About Us

Over the past two decades, our studies have focused on common, complex forms of cardiovascular/metabolic disorders, including atherosclerosis, fatty liver disease, and, more recently, heart failure. We have used population-based approaches in both animal models and humans as well as experimental studies in mice. Human genome-wide association studies in large human populations have revolutionized our understanding of common diseases, but in addition to the identification of causal genes we are interested an understanding of the higher-order interactions. To dissect such interactions, we use a systems biology perspective, integrating clinical trait phenotypes with genetic, epigenetic, transcriptomic, proteomic, and metabolomic high-throughput data.

To model common human genetic variation under specific environmental conditions, we have developed a reference resource, called the Hybrid Mouse Diversity Panel (HMDP), that consists of a panel of about 100 well characterized inbred strains of mice. As compared to human studies, the panel has the advantage of replication, access to relevant tissues and control of environmental factors. The panel has now been extensively characterized for clinical traits and multiple high throughput “omics” phenotypes. To complement the studies in mice, we investigate publicly available data and participate in studies of well-characterized human cohorts, including METSIM and STARNET.

A recent application of our “systems genetics” approach is the use of expression data from multiple tissues in the HMDP to identify novel endocrine-like interactions. We used the approach to identify coagulation factor 11 as a key mediator of crosstalk between liver and heart in both mice and humans and showed that deficiencies of factor 11 contribute to a common form of heart failure (Cao et al.. Science, 2022). Other recent applications of systems genetics approach include the identification of novel pathways contributing to metabolic syndrome (Chella Krishnan et al. Nat Metab., 2021) and fatty liver disease (Hui et al. Cell Mol Gastroenterol Hepatol., 2023).