Mentored Patient-Oriented Research in Natriuretic Peptide System Based Precision Cardiometabolic Health - PROJECT SUMMARY Dr. Pankaj Arora is an Associate Professor of Medicine (Tenured), the Director of the Cardiovascular Genomics Clinic, and the Director of the Clinical and Translational Research Program at the University of Alabama at Birmingham (UAB). His ultimate career goal is to establish a Center for Precision Medicine that will provide multidimensional training incorporating clinical epidemiology, big data analysis, designing and conducting clinical trials, genomic studies, and precision medicine to young trainees to develop them into well-rounded physician- scientists. He has established a successful, federally-funded (3 R01 awards) laboratory that focuses on assessing the genetic determinants of natriuretic peptide (NP) levels, unraveling the pathophysiological pathways through which NPs cause cardiometabolic disease, and developing targeted approaches centered on the NP system to treat cardiometabolic diseases. Apart from NP-based projects, his research team has a consistent output of mentee-led projects ranging from epidemiological studies on cardiovascular health to the disparities in clinical outcomes in cardiovascular diseases, which have been published in prestigious journals. Dr. Arora has trained >20 mentees at various career stages, including undergraduate students, medical students, residents, cardiology fellows, and T32 fellows. The K24 award will provide Dr. Arora with protected time to mentor trainees and develop individualized plans to help his mentees achieve their research career goals. He would also work on improving his mentorship skills through the experiences of his mentorship team, comprised of previous K24 awardees with decades of mentorship experience, and through formal didactics on mentorship offered by the UAB Center Clinical and Translational Science. Furthermore, he will expand his research focus to include advanced genomics, proteomics, and implementation science. Dr. Arora will learn specialized genetic analytic techniques (rare and structural variant analyses) and gain hands-on experience in conducting targeted mass spectrometry to study the bioactive levels of NPs. Recognizing the challenges of implementing the results of research in clinical practice, Dr. Arora will attend didactics and work with an implementation scientist to devise a plan for the clinical implementation of polygenic risk scores in the Cardiogenomics Clinic. Dr. Arora proposes 3 unique projects that cover the range of clinical research including a post-hoc analysis of an ongoing R01 study to assess the racial differences in response to NP augmentation on correcting a non-dipping BP profile, examine the bioactive levels of NPs and their response to physiological perturbations using blood samples collected in 2 R01 studies, and determining the contribution of genomics to NP levels using data from a multi-ethnic cohort of US individuals. Therefore, these projects would not only expand the current knowledge on NPs and their role in cardiometabolic disease but also provide mentees with unparalleled training in clinical research.