Project Summary / Abstract Healthy diets reduce the risk of cardiovascular disease (CVD). Plant-based diets, which are comprised predominantly of plant foods and are low in animal products, are healthy dietary patterns that are associated with a lower risk of CVD. However, the precise mechanisms underlying plant-based diet-CVD associations are poorly understood. The present proposal aims to elucidate the mechanisms through which plant-based diets are associated with CVD using proteomics and epigenetics. Specific aims of the present proposal are to: 1) identify protein signatures of 4 plant-based diet indices [overall plant-based diet index (PDI), provegetarian diet, healthy plant-based diet index (hPDI), and unhealthy plant-based diet index (uPDI)], 2) evaluate the prospective associations between plant-based diet-related proteins and incident CVD, and 3) explore DNA methylation signatures of 4 plant-based diet indices. The proposed study will use the Atherosclerosis Risk in Communities (ARIC) study, a richly phenotyped community-based prospective study of middle-aged African American and European American with usual dietary intake, proteomics and DNA methylation data, and adjudicated CVD outcomes as the discovery data set. Framingham Heart Study and Multi-Ethnic Study of Atherosclerosis, well-characterized prospective cohorts with similar data, will be used for external validation. Completion of the aims will identify novel proteins, epigenetic markers, and pathways that are modifiable by plant-based diets. Such novel evidence will be the first step for developing biomarkers for early detection and identifying therapeutic targets of CVD. Hyunju Kim, PhD seeks a K01 Mentored Research Scientist Development Award to acquire essential skills, knowledge, and mentored research experience to prepare for a future career as an independent investigator with expertise in nutrition, multi-omics, and CVD. Dr. Kim has a track record of research productivity in the areas of nutritional epidemiology and nutritional metabolomics. However, Dr. Kim needs additional training in proteomics, epigenetics, and cardiovascular biology to achieve research independence. This research proposal details a five-year plan consisting of didactic coursework, hands-on research training, career enrichment programs under the primary mentorship of Dr. Casey Rebholz, PhD (expert in nutritional proteomics), and co-mentorship by Dr. Josef Coresh, MD, PhD (expert in proteomics and vascular disease), and Dr. Dan Arking, PhD (expert in epigenetics). The exceptional mentoring team in addition to external collaborators and advisors with multi-disciplinary expertise, and a highly collaborative environment at Johns Hopkins Bloomberg School of Public Health will ensure the successful transition of Dr. Kim into an independent investigator.

Project Narrative Plant-based diets are healthy dietary patterns that are consistently associated with a lower risk of cardiovascular disease (CVD) and CVD risk factors. The proposed research seeks to uncover the mechanisms underlying plant-based diets and CVD by comprehensively characterizing the proteome and methylome, and integrating multiple omics data from 3 large prospective cohorts. The proposed research will yield novel evidence on protein markers and epigenetic markers of plant-based diets, and pathways linking plant-based diets to CVD, thus providing a basis to formulate CVD prevention and treatment strategies.