Faculty

Karla Leavens, M.D., Ph.D.

Assistant Professor of Pediatrics (Endocrinology and Diabetes)

Department: Pediatrics

Graduate Group Affiliations

Contact information

Children's Hospital of Philadelphia
The Hub for Clinical Collaboration
Division of Endocrinology, 7th Floor
3500 Civic Center Blvd
Philadelphia, PA 19104

Office: 267-455-3727

Education:
BA (Biological Sciences)
Dartmouth College, 2003.
PhD (Cell and Molecular Biology)
University of Pennsylvania School of Medicine, 2010.
MD
University of Pennsylvania School of Medicine, 2012.

Permanent link

> Perelman School of Medicine > Faculty > Details

Description of Research Expertise

Research Interests: Using human cell models to study beta cell disease

Keywords: stem cells, diabetes, hyperinsulinism

Research Details: I am a physician-scientist at CHOP in pediatric endocrinology. My lab is using human stem cell-derived pancreatic beta cells to study monogenic beta cell diseases, including diabetes and hyperinsulinism. Our current focus is on HNF1A, which causes both hyperinsulinism in infancy and diabetes in adolescence and early adulthood through the same haploinsufficient mutations. We also have several other disease-causing genes in the pipeline, including HFN4A, a related transcription factor. By studying monogenic beta cell disease, we hope to expand our general knowledge of and contribute to the development of therapeutics that can treat and cure disease in the millions of people with more common forms of diabetes. In addition, now with stem cell-derived beta cells in clinical trials and posed to be approved as a cell-based curative therapy for individuals living with type 1 diabetes, we are involved in pre-clinical mechanistic studies on the implications of stem cell-derived beta cell transplant in pediatric recipients.

Rotation Projects:
- Knockdown of HNF1A and HNF4A using lentivirus in human islets
- Effects of HNF1A and HNF4A knockdown on insulin processing
- Role of IGF-1 signaling in stem cell-derived islets

Lab Personnel:
Francesca Perez Profeta- lab technician
Don Shelby- lab technician
Dorothy Asiedu- undergraduate
John Gonzalez- undergraduate

Selected Publications

Nahata L, Srinivasan S, Roche CI, Leavens KF, Kim MS, Levenson A, Topor LS, Singer K, McCormack S. : Measuring Up: Do Pediatric Endocrinology Fellows' Career Expectations Align with Workforce Reality? J Pediatrics 275(1): 114321, December 2024.

Leavens KF, Osorio-Quintero C, Yeuteuh EA, Perez-Profeta FT, Dattoli AA, Cardenas-Diaz FL, French DL, Gadue P: Generation of a fluorescent mNeonGreen insulin reporter line in the H1 (WA01) hESC background. Stem Cell Research 81(1): 103559, December 2024.

M. Craven, K. Lord, K. F. Leavens and D. D. De Leon: Insulin Immunoassay Interference Due to Human Antimouse Antibodies in a Patient With Ketotic Hypoglycemia. JCEM Case Reports 1(2): luad029, March 2023.

Karla F Leavens, Juan R Alvarez-Dominguez, Linda T Vo, Holger A Russ, Audrey V Parent: Stem cell-based multi-tissue platforms to model human autoimmune diabetes. Molecular Metabolism 66(1): 101610, Dec 2022 Notes: epub.

Tamaroff J, DeDio A, Wade K, Wells M, Park C, Leavens K, Rummey C, Kelly A, Lynch DR, McCormack SE: Friedreich's Ataxia related Diabetes: Epidemiology and management practices. Diabetes Res Clin Pract. 186(1): 109828, March 2022 Notes: epub.

George MN, Leavens KF, Gadue P: Genome Editing Human Pluripotent Stem Cells to Model β-Cell Disease and Unmask Novel Genetic Modifiers. Front Endocrinol (Lausanne). 2(12): 682625, June 2021 Notes: epub.

Wild KT, Nomakuchi TT, Sheppard SE, Leavens KF, De León DD, Zackai EH: Hyperinsulinism in an individual with an EP300 variant of Rubinstein-Taybi syndrome Am J Med Genet A 185(4): 1251-1255, April 2021.

Leavens KF and Wood A: Absent Thirst and Diabetes Insipidus. Diabetes Insipidus in Children, A Pocket Guide. Alter CA (eds.). Springer, 2021 Notes: Chapter.

Leavens KF, Liao CM, Gagne AL, Kishore S, Cardenas-Diaz FL, French DL, Gadue P: Generation of a double insulin and somatostatin reporter line, SCSe001-A-3, for the advancement of stem cell-derived pancreatic islets. Stem Cell Research 50(4): 102112, December 2020.

Cardenas-Diaz FL, Leavens KF, Kishore S, Osorio-Quintero C, Chen YJ, Stanger BZ, Wang P, French D, Gadue P: A Dual Reporter EndoC-βH1 Human β-Cell Line for Efficient Quantification of Calcium Flux and Insulin Secretion. Endocrinology 161(2): bqaa005, Feb 1 2020.