Kendra K Bence

Contact information

3800 Spruce Street
Vet 223E
Philadelphia, PA 19104

Office: 215-746-2998
Fax: 215-573-5186

Graduate Group Affiliations

Education:
B.A. (Department of Biology)
Colgate University, Hamilton, NY, 1993.
Ph.D. (Physiology, Biophysics, and Molecular Medicine)
Cornell University Weill Graduate School of Medical Sciences, New York, N.Y. Conducted thesis research in abstentia. Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI., 2000.

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Description of Research Expertise

Research Interests: mouse models of obesity/diabetes, neuronal control of energy balance, signal transduction.

Key words: mouse models, obesity, diabetes, signaling, insulin, leptin, phosphatase, neuroscience, hypothalamus.

The research interests of my laboratory focus on the role of tyrosine phosphorylation and dephosphorylation in cell signaling and disease. In particular, we study how protein-tyrosine phosphatases (PTPs) regulate signaling pathways in the brain and how dysregulation of these pathways leads to diseases such as obesity and type II diabetes. Understanding the pathways regulating metabolic processes is of critical importance because these diseases are reaching epidemic proportions. Many of these pathways involve tyrosyl phosphorylation, and although it is clear that tyrosine phosphorylation plays an important role in CNS control of body mass, the identity of specific PTPs involved in these signaling events remain largely unknown. Leptin, an adipocyte secreted hormone, acts on specific hypothalamic nuclei to initiate a tyrosine signaling cascade through the leptin receptor-associated Janus kinase 2 (Jak2). Mutations in either leptin (ob/ob) or its receptor (db/db) result in severe obesity in mice and humans, demonstrating the importance of leptin signaling in control of body mass. Protein-tyrosine phosphatase-1B (PTP1B) is a negative regulator of leptin signaling through inhibition of Jak2, and mice lacking this gene are lean and have increased energy expenditure. In studies using inducible mouse models of PTP1B, we found the brain to be the critical site of action for PTP1B regulation of body mass.

Current research focus:

(1) Studying the metabolic role of the tyrosine phosphatases PTP1B and SHP2 in specific neuronal populations using conditional mouse models.

(2) Determining how PTP1B or SHP2 deletion in hypothalamic neurons affect the electrophysiological properties of these neurons.

(3) Profiling expression of PTP genes in obesity and diabetes.

(4) Developing new genetic mouse models to study tyrosine phosphatase control of metabolism.

Selected Publications

Xue B, Pulinilkunnil T, Murano I, Bence KK, He H, Minokoshi Y, Asakura K, Lee A, Haj F, Furukawa N, Catalano KJ, Delibegovic M, Balschi JA, Cinti S, Neel BG, Kahn BB. : Neuronal protein tyrosine phosphatase 1B deficiency results in inhibition of hypothalamic AMPK and isoform-specific activation of AMPK in peripheral tissues. Mol Cell Biol 29(16): 4563-73, Aug 2009 Notes: PMID: 19528236

M. Delibegovic, D. Zimmer, C. Kauffman, K. Rak, E.-G. Hong, Y.-R. Cho, J. K. Kim, B. B. Kahn, B. G. Neel, and K. K. Bence: Liver-Specific Deletion of Protein-Tyrosine Phosphatase 1B (PTP1B) Improves Metabolic Syndrome and Attenuates Diet-Induced ER Stress. Diabetes 58(3): 590-9, Mar 2009 Notes: PMID: 19074988

Hayes MR, Skibicka KP, Bence KK, Grill HJ: Dorsal hindbrain 5'-adenosine monophosphate-activated protein kinase as an intracellular mediator of energy balance. Endocrinology 150(5): 2175-82, May 2009 Notes: PMID: 19116341

Bart C. De Jonghe and Kendra K. Bence: Brown fat – who, what, when, where, why, how? Cell Science Reviews 5(2), October 2008.

Kontaridis MI, Yang W, Bence KK, Cullen D, Wang B, Bodyak N, Ke Q, Hinek A, Kang PM, Liao R, Neel BG.: Deletion of Ptpn11 (Shp2) in cardiomyocytes causes dilated cardiomyopathy via effects on the extracellular signal-regulated kinase/mitogen-activated protein kinase and RhoA signaling pathways. Circulation 117(11): 1423-35, March 2008 Notes: PMID: 18316486

M. Delibegovic, K.K. Bence, N. Mody, E.G. Hong, H.J. Ko, J.K. Kim, B.B. Kahn, and B.G. Neel.: Improved Glucose Homeostasis in Mice with Muscle-specific Deletion of Protein Tyrosine Phosphatase 1B. Molecular and Cellular Biology 27(21): 7727-34, Nov 2007 Notes: PMID: 17724080

L.A.C. Blair, K.K. Bence, J. Marshall.: GFP in the Study of Neuronal Signalling Pathways. Current Protocols in Neuroscience section 5.15 , 2000.

Bence, Kendra K. Delibegovic, Mirela. Xue, Bingzhong. Gorgun, Cem Z. Hotamisligil, Gokhan S. Neel, Benjamin G. Kahn, Barbara B.: Neuronal PTP1B regulates body weight, adiposity and leptin action. Nature Medicine 12(8): 917-24, Aug 2006.

Blair, L A. Bence, K K. Marshall, J.: Jellyfish green fluorescent protein: a tool for studying ion channels and second-messenger signaling in neurons. Methods in Enzymology 302: 213-25, 1999.

Zabolotny, Janice M. Bence-Hanulec, Kendra K. Stricker-Krongrad, Alain. Haj, Fawaz. Wang, Yongping. Minokoshi, Yasuhiko. Kim, Young-Bum. Elmquist, Joel K. Tartaglia, Louis A. Kahn, Barbara B. Neel, Benjamin G.: PTP1B regulates leptin signal transduction in vivo.[see comment]. Developmental Cell 2(4): 489-95, Apr 2002.

Bence-Hanulec, K K. Marshall, J. Blair, L A.: Potentiation of neuronal L calcium channels by IGF-1 requires phosphorylation of the alpha1 subunit on a specific tyrosine residue. Neuron 27(1): 121-31, Jul 2000.

Blair, L A. Bence-Hanulec, K K. Mehta, S. Franke, T. Kaplan, D. Marshall, J.: Akt-dependent potentiation of L channels by insulin-like growth factor-1 is required for neuronal survival. Journal of Neuroscience 19(6): 1940-51, Mar 15 1999.

Bence, K. Ma, W. Kozasa, T. Huang, X Y.: Direct stimulation of Bruton's tyrosine kinase by G(q)-protein alpha-subunit. Nature 389(6648): 296-9, Sep 18 1997.

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