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Pinney Laboratory
The Pinney lab is currently investigating how intrauterine growth restriction, gestational diabetes, and in utero exposure to environmental toxicants including bisphenol A (BPA), bisphenol S (BPS) and perfluorooctanoic acid (PFOA) contribute to the development of diabetes and obesity in the offspring. The research team works with human samples, animal models, and cell culture systems to study molecular mechanisms, including epigenetic modifications responsible for fetal programming of adult metabolic disease. Specifically, the lab is investigating the molecular mechanisms that are responsible for the development of diabetes, non-alcoholic fatty liver disease, and obesity after exposure to an altered intra-uterine milieu.
A second focus of Dr. Pinney’s research program is identifying and treating children with Atypical Diabetes, including monogenic forms of diabetes with the aim to develop targeted novel approaches to treatment for this population. Dr. Pinney and her colleagues in the Diabetes Center for Children at CHOP have identified and treated children and adolescents with 12 different forms of monogenic diabetes. Her lab is actively working to better understand the clinical features and molecular mechanisms responsible for these rare forms of diabetes in children, in order to develop novel treatment strategies to benefit all patients with diabetes.
Project Highlights
- Measured concentrations of the endocrine disruptor bisphenol A (BPA) in human amniotic fluid, and reported that amniotic fluid BPA concentrations are associated with decreased birth weight.
- Correlated amniotic fluid BPA concentrations with genome wide DNA methylation patterns and gene expression profiles via RNA-Seq in corresponding amniocytes, a fetal-derived cell with stem cell properties, and found that male offspring are more affected by in utero BPA exposure than female offspring.
- Characterized the metabolome, transcriptome, and methylome of second trimester amniotic fluid and term placenta exposed to gestational diabetes.
- Made the seminal observation that intrauterine growth restriction (IUGR)-induced epigenetic modifications can be reversed by Exendin-4, a drug used to treat type 2 diabetes in the human, thereby normalizing the phenotype.
- Described a new form of monogenic diabetes due to a recessive mutation in Neurogenin-3 and a novel form of dominant congenital hyperinsulinism that maps to chromosome 10q21 at the Hexokinase 1 locus (Pinney SE et al. J Clin Endocrinol Metab 2011; Pinney SE, Hormone Research in Paediatrics, 2013).
Leader
Sara E. Pinney, MD, MS
Attending Physician
Dr. Pinney investigates the molecular mechanisms that link an adverse intrauterine milieu to the development of diabetes and obesity later in life. Specifically, she is researching how intrauterine growth restriction, gestational diabetes and in utero exposure to environmental toxicants contribute to the development of diabetes and obesity in offspring.