Food genomics and multi-omics integration to objectively characterize healthy dietary patterns and their associations with cardiometabolic health - Project Summary Dr. Curtis Tilves, PhD, is a Research Associate at the Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center in the University of Colorado Anschutz Medical Campus. He seeks a K01 Award to obtain the skill set, knowledge, and mentored research experience critical for his transition to an independent scientist with a research program focused on using ‘omics to identify: 1) objective biomarkers of lifestyle factors that can be targeted for improving cardiometabolic health, 2) mechanisms of cardiometabolic disease, and 3) factors that explain heterogeneity of intervention effects. Essential components of his transition include training in (1) the ability to conduct and analyze clinical trials; (2) the expertise to generate, process, and analyze different types of ‘omics data; and (3) the machine learning skills to integrate multiple ‘omics measurements. The research in this K01 aims to leverage multiomics, including plant food genomics, to quantify plant food diversity and adherence to the cardioprotective Dietary Approaches to Stop Hypertension (DASH) diet and to use these objective ‘omics-estimated diet measures to understand how DASH can impact cardiovascular (CVD) health. Most epidemiologic evidence informing healthy dietary patterns come from self-reported dietary intake, which has substantial measurement error and systematic bias. Objective dietary biomarkers can overcome these limitations, and their identification remains a national high priority for nutritional research. High-dimensional ‘om- ics datasets (e.g., microbiome, metabolome) lack the sensitivity and specificity for characterizing diet. Residual plant food genomics in feces may provide more specific biomarkers for characterizing diet, but this has not been tested in a rigorous randomized feeding trial where food is provided and weight is isocalorically maintained. This K01 will leverage a randomized feeding trial of a DASH vs. typical U.S. diet (DASH for Diabetes, DASH4D) and a large observational cohort (Baltimore Longitudinal Study of Aging, BLSA) to (1) discover and validate individual and integrated ‘omics signatures (food genomic, microbiome, and metabolome) of plant food diversity and DASH diet, (2) examine these signatures vs self-reported diet with CVD risk factors, and (3) test if multiomics can predict and explain individual CVD responses to a DASH diet. Dr. Tilves will carry out this research in the rich training environment of the LEAD Center and the University of Colorado. He will be mentored by Dr. Noel Mueller, PhD, MPH (LEAD faculty and former K01 awardee), co- mentor Dr. Dana Dabelea, MD, PhD (Distinguished University Professor and Director of the LEAD Center), and a multidisciplinary team of scientific advisors. Dr. Tilves will also attend courses, workshops, seminars, scientific meetings, and participate in study meetings to further enhance his research and career development skills. This mentored K01 will allow Dr. Tilves to achieve his career training and research aims, and to grow into an inde- pendent researcher who leverages multi-omics to improve cardiometabolic health.
