Caroline Fox received her B.A. in English and M.P.H. in epidemiology from the University of Michigan in 1991 and 1993, respectively, and her M.D. from the University of Pennsylvania in 1998. She completed her residency in internal medicine at the Brigham and Women's Hospital in 2001, and completed a fellowship in Endocrinology at the Brigham and Women's Hospital. In 2002, Dr. Fox joined the NHLBI's Framingham Heart Study as a Medical Officer and became a tenured Investigator in 2012. Currently, she has a joint appointment as an Associate Clinical Professor of Medicine in the Brigham and Women's Hospital Department of Endocrinology. Dr. Fox has received a NHLBI Director’s Award and two NHLBI Star Awards for her research and mentoring. She has published over 260 original scientific articles as well as several reviews and book chapters and is an associate editor for the journal Circulation. Dr. Fox is a member of the American Heart Association, Obesity Society, American Diabetes Association, American Society of Nephrology, and was recently inducted into the American Society of Clinical Investigators.
Chronic kidney disease (CKD) affects nearly 13% of the U.S. population and is an important risk factor for cardiovascular disease (CVD). Dr. Fox’s laboratory is interested in how CVD risk factors, particularly metabolic risk factors like obesity and diabetes, influence the pathogenesis of both CKD and CVD. Dr. Fox and her research team make use of cross-cutting, integrative research techniques including epidemiology, biomarker research, genetics, and genomics.
A major focus of the Dr. Fox’s research is exploring the genetic underpinning of CKD. In earlier work, her group identified a heritable component to both CKD and urinary albumin excretion. The laboratory is currently expanding on that discovery using state-of-the art unbiased approaches including genome-wide association studies (GWAS), targeted sequencing, and whole exome sequencing to uncover genetic loci for CKD and other renal traits. As part of this project, the Fox laboratory has convened CKDGen, an international GWAS consortium that brings together more than 25 population-based studies in order to share results and facilitate gene discovery. CKDGen has already uncovered dozens of novel loci for CKD, including more than 20 new loci associated with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD. The Fox laboratory is actively elucidating the mechanistic underpinning of some of these newly discovered loci. These findings will hopefully lead to the discovery of new pathways involved in disease pathogenesis. These functional experiments are leveraging the Framingham Heart Study’s SABRe project, a systems biology initiative that is identifying and validating new biomarkers for heart disease, metabolic syndrome, and diabetes.
A second major research area for the Fox laboratory focuses on adipose tissue deposition and obesity. Her laboratory has developed protocols to measure novel fat depots by computed tomography (CT), including subcutaneous, abdominal, pericardial, liver, perivascular, and renal sinus fat. Work is ongoing to understand the relationship between these metabolic fat depots, CVD risk factors, and the development of CVD. As an example, a recent study postulated hat periaortic fat volume affects the aortic dimensions in both the thorax and abdomen, supporting the idea that local fat depots may contribute to aortic remodeling. The Fox laboratory also focuses on the genetics and genomics of obesity and ectopic fat, via working with the study cohorts in the CHARGe and GIANT consortia.
Finally, the Fox laboratory studies diabetes as a significant CVD risk factor. Work here mostly focuses on using the tools of traditional epidemiology, especially the 60-year longitudinal data available from the Framingham Heart Study, which provides a rich dataset in which to explore long-term trends in diabetes. Through this combination of past and present, Dr. Fox hopes to uncover the connections between metabolism, CKD, and CVD.