Mentoring & Patient-Oriented Research in Sickle Cell-Related Kidney Disease - The overall goal of this K24 application titled “Mentoring & Patient-Oriented Research in Sickle Cell-Related Kidney Disease” is for a mid-career hematologist and physician-scientist, Santosh L. Saraf, MD, to develop necessary skills to mentor the next generation of junior investigators focused on sickle cell disease (SCD)- related research. Chronic kidney disease develops in over half of adults with SCD and leads to increased morbidity and early mortality. The mechanisms for how chronic kidney disease develops are, unfortunately, poorly understood and therapies to prevent and treat sickle cell nephropathy are urgently needed. Further complicating the care of individuals with sickle cell disease is the dearth of clinicians focused on SCD-related research and clinical care. The applicant’s goals for this K24 award are to train the next generation of clinician scientists by leveraging preliminary work and multi-center collaborations of carefully phenotyped SCD cohorts to identify high-risk patients and targetable pathways for SCD-related kidney disease. The applicant has demonstrated that chronic exposure of the kidneys to cell-free hemoglobin and heme are associated with progression of chronic kidney disease. The new research that is proposed in this award is a natural extension of Dr. Saraf’s ongoing work and consists of investigating 1) whether genetic variation of the haptoglobin allele and heme oxygenase-1 GT-repeats predicts chronic kidney dysfunction and its progression and 2) if complement activation is implicated in the pathophysiology of cell-free hemoglobin catabolism and SCD- related kidney disease. Several of Dr. Saraf’s active and completed projects have developed longitudinal SCD cohorts with harmonized phenotypes, including kidney, heart and lung function. These cohorts are available for mentees to address the research aims in this proposal as well to develop their respective independent research trajectories. Dr. Saraf will apply several resources available at the University of Illinois at Chicago, such as T35, TL1, R38, and KL2 programs, to train and produce outstanding clinical scientists. Dr. Saraf has a strong record of funded clinical research and mentoring trainees but requires additional protected time and training to become an inspiring mentor for this underserved and high-risk patient population. The K24 award will provide Dr. Saraf with the additional time and resources to amplify his efforts in understanding risk factors and targetable pathways for SCD-related chronic kidney disease and in training the next generation of clinician scientists in SCD-related research and clinical care.
