Dr. Fox works in three major content areas: obesity, diabetes, and chronic kidney disease. Her work spans traditional population science and genetic epidemiology. In terms of obesity, Dr. Fox is interested in body fat distribution and ectopic fat depots. As such, Dr. Fox has created a computed-tomography body composition database by using standard imaging techniques to assess abdominal visceral fat, pericardial fat, mediastinal fat, perivascular fat, fatty liver, and renal sinus fat. Her work focuses on both the systemic and local manifestations of body fat distribution, working with the concept that fat can have locally toxic effects on the vasculature and nearby anatomic structures. A cornerstone of Dr. Foxs work in this area has revolved around the mentoring of students, pre-doctoral fellows, post-doctoral fellows, and junior faculty members. These datasets have resulted in 11 publications in the past year. Dr. Fox is also involved in the genetics and genomics of obesity and body composition. She leads the CHARGE adiposity group, and is an active participant in the GIANT consortium, a genome-wide association consortium dedicated to uncovering genomic loci for anthropometric traits. The GIANT consortium has recently uncovered 14 new loci for body fat distribution and 18 new loci for body mass index. Because genome-wide association identifies single nucleotide polymorphisms that are common, sequencing studies can help uncover rare variants. As part of the CHARGE-S consortium, sequencing is ongoing for generalized obesity and body composition. Dr. Fox also works to understand the role of chronic kidney disease. Dr. Fox is interested in traditional and novel risk factors for chronic kidney disease. Chronic kidney disease is an important risk factor for heart disease, and often is undetected. Thus, improving our ability to detect and predict chronic kidney disease is an important scientific goal. The Fox lab has recently developed a renal risk score, and showed that novel biomarkers can improve our ability to predict who will develop kidney disease within a 10-year interval. Urinary biomarkers can provide insight into risk prediction, but also provide information regarding the location of renal injury, which may have prognostic significance. The Fox lab is now examining a panel of 14 urinary biomarkers. Parallel to epidemiologic and biomarker work, Dr. Fox leads the CHARGE renal working group, a consortium which focuses on the genetics of renal function. In the past year, this work has lead to the discovery of 5 new genes for uric acid, 13 genes for chronic kidney disease, 5 loci for serum magnesium, and 1 for serum calcium. Dr. Fox is also the founder and convener of CKDGen, an international consortium dedicated to uncovering genes for renal disease. CKDGen includes more than 25 participating studies with over 70,000 individual participants and 60 investigators. This group is rapidly working to uncover even more genes for kidney disease. This work has also evolved into sequencing, and the CHARGE-S consortium is sequencing 400 cases of chronic kidney disease. Finally, because genome-wide association offers a statistical association only, Dr. Fox has set up a collaboration with a zebra fish lab to begin to understand the functional consequences of some newly uncovered loci for renal function. Finally, Dr. Fox works in the area of diabetes, primarily to understand trends in diabetes as a risk factor for heart disease, as well as treatment patterns over time. Other members of the Fox lab include: 1) Dr. Conall OSeaghdhea is a post-doctoral fellow in the Fox lab. As a nephrologist, his work focuses on chronic kidney disease. He has worked with Dr. Fox to develop a risk score for chronic kidney disease, as well as novel biomarkers for kidney disease. 2) Meredith Foster is a PhD student at the Harvard School of Public Health carrying out her doctoral work in the Fox lab. She has worked with Dr. Fox to develop a protocol to measure renal sinus fat on computed tomography, and related this measure in particular to hypertension and chronic kidney disease.
| Mellinger, Jessica L; Pencina, Karol M; Massaro, Joseph M et al. (2015) Hepatic steatosis and cardiovascular disease outcomes: An analysis of the Framingham Heart Study. J Hepatol 63:470-6 |
| Shungin, Dmitry (see original citation for additional authors) (2015) New genetic loci link adipose and insulin biology to body fat distribution. Nature 518:187-196 |
| Yeoh, Aaron J; Pedley, Alison; Rosenquist, Klara J et al. (2015) The Association Between Subcutaneous Fat Density and the Propensity to Store Fat Viscerally. J Clin Endocrinol Metab 100:E1056-64 |
| Fox, Caroline S; Bonaca, Marc A; Ryan, John J et al. (2015) A randomized trial of social media from Circulation. Circulation 131:28-33 |
| Long, Michelle T; Wang, Na; Larson, Martin G et al. (2015) Nonalcoholic fatty liver disease and vascular function: cross-sectional analysis in the Framingham heart study. Arterioscler Thromb Vasc Biol 35:1284-91 |
| Abraham, Tobin M; Pencina, Karol M; Pencina, Michael J et al. (2015) Trends in diabetes incidence: the Framingham Heart Study. Diabetes Care 38:482-7 |
| Musani, Solomon K; Fox, Ervin R; Kraja, Aldi et al. (2015) Genome-wide association analysis of plasma B-type natriuretic peptide in blacks: the Jackson Heart Study. Circ Cardiovasc Genet 8:122-30 |
| Rosenquist, Klara J; Massaro, Joseph M; Pedley, Alison et al. (2015) Fat quality and incident cardiovascular disease, all-cause mortality, and cancer mortality. J Clin Endocrinol Metab 100:227-34 |
| Murabito, Joanne M; Pedley, Alison; Massaro, Joseph M et al. (2015) Moderate-to-vigorous physical activity with accelerometry is associated with visceral adipose tissue in adults. J Am Heart Assoc 4:e001379 |
| Raghavan, Sridharan; Porneala, Bianca; McKeown, Nicola et al. (2015) Metabolic factors and genetic risk mediate familial type 2 diabetes risk in the Framingham Heart Study. Diabetologia 58:988-96 |
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