Dr. Sarah Wernimont

Obstetrics & Gynecology
Medical School
Twin Cities
Project Title: 
Metabolic Control of Trophoblast Differentiation

Gestational diabetes increases maternal risk of pregnancy complications and offspring risk for lifelong metabolic disease. There is an unmet need to identify strategies beyond glucose control to improve maternal and offspring health in gestational diabetes. Pregnancies complicated by gestational diabetes have abnormalities in placental development including defects in trophoblast differentiation. The mechanisms driving these abnormalities and clinical impact are not fully understood. As dynamic hubs of cellular regulation, mitochondria do more than generate ATP via oxidative phosphorylation. In response to nutrient availability and cellular demands, mitochondria direct entry and exit of metabolites from the inner mitochondrial membrane through regulated networks of mitochondrial transport proteins. This allows mitochondria to direct carbon resources to support diverse cellular functions including energy generation, gene expression, and cellular differentiation. Cellular citrate is a critical node of metabolic regulation, linking carbon obtained from glucose and glutamine to cytoplasmic acetyl-CoA pools. These acetyl Co-A pools contribute to histone acetylation and gene regulation. How citrate is regulated in trophoblasts and how cellular citrate pools are altered in response to substrate availability is not understood. Using metabolomics, RNA sequencing, CHIP sequencing and now spatial transcriptions, the researchers seek to define how mitochondrial transport proteins regulate trophoblast differentiation. This information is expected to identify new mechanistic opportunities to improve placental and fetal health in pregnancies complicated by gestational diabetes.

Project Investigators

Dr. Juan Abrahante Llorns
Micah Gearhart
Dr. Sarah Wernimont
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