Our research program is centered on genomics, especially immunogenomics, to better understand the interplay of genetic and environmental factors in the development of diabetes, atherosclerosis, and Alzheimer’s disease. We have been leading the genome-wide association study of Health, Aging and Body Composition (Health ABC) cohort, a population-based, multi-ethnic, and prospective cohort of 3,000 elders. We also led or participated in a number of national and international GWASs and pharmacogenomics consortia. Our grant, Epigenomic Study of Atherosclerosis in the Multi-ethnic Study of Atherosclerosis (MESA, N=2,800), funded through NIH RoadMap Epigenomics Initiatives in 2009, has enabled us to collect and purify high quality CD14+ monocytes and CD4+ T cells from fresh blood draw at MESA exam 5 (2010-2012) in four communities. Our group is among the first to show that immunogenomics (e.g., DNA methylomics and transcriptomics) of purified disease-relevant cells in a large cohort (e.g., circulating monocytes from ~1260 subjects) has robust power and promise to discover the biology of inflammatory diseases. These published works have yielded new genes and gene pathways potentially causal to diabetes and CVD, which are being evaluated as drug targets.
Our work in this area has been continuously funded by several NIH grants, including a randomized clinical trial grant. The aims of the grants are to assess the predictive power of the identified genomic features on the incidence of inflammatory diseases, and better understand the causes and consequences of the identified genomic features. We are also examining the causes of longitudinal changes of the genomic features by repeating the epigenomics and transcriptomics profiling of monocytes at MESA exam 6. Our current projects focus on the roles of transcriptomics, epigenomics (e.g., DNA methylation, histone modification, chromatin accessibility, et.al.), and non-coding RNAs (in particular microRNAs, enhancer RNAs) in various tissue/cell types (including monoctyes, macrophages, T cells, and adipocytes), using state-of- the-art sequencing and new single-cell genomic technologies. We also conduct mechanistic and functional studies (in vitro and in vivo experiments) to follow up on most promising signals from population-based observational studies.