Jake Kushner
Assistant Professor, Dept of Pediatrics

Cell Biology and Physiology Program

Address

Children's Hospital of Philadelphia
Division of Endocrinology, ARC 802c
3615 Civic Center Blvd.
Philadelphia, PA 19104

Office tel.: 267-426-5717
Lab tel.: 215-590-4572
Fax: 215-590-1605
E-mail: kushnerj@mail.med.upenn.edu

Link

Dr. Kushner's Lab webpage

EDUCATION

University of California at Berkeley: BA (Biochemistry), 1993.

Albany Medical College: MD, 1994.

Brown University: Pediatrics Resident, 1994-1997.

Children's Hospital, Boston: Clinial Fellow (Pediatric Endocrinology), 1997-2000.

Havard Medical School: Postdoctoral Research Fellow, 1999-2003.

RESEARCH INTERESTS

• molecular regulation of cell cycle, adult beta- cell replication.

Key words: diabetes, development, cell cycle, cyclins, islets, stem cells, cancer.

Search PubMed for articles

DESCRIPTION OF RESEARCH

Islets of Langerhans secrete insulin and other hormones to regulate glucose homeostasis. Even though insulin-secreting beta-cells replicate at very low rates, islet mass can normally slowly expand and adapt to increased insulin requirements. These adaptive mechanisms fail in type 2 diabetes, resulting in insufficient insulin secretion and inadequate beta-cell growth. Although little is known about the molecular regulation of adult beta-cell growth and survival, our recent work illustrates that adult beta-cell replication is tightly regulated by changes in D-type cyclin/cyclin dependent kinase (cdk)-4 activity. However, the upstream and downstream components of these pathways remain very poorly characterized in islets.

What signaling pathways influence beta-cell replication? How does beta-cell failure occur in type 2 diabetes? Where do adult beta- cells come from? Do beta-cells replicate? These are the questions we study using genetic manipulation in mice, along with a variety of in vitro techniques.

New work by our lab with BrdU labeling reveals that adult beta-cells are very long lived, with little evidence for beta-cell turnover in mature animals. Based on this new understanding of the normal life cycle of ß-cells, we feel that much remains to be learned in order to regenerate adult ß-cells. Why do ß-cells proliferate so infrequently? Which ß-cells proliferate? To be honest, we have no idea. However, these questions suggest experimental avenues which we are actively pursuing with rigorous hypothesis-driven studies.

RECENT PUBLICATIONS

Teta M, Rankin MM, Long SY, Stein GM, Kushner JA (2007). Growth and regeneration of adult beta cells does not involve specialized progenitors. Developmental Cell 12(5):817-26

Kushner JA (2006). Beta-Cell Growth: An Unusual Paradigm of Organogenesis That is Cyclin D2/Cdk4 Dependent. Cell Cycle. (3):234-7

Kushner JA, Simpson L, Wartschow LM, Guo S, Rankin MM, Parsons R, and WhiteMF (2005). Phosphatase and tensin homolog regulation of islet growth and glucose homeostasis. Journal of Biological Chemistry, 280 (47): 39388-93

Teta M, Long SY, Wartschow LM, Rankin MM, Kushner JA (2005). Very slow turnover of beta-cells in aged adult mice. Diabetes, 54(8)

Kushner JA, Ciemerych MA, Sicinska E, Wartschow LM, Teta M, Long SY, Sicinski P, White MF (2005). Cyclins D2 And D1 Are Essential for Postnatal Pancreatic Beta-Cell Growth. Molecular and Cellular Biology, 25(9436): 3752-3762

Lab

ROTATION PROJECTS FOR 2006-2007

Please contact Dr Kushner to discuss rotation projects in person.

Lab personnel:

Di Zhou, Undergraduate Research Fellow
Simon Long, Vet School Doctoral Student
Matthew Rankin, Research Technician
Lu Me He, Research Technician
Geneva Stein, Research Technician