|Institution||School of Medicine and Dentistry|
|Address||University of Rochester Medical Center|
School of Medicine and Dentistry
601 Elmwood Ave, Box SURG
Rochester NY 14642
||Star Award for Excellence in Graduate School Teaching
University of Massachusetts|
Dr. Miller-Graziano's laboratory has 3 NIH supported projects to assess different aspects of immunopathology in burn and trauma patients. A dysfunction in patient monocyte (MO) to dendritic (DC) cell differentiation has been identified along with a decrease in the immune stimulatory capacity of patients' MO. The current MO experiments focus on the tolerogenic capacity of patients' DC in mediating their immunodepression. Microarray analysis of DC derived from patients' dysfunctional, patients' immunostimulatory, controls' immunostimulatory and in vitro induced controls' tolerogenic populations is under way. Altered signaling proteins and receptor expression in these 2 patient and 2 control DC populations is being characterized by multicolor flow cytometry, Luminex, and RealTime PCR technology. These DC experiments particularly emphasize increases in co-inhibitory receptors like PD-L1+2, ILT3+4, and HEMV concomitant to decreases in costimulatory receptors like CD40, CD86, and CD80 as mechanisms behind dysfunctional MO/DC antigen presenting function in the immunodepressed patients. Autocrine inhibitory signaling by SIPR(alpha), CD47 and thrombospondin in patients' DC is also being assessed for their role in mediating MO driven decreased immune function post injury. The ability of patient DC to alter the responses of an HLA unrestricted, tetanus toxoid responsive, human T cell clone provides an additional assay for patient DC tolerogenic function.
A complimentary project investigates induction and maintenance of T cell adaptive tolerance as a contributor to post injury immunosuppression. An increased threshold of inhibitory signal transduction molecules and negative costimulation molecules appears to mediate some of the patients' T cell immunodepression. The induction of DC tolerogenic capacity by post injury apoptotic T cells and hyporesponsive T cells is also a focus of laboratory experiments. These 3 projects offer students an opportunity to apply fundamental immunologic principles and systems to the study of human immunopathology.
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