Patient-Oriented Research for Cardiometabolic Health in Children

PROJECT SUMMARY The goal of this K24 Midcareer Investigator Award in Patient-Oriented Research is to enhance the ability of Dr. Miriam Vos to train, mentor, and support new investigators in patient-oriented research in the field of early cardiometabolic disease. The wide accessibility of dietary sugars in childhood has contributed to the childhood onset of insulin resistance, central weight gain, dyslipidemia, and hepatic steatosis. One of the most important questions is the reversibility of cardiometabolic disease in children – particularly with interventions in the pre- pubertal time period before adult phenotype weight gain occurs. My short-term research goals are to understand the physiologic changes in children that lead to metabolic dysfunction-associated steatotic liver disease (MASLD, formerly named NAFLD) onset and to test sugar reduction as a prevention for MASLD and the accompanying insulin resistance and dyslipidemia. My long-term research goals are to develop an evidence base that will lead to public health campaigns to reduce the prevalence and severity of MASLD in children and to advance the field toward precise nutrition recommendations for children, targeted to their physiologic and genetic propensities. These goals align with the NHLBI Strategic Vision Objective 3, including identifying the causes of CVD health differences. My prior experience in clinical trials in children, with embedded mechanistic studies, my leadership in clinical and translational research, and my collaborations with leading experts in body composition assessment, omics, machine learning, and genetics provide an exceptional milieu for new investigators. This K24 application will provide protected time to devote specifically to mentoring new investigators in patient- oriented research (POR) in the prevention of cardiometabolic disease in children, to support mentee career advancement, and to nurture their growth into independent investigators. This proposal describes an existing portfolio of funded research including the R01-funded clinical trial “Prevention of Pediatric MASLD in Hispanic Children” that creates opportunities for ancillary research projects for mentees. New research is proposed to explore genetic-environment interactions as drivers of cardiometabolic health in Hispanic/Latino children. The Aims of this proposal are: 1) To increase mentoring of new investigators, particularly clinical fellows, and early career faculty, 2) To facilitate patient-oriented research addressing childhood onset cardiometabolic disease and MASLD, and 3) To support career development activities for the applicant including experience in NIH training grants, training in leadership and the advancement of persons underrepresented in medicine and training in the application of genetics in POR. Together, the proposed research, mentoring activities, and career development activities will expand the discovery of effective prevention strategies for cardiometabolic disease in children.