Dr. De León-Crutchlow’s research focuses on the pathophysiology of monogenic disorders of insulin regulation resulting in hyper- and hypoglycemia, the role of the entero-insular axis, and how these mechanisms can be applied toward developing novel therapies.

The laboratory contributions from the examination of human islets isolated from surgical specimens from infants with congenital hyperinsulinism provide novel pathophysiological insights. A particular interest of Dr. De León-Crutchlow involves examining the interactions between the gut and pancreatic beta cell under pathologic conditions.

She demonstrated that the GLP-1 receptor is constitutively active in pancreatic islets isolated from a mouse model of hyperinsulinism (SUR-1-/-), and that pharmacologic antagonism of the GLP-1 receptor (GLP-1R) ameliorates hypoglycemia in SUR-1-/- mice and blunts abnormalities of insulin secretion in cultured mouse and human hyperinsulinism islets.

Dr. De León-Crutchlow is the lead investigator of several clinical studies on exendin-(9-39) as a novel therapy for congenital hyperinsulinism. From examining the phenotype of affected patients and human islets, she has provided novel insights into the pathophysiology of hyperinsulinism. Particularly important findings have been the functional, genomics, and metabolomics characterization of hyperinsulinism islets; the description of a novel syndrome of hyperinsulinism and hypopituitarism caused by a mutation in FOXA2; and the association of hyperinsulinism with mutations in the transcription factors HNF1A and HNF4A, which were previously known to cause monogenic diabetes and with Beckwith Wiedemann Syndrome caused by paternal uniparental disomy of 11p15.5. A better understanding of the pathophysiology and the molecular mechanisms of disease will facilitate the development of new therapeutics and a personalized approach to treatment of children with hyperinsulinism.

Dr. De León-Crutchlow also examines novel mechanisms of disease affecting insulin regulation and resulting in diabetes. Contributions from her laboratory include describing neonatal diabetes due to inactivating mutations in neurogenin-3, activating KATP channel mutations, and inactivating mutations of GATA6.

MD, University of Panama (1992)

MSCE, University of Pennsylvania (Clinical Epidemiology/Clinical Trials), 2012

Chief of the Division of Endocrinology and Diabetes

Director, Congenital Hyperinsulinism Center

Distinguished Chair in the Department of Pediatrics

Attending Physician

Professor of Pediatrics

American Diabetes Association, 2002-

The Endocrine Society, 2002-

Pediatric Endocrine Society, 2003-

Society for Pediatric Research, 2010-

Center of Excellence Faculty Scholar, University of Pennsylvania, 2003

Fellow, Arab-American Frontiers of Science, Engineering, and Medicine Symposium. Kuwait Institute for Scientific Research, Kuwait, U.S. National Academies, 2011

Fellow, Japanese-American Kavil Frontiers of Science Symposium. Irvine, California, U.S. National Academies and the Japan Society for the Promotion of Science, 2012

CHOP Congenital Hyperinsulinism Center