Caitlyn E. Bowman-Cornelius

Scholarship/Creative Work

My research interests include quantifying macronutrient metabolism and deciphering metabolic flexibility in health and disease at the levels of mitochondrial, cellular, and whole-organismal metabolism. I am specifically interested in the metabolic changes that occur during mammalian pregnancy—a time of incredible metabolic demand that may serve as a stress test exacerbating a mother’s pre-existing conditions, introducing pregnancy-specific complications, or precipitating metabolic disease later in life. In addition, fetal development is especially sensitive to maternal nutrition yet remarkably able to adapt. The Bowman Lab uses biochemistry and analytical chemistry to characterize metabolic adaptations during pregnancy and early postnatal life. This work includes quantifying macronutrient use and characterizing metabolic regulation in mouse models and cultured cells.

Maternal-Fetal Metabolic Communication

In utero and early-life nutrition impacts health outcomes in childhood and beyond in complex, interconnected ways that researchers are only just beginning to understand. Maternal-fetal metabolic communication is the bidirectional communication of nutritional status and metabolic demand by various modes including circulating metabolites, endocrine molecules, and other secreted factors to coordinate maternal and fetal metabolism in response to nutrient status. The balance of fetal demand and maternal need is perhaps most precarious in late gestation. During my graduate training in the laboratory of Dr. Michael Wolfgang, I used pregnant mouse models to uncover examples of late-gestation metabolic communication between mother and fetus. These signals and responses were amplified by maternal fasting and by genetic impairment of maternal mitochondrial metabolism. This work demonstrated a fundamental role for maternal metabolic factors in mediating the fetal response to nutrient deprivation. My postdoctoral work in the laboratory of Dr. Zolt Arany at the University of Pennsylvania, Perelman School of Medicine, continued along this line of investigation, and I developed mouse models and analytical chemistry methods to quantitatively interrogate maternal macronutrient utilization during late gestation.

The Bowman Lab is continuing to explore mechanisms of metabolite exchange that convey information and mediate responses to stimuli such as nutrient sufficiency or deficiency. The placenta is the maternal-fetal interface that participates in metabolite exchange plus metabolic and hormonal signaling, and we are studying models of placental metabolism and transplacental transport.

Cardiovascular Adaptations in Pregnancy

Maternal heart increases in size during pregnancy in a process known as physiological hypertrophy. A similar yet molecularly distinct process happens to the heart with exercise training. We are investigating molecular changes in the vasculature during late pregnancy that occur concomitantly with maternal heart remodeling. The vasculature has direct access to—and mediates transport of—circulating molecules that participate in signaling. For this reason, we are excited to study the function of several genes that we have found to be significantly regulated in maternal vasculature during pregnancy.

Selected Publications

Complete list of publications

Original Research

Pre-print:

Bowman CE*, Neinast MD*, Forelli N, Jang C, Patel J, Blair MC, Mirek ET, Jonsson WO, Chu Q, Merlo L, Mandik-Nayak L, Anthony TG, Rabinowitz JD, Arany Z. (2024) Off-target depletion of plasma tryptophan by allosteric inhibitors of BCKDK. bioRxiv. 10.1101/2024.03.05.582974.

Berger JH, Matsuura TR, Bowman CE, Taing R, Patel J, Lai L, Leone TC, Reagan JD, Haldar SM, Arany Z, and Kelly DP. (2024) Sodium-glucose co-transporter 2 inhibitors act independently of SGLT2 to confer benefit for heart failure with reduced ejection fraction in mice. bioRxiv. 10.1101/2024.04.29.591665.

Kim B, Zhao W, Coffey NJ, Bowman CE, Noji M, Jang C, Simon MC, and Arany Z. (2024) HIF2α-dependent inhibition of mitochondrial clustering of glutaminase suppresses clear cell renal cell carcinoma. bioRxiv. 10.1101/2024.05.04.592520.

Published:

Bowman CE, Selen Alpergin ES, Cavagnini K, Smith DM, Scafidi S, and Wolfgang MJ. Maternal lipid metabolism directs fetal liver programming following nutrient stress. Cell Rep (2019) 29, 1299-1310.

Bowman CE, Selen Alpergin ES, Ellis JM, and Wolfgang MJ. Loss of ACOT7 potentiates seizures and metabolic dysfunction. Am J Physiol Endocrinol Metab (2019) 317, E941-E951.

Bowman CE, Rodriguez S, Selen Alpergin ES, Acoba MG, Zhao L, Hartung T, Claypool SM, Watkins PA, and Wolfgang MJ. The mammalian malonyl-CoA synthetase ACSF3 is required for mitochondrial protein malonylation and metabolic efficiency. Cell Chem Biol (2017) 24, 673-684.

Jernberg JN, Bowman CE, Wolfgang MJ, and Scafidi S. Developmental regulation and localization of carnitine palmitoyltransferases (CPTs) in rat brain. J Neurochem (2017) 142, 407-419.

Bowman CE, Zhao L, Hartung T, and Wolfgang MJ. Requirement for the mitochondrial pyruvate carrier in mammalian development revealed by a hypomorphic allelic series. Mol Cell Biol (2016) 36, 2089-2104.

Ellis JM, Bowman CE, and Wolfgang MJ. Metabolic and tissue-specific regulation of acyl-CoA metabolism. PLoS One (2015) 10, e0116587.

Reviews and Commentaries

Bowman CE, Arany Z, and Wolfgang MJ. Regulation of maternal-fetal metabolic communication. Cell Mol Life Sci (2021) 78, 1455-1486.

Bowman CE and Arany Z. The newborn heart GLAdly benefits from maternal milk. J Cardiovasc Aging (2023) 3, 35.

*These authors contributed equally