This K23 grant proposal describes a research training plan geared to develop the junior faculty member into an independent physician scientist over the next five years. The principal investigator has completed training in Internal Medicine, a general nephrology fellowship and an AST/ASN accredited renal transplant fellowship followed by two years of laboratory training. This training plan will allow the PI to extend upon the scientific findings outlined in the preliminary data and obtain the requisite skills needed to successfully become an independent investigator. The research topic approaches the growing problem of chronic allograft rejection, focusing on autoimmunity as a complementary mechanism to alloimmunity in the development of chronic rejection, and takes advantage of serum samples and biopsy specimens collected through NIH studies run by the mentor and collaborators. The project is thus both novel and feasible. To address the hypothesis, the PI proposes the following 3 specific aims: 1) To assess the impact of inflammation and early allograft injury on the peripheral autoantibody repertoire;2) To characterize the autoantibody repertoires in transplant recipients with chronic allograft injury;and 3) To test whether posttransplant autoantibodies bind to allograft expressed antigens. The project will be mentored by Peter Heeger MD, a leader in the field of transplant biology with experience in mentoring more than 20 post doctoral fellows and K awardees. An advisory committee composed of physician scientists and PhD scientists will provide complementary guidance, all of whom have 10+ years of experience in their respective fields. To enhance the training, the PI will receive formal didactic training in immunology and biostatistics/bioinformatics, attend weekly journal clubs and present her work at Immunology Works in Progress Seminars as well as Transplant and Medicine Grand Rounds. Mount Sinai provides an outstanding environment for translational research with over 200 renal transplants performed annually, collaborators with extensive experience in human transplant trials, and extensive resources for technical and statistical support. This environment maximizes the potential of the PI to successfully develop into an independent investigator. Chronic rejection is the number one reason kidney transplants fail, leaving thousands of patients to return to dialysis since there is a limited pool of organ donors. Understanding how reactivity to self proteins influences long term transplant failure and what specific proteins are targeted will help us develop new therapies to improve health.
Chronic rejection is the number one reason kidney transplants fail, leaving thousands of patients to return to dialysis since there is a limited pool of organ donors. Understanding how reactivity to self proteins influences long term transplant failure and what specific proteins are targeted will help us develop new therapies to improve health.