Currently, Dr. Elaine Reed's research efforts are focused on understanding the mechanism of chronic allograft rejection. The development of anti-HLA antibodies following transplantation is associated with transplant atherosclerosis, a manifestation of chronic allograft rejection. Reed and her colleagues postulate that anti-HLA antibodies are pathogenic in chronic rejection by binding to HLA class I molecules on endothelium and smooth muscle of the allograft and transducing signals that stimulate cell proliferation. The researchers' studies have shown that when anti-HLA antibodies bind to distinct HLA-A and -B locus molecules on endothelial and smooth muscle cells, there is increased tyrosine phosphorylation of intracellular proteins, induction of fibroblast growth factor receptor expression and cell proliferation. These studies suggest anti-HLA antibodies can play a key role in the initiation of proliferative signals, which stimulate the development of myointimal hyperplasia associated with chronic rejection of human allografts. Current efforts are focused on elucidating the class I signal transduction pathway. Understanding this mechanism will permit the development of new therapeutic modalities for the treatment and prevention of transplant atherosclerosis and the extension of functional life of transplanted organs.
An additional focus of Reed's research is in the development of methods for immunologic evaluation of the immune response in transplant patients. She and her associates are developing assays to measure both the humoral and cellular alloimmune response to the graft. These tests include monitoring of anti-HLA antibodies to identify patients at risk of rejection, monitoring the T-cell indirect allorecognition pathway for the diagnosis of chronic rejection and the study of immune and inflammatory gene expression during allograft rejection. The researchers are expanding this work to develop genomic and proteomic biomarkers for the early detection of cardiac, lung, renal and liver transplant rejection.
Selected Cancer-Related Publications:
Zhang X, Rozengurt E, Reed EF. HLA class I molecules partner with integrin Beta-4 to stimulate endothelial cell proliferation and migration. Sci Signal. 2010 Nov 23;3(149):ra85.
Bonagura VR, Du Z, Ashouri E, Luo L, Hatam LJ, DeVoti JA, Rosenthal DW, Steinberg BM, Abramson AL, Gjertson DW, Reed EF, Rajalingam R. Activating killer cell immunoglobulin-like receptors 3DS1 and 2DS1 protect against developing the severe form of recurrent respiratory papillomatosis. Hum Immunol. 2010 Feb;71(2):212-9. Epub 2009 Oct 25.
Li F, Atz ME, Reed EF. Human leukocyte antigen antibodies in chronic transplant vasculopathy-mechanisms and pathways. Curr Opin Immunol. 2009 Oct;21(5):557-62. Epub 2009 Sep 11.
Jindra PT, Jin YP, Rozengurt E, Reed EF. HLA class I antibody-mediated endothelial cell proliferation via the mTOR pathway. J Immunol. 2008 Feb 15;180(4):2357-66.
Jindra PT, Hsueh A, Hong L, Gjertson D, Shen XD, Gao F, Dang J, Mischel PS, Baldwin WM 3rd, Fishbein MC, Kupiec-Weglinski JW, Reed EF. Anti-MHC class I antibody activation of proliferation and survival signaling in murine cardiac allografts. J Immunol. 2008 Feb 15;180(4):2214-24.