Jake Alden Kushner

Assistant Professor of Pediatrics

Department: Pediatrics

Contact information

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

Office: 267-426-5717
Fax: 215-590-1605

Email:
kushnerj@mail.med.upenn.edu

Graduate Group Affiliations

Cell and Molecular Biology

Publications

Search PubMed for articles

Links
Search PubMed for articles
Cell and Molecular Biology graduate group faculty webpage.

Education
B.A. (Biochemistry)
University of California at Berkeley, 1987.
M.D.
Albany Medical College, 1994.

Permanent link

Description of Research Expertise

Research Interests
molecular regulation of cell cycle, adult beta- cell replication.

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

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.

Rotation Projects for 2006-2007
Please contact Dr Kushner to discuss rotation projects in person.

Lab personnel:
Swaroop Bommareddi, Undergraduate Research Fellow
Simon Long, Vet School Doctoral Student
Matthew Rankin, Research Technician
Jasmine Smith, Rotation Student
Monica Teta, Research Technician
Lashon Ussin, Rotation Student
Allison Zajac, Research Technician

Description of Clinical Expertise

Care of children with diabetes mellitus and other endocrine disorders.

Selected Publications

Kushner JA: Beta-cell growth: an unusual paradigm of organogenesis that is cyclin D2/Cdk4 dependent. Cell Cycle 5(3), February 2006.

Kushner JA, Ciemerych MA, Sicinska E, Wartschow LM, Teta M, Long SY, Sicinski P, White MF: Cyclins D2 and D1 are essential for postnatal pancreatic beta-cell growth. Molecular and Cellular Biology 25(9436): 3752-3762, May 2005.

Yi X, Schubert M, Peachey NS, Suzuma K, Burks DS, Kushner JA, Suzuma I, Cahill C, Flint CL, Dow MA, Leshan RL, King GL, White MF: Insulin receptor substrate 2 is essential for maturation and survival of photoreceptor cells. The Journal of Neuroscience 25(7), February 2005.

Teta M, Long SY, Wartschow LM, Rankin MM, Kushner JA : Very slow turnover of beta-cells in aged adult mice. Diabetes 54(9): 2557-67, September 2005.

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

Kushner JA, Haj HG, Klaman LD, Dow MA, Kahn BB, Neel BG, and White MF: Islet-sparing effects of protein tyrosine phosphatase-1b deficiency delays onset of diabetes in IRS2 knockout mice. Diabetes 53(1): 61-66, January 2004.

Pawlak DB, Kushner JA, Ludwig DS : Effects of dietary glycemic index on adiposity, glucose homeostasis and plasma lipids in an animal model. The Lancet 364(9436): 778-85, August 2004.

Kushner JA, Ciemerych MA, Sicinska E, Sicinsk P, White MF: D-Type cyclins are essential for normal cell cycle regulation of islet growth. Keystone Symposium. Diabetes Mellitus: Molecular Signaling, Genes and Therapeutics. Banff, Alberta Canada. Page: 99. Poster 248, March 4-20 2004.

Kushner JA, Simpson L, Wartschow LM, Parsons R, White MF: PTEN Regulation of Glucose Homeostasis and Islet Growth. The American Diabetes Association 64st Scientific Session. Orlando, FL. Diabetes 53(supp 2): A51, Poster 219-OR, June 2004.

Lin X, Taguchi A, Park S, Kushner JA, Li F, Li Y, White MF: Dysregulation of insulin receptor substrate 2 in beta-cells and brain causes obesity and diabetes. The Journal of Clinical Investigation 114(7): 908-916, October 2004.

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