracheal allograft rejection. Ann Thorac Surg 2006 82:1226-1233.
Mohanakumar T, Narayanan K, Desai N, et al. A significant role for histocompatibility in human islet transplantation. Transplantation 2006 82:180-187.
Ramachandran S, Desai NM, Gores TA, et al. Improved islet yields from pancreas preserved in perflurocarbon is via inhibition of apoptosis mediated by mitochondrial pathway. Amer J Transplant 2006 6:1696-1703.
Narayanan K, Jaramillo A, Benshorr ND et al. Regression of established human breast tumors induced by vaccination with mammaglobin-A cDNA. J Natl Cancer Inst 2004 96:18:1388-1396.
Last Updated: 09/07/2007 |