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| Qualifications |
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2000 Ph.D. Physiology and Biophysics, Weill Graduate School of Medical Sciences, Cornell University, New York, NY.
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| Memberships |
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Society for Neuroscience, Association for Women in Science (AWIS) |
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| Clinical Interests |
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| Obesity, diabetes |
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| Research Interests |
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| 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 initial 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 areas of research interest: (1) The contribution of PTP1B specifically in leptin receptor (LepR)-expressing neurons to the leanness and increased energy expenditure phenotypes of PTP1B-/- mice. (2) How PTP1B deletion in hypothalamic POMC and NPY neurons, as well as in VMH neurons, affects the electrophysiological properties of these neurons in response to insulin and leptin. (3) How CNS-specific deletion of PTP1B affects peripheral adipokine secretion and adipose-specific gene transcription. (4) Developing new genetic mouse models to study tyrosine phosphatase control of metabolism. |
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| Selected Publications |
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| K.K. Bence, M. Delibegovic, B. Xue, C. Gorgun, G. Hotamisligil, B.G. Neel, and B.B. Kahn. Neuronal PTP1B Regulates Body Mass/Adiposity and Leptin Action. Nature Medicine, in press, 2006.
J.M. Zabolotny*, K.K. Bence-Hanulec*, A. Stricker-Krongrad, F. Haj, Y. Wang, Y. Minokoshi, Y.-B. Kim, J.K. Elmquist, L.A. Tartaglia, B.B. Kahn and B.G. Neel. PTP1B Regulates Leptin Signal Transduction In Vivo. Developmental Cell 2, 489-495 (2002). * indicates co-first authors K.K. Bence -Hanulec , J. Marshall, and L.A.C. Blair. Potentiation of Neuronal L Calcium Channels by IGF-1 Requires Phosphorylation of the a 1 Subunit on a Specific Tyrosine Residue. Neuron 27, 121-131 (2000). L.A.C. Blair*, K.K. Bence-Hanulec*, S. Mehta, T. Franke, D. Kaplan, and J. Marshall. Akt-dependent potentiation of L channels by insulin-like growth factor-1 is required for neuronal survival. The Journal of Neuroscience 19(6), 1940-1951 (1999). * indicates co-first authors 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). L.A.C. Blair, K.K. Bence, and J. Marshall. Jellyfish Green Fluorescent Protein: a tool for studying ion channels and second-messenger signaling in neurons. Methods in Enzymology 302, 213-225 (1999). K. Bence , W. Ma, T. Kozasa, and X.-Y. Huang. Direct stimulation of Bruton’s tyrosine kinase by Gq-protein a -subunit. Nature 389, 296-299 (1997). Y. Wan, K. Bence, A. Hata, T. Kurosaki, A. Veillette, and X.-Y. Huang. Genetic evidence for a tyrosine kinase cascade preceding the mitogen-activated protein kinase cascade in vertebrate G-protein signaling. Journal of Biological Chemistry 272 (27), 17209-17215 (1997). J.H. Perlman, A.-O. Colson, W. Wang, K. Bence, R. Osman, and M.C. Gershengorn. Interactions between conserved residues in transmembrane helices 1, 2 and 7 of the thyrotropin-releasing hormone receptor. Journal of Biological Chemistry 272 (18), 11937-11942 (1997). |
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