Elaine Reed, PhD
Dr. Elaine Reed's research efforts are focused on understanding the mechanism of organ allograft rejection. The development of anti-HLA antibodies following transplantation is associated with transplant vasculopathy, a manifestation of chronic allograft rejection. Reed and colleagues postulate that HLA antibodies are pathogenic in chronic rejection by binding to HLA class I and class II molecules on endothelium of the allograft and transducing signals that stimulate pathological changes within the microvasculature that are characteristic of acute and chronic allograft rejection. The researchers' studies have shown that binding of antibodies to distinct HLA class I and class II molecules on endothelial cells triggers a series of intracellular signaling cascades resulting in endothelial cell activation, migration, proliferation and enhanced leukocyte recruitment. These studies suggest HLA antibodies can play a key role in the development of intimal hyperplasia associated with chronic rejection of human allografts. Current efforts are focused on elucidating the co-receptors that cooperate with HLA molecules to elicit pathogenic signals contributing to rejection. Understanding these mechanisms 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 assessment of the healthy versus unhealthy immune system in various immune and inflammatory disorders. She and her associates are developing assays to measure immune function and use these tests to predict disease susceptibility across age, race ethnicities and gender. In collaboration with researchers in UCLA's liver transplant program, the Reed lab is developing immune profiles of transplant recipients at risk of liver ischemia reperfusion injury and transplant rejection. Together with UCLA's heart failure program, she is developing tests to characterize different immune cell subsets in the peripheral blood to predict which patients are going to develop multi-organ failure. Reed is collaborating with researchers in the UCLA adult and pediatric transplant programs to define humoral immune responses to HLA and non-HLA ligands that mediate acute and chronic rejection. The researchers are expanding this work to develop proteomic biomarkers for the early detection of cardiac, lung, renal and liver transplant rejection.
Wozniak LJ, Hickey MJ, Venick RS, Vargas JH, Farmer DG, Busuttil RW, McDiarmid SV, Reed EF. Donor-specific HLA Antibodies Are Associated With Late Allograft Dysfunction After Pediatric Liver Transplantation. Transplantation. 2015 Jul;99(7):1416-22. doi: 10.1097/TP.0000000000000796.
Valenzuela NM, Trinh KR, Mulder A, Morrison SL, Reed EF. Monocyte recruitment by HLA IgG-activated endothelium: the relationship between IgG subclass and Fc-gamma-RIIa polymorphisms. Am J Transplant. 2015 Jun;15(6):1502-18. doi: 10.1111/ajt.13174. Epub 2015 Feb 3.
Bondar G, Cadeiras M, Wisniewski N, Maque J, Chittoor J, Chang E, Bakir M, Starling C, Shahzad K, Ping P, Reed E, Deng M. Comparison of whole blood and peripheral blood mononuclear cell gene expression for evaluation of the perioperative inflammatory response in patients with advanced heart failure. PLoS One. 2014 Dec 17;9(12):e115097. doi: 10.1371/journal.pone.0115097. eCollection 2014.
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. doi: 10.1126/scisignal.2001158.
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.