Genetic determinants of thoracic aortic stiffness and remodeling

Project Summary / Abstract This is an application for a K24 mentoring award for patient-oriented research (POR) from Julio Chirinos, MD, PhD, Associate Professor of Medicine at the Perelman School of Medicine at the University of Pennsylvania (Penn). Dr. Chirinos‘ long-term goals are to: (1) Substantially contribute to our understanding and approaches to

the prevention and treatment of aortic aging and its associated disease burden, and; (2) to mentor the next generation of investigators interested in the epidemiology of aortic aging and its consequences in human health. This mid-career development award will be critical to help him achieve these goals via dedicated/protected time

for mentoring activities, research and development of new skills that are anticipated to greatly enhance the

applicant’s impact in this field throughout the rest of his career, as well as the impact and success of his trainees. The candidate has a strong record of mentorship, leadership, and research productivity. His research program encompasses epidemiologic, translational and POR studies of arterial aging and its role in Heart Failure with

Preserved Ejection Fraction (HFpEF) and other conditions that afflict our aging population. The scientific goal of this proposal is to investigate the genetic determinants of age-related thoracic aortic stiffening and elongation using large available biobanks with associated genomic and aortic imaging data. These include the UK Biobank

and the Penn Medicine Biobank. The projects will include the application of a novel method for quantification of

aortic pulse wave velocity that can, for the first time, be applied retrospectively in widely available clinical imaging studies. Deep learning for high-throughput aortic phenotyping will play an important role in this research. The mentoring goals of this application are to engage and support the training of Penn fellows and junior faculty to

conduct POR in arterial aging. The career development goal of this application is to support the candidate’s professional development and acquisition of new skills for POR research in aging, specifically: (1) genomics (genome-wide association studies, next generation sequencing, and Mendelian Randomization); (2) Applied

deep learning to leverage large banks of imaging data in order to accomplish accurate high-throughput phenotyping of aortic aging. This will be achieved through formal training courses and engaging in sustained collaboration experiences with experts in these topics. The candidate will also engage in career development

and promotion of arterial aging research through convening scientific meetings on aortic aging research and improving the national network of POR research in arterial aging through existing professional societies. The institutional environment for clinical and translational science at Penn is outstanding. The Department of

Medicine at Penn has made a substantial commitment, including protected time and dedicated space, toward the candidate’s sustained success as a patient-oriented researcher responsible for training a new generation of junior investigators who conduct research in older participants.