The applicant is a nephrology fellow interested in studying kidney disease using proteomic techniques that can be transitioned into clinical practice to aid with diagnosis and disease management. The applicant's long-term goal is to successfully use proteomics to identify early markers of kidney disease that he can use to better understand mechanisms of kidney disease and halt progression to end-stage kidney disease. This application proposes a career development plan that will transition the applicant to an independent investigator in proteomics and kidney disease. Briefly, the training program of the application includes formal coursework in the fields of statistics, bioinformatics, and clinical trial design while incorporating mentored guidance from Dr. Hassan Ibrahim, Division of Renal Diseases and Hypertension and Dr. Gary Nelsestuen, Director of the Center for Mass Spectrometry and Proteomics at the University of Minnesota. The applicant also outlines the outstanding environment at the University of Minnesota for career development and research. The immediate goal of the applicant is to identify urinary markers of interstitial fibrosis/tubular atrophy (IF/TA) in the kidney allograft, a major problem in transplantation leading to graft loss. The applicant proposes to study this by studying two groups of kidney transplant recipients at the University of Minnesota. The first group includes a 154 kidney transplant recipients enrolled in a clinical trial looking specifically at IF/TA. This study has prospectively collected urine samples over 5 years specifically for future proteomic studies such as the one proposed. The second group includes kidney transplant recipients with graft deterioration and renal biopsy data for correlative analyses. The applicant proposes to use matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) and ITRAQ analyses to do focused studies on the urine for biomarkers implicated in IF/TA. The applicant, under the guidance of Dr. Nelsestuen, has shown early data suggesting these techniques to be effective in following stable transplant recipients and that these techniques can detect changes in proteins associated with graft deterioration.
The results of this study will provide further insight into IF/TA and provide biomarkers that may assist clinicians in treating a growing problem in kidney transplantation.
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