Instructor in Pediatrics
Pediatrics Critical Care
Jennifer Duncan, M.D. and Sarah England, Ph.D.
Dr. Brookheart grew up with both parents serving in the US Army and spent her childhood living throughout the United States, Asia, and Europe. This unique experience helped foster her scientific curiosity and an appreciation for creative solutions to common problems.
As a Sweet Briar College undergraduate she was inducted into Phi Beta Kappa and spent her junior year at the University of St. Andrews in Scotland. She graduated from Sweet Briar magna cum laude in 2003.
In 2009, Dr. Brookheart received her Ph.D. in the laboratory of Dr. Jean E. Schaffer at Washington University in St. Louis and later pursued her postdoctoral studies with Dr. Peter J. Espenshade at Johns Hopkins University School of Medicine. In 2014, she joined the laboratory of Dr. Jennifer Duncan at Washington University in St. Louis and in 2015 accepted a faculty position from the Department of Pediatrics at Washington University in St. Louis.
Dr. Brookheart’s professional interests include the discovery of previously unknown metabolic disease mechanisms that will help develop therapies leading to improved patient quality of life.
Dr. Brookheart’s biomedical research career began while an undergraduate at Sweet Briar College, where she was awarded a minority research grant from a state non-profit to test the selectivity and efficacy of novel anti-cancer drugs on human leukemia cell lines. During this time, she developed a strong foundation in cell culture and fluorescence microscopy. As a summer undergraduate, Dr. Brookheart researched transformation of primary fibroblasts by the Human Papilloma Virus at the University of Rochester in the laboratory of Dr. Dennis J. McCance. It was during her senior year; however, that she was introduced to metabolic research through a collaboration with the Division of Endocrinology and Metabolism at the University of Virginia to investigate pancreatic 13-cell differentiation. This collaboration was made possible by a research grant she was awarded from her undergraduate institution.
Dr. Brookheart’s doctoral thesis work in the laboratory of Dr. Jean E. Schaffer at Washington University in St. Louis was the first description of a feed-forward loop mechanism between a non-coding RNA and general oxidative stress. Her research also demonstrated a requirement for non-coding RNAs in the cellular response to lipid overload, which led to a first author publication in the Journal of Biological Chemistry, a publication in Cell Metabolism, and a review on lipotoxicity for Cell Metabolism. Her work received an NIH F31 Predoctoral NRSA award and an NIH Supplement to Promote Diversity in Health Related Research.
Dr. Brookheart began her postdoctoral position in the lab of Dr. Peter J. Espenshade at Johns Hopkins University. She was awarded an NIH F32 Postdoctoral NRSA grant and characterized a new binding protein of the master sterol regulating transcription factor SREBP in fission yeast and mammals.
After completing her research at Johns Hopkins, Dr. Brookheart joined the laboratory of Dr. Jennifer Duncan at Washington University in St. Louis to investigate the impact of maternal diet on ovarian mitochondrial function and offspring health using Drosophila melanogaster.
Awards and Honors
2011-2013 NRSA Individual Postdoctoral Fellowship (F32), NIH
2006-2008 NRSA Minority Individual Predoctoral Fellowship (F31), NIH
Impact of insulin signaling on ovarian mitochondrial function and offspring metabolism
On average, a quarter of all pregnant women in the United States are obese, putting them at increased risk for preeclampsia and miscarriage. Additionally, the offspring of these women are more susceptible to developmental anomalies and long-term metabolic complications later in life, including obesity, type 2 diabetes, and cardiovascular disease. Using an established Drosophila melanogaster model of maternal obesity, this proposal demonstrates that adult females fed a high sucrose diet exhibit insulin resistance and altered ovarian size and mitochondrial function. Furthermore, offspring of maternally obese flies have altered metabolism and impaired mitochondria, which corroborate findings in both animal and epidemiological studies. Insulin resistance has been linked to mitochondrial disruption in obese and type 2 diabetic patients and components of the insulin signaling pathway have been implicated in altering mammalian mitochondrial function. However, conflicting data exists on whether insulin resistance contributes to or is caused by mitochondrial dysfunction. ! hypothesize that caloric excess in females results in impaired insulin signaling that contributes to ovarian size and mitochondrial dysfunction and disrupts offspring mitochondrial and metabolic function. I propose to test this hypothesis in the fly maternal obesity model by specifically focusing first on elucidating the role of insulin resistance on ovarian size and mitochondrial function by performing carefully executed time-course experiments to determine the time of onset of insulin resistance and mitochondrial impairment in obese females and using insulin signaling mutants to determine whether insulin resistance is causal to or exacerbates ovarian mitochondrial disruption. Second, I will investigate the impact of maternal insulin resistance on offspring metabolism and mitochondrial function by altering maternal insulin signaling and assessing body composition and measuring ATP/ADP levels and oxidative phosphorylation of ovarian mitochondria . 0. melanogaster is an ideal model organism for these pursuits because of its highly tractable genetics, ease of dietary manipulations, and conservation of metabolic regulatory factors and the insulin signaling pathway. This proposal aims to elucidate the molecular mechanisms contributing to diet-induced maternal and offspring abnormalities, which is of paramount importance to women’s reproductive health.