Research Interests: mouse models of obesity/diabetes, neuronal control of energy balance, signal transduction, role of protein tyrosine phosphatases in obesity and cancer.
Key words: mouse models, obesity, diabetes, signaling, insulin, leptin, phosphatase, cancer, 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 peripheral tissues and how dysregulation of these pathways leads to diseases such as obesity, type II diabetes, and cancer. 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 protein tyrosine phosphatases (PTPs) in specific neuronal populations using conditional mouse models.
(2) Determining how PTPs affect the electrophysiological properties of hypothalamic neurons.
(3) Examining the role of PTPs in linking obesity, insulin resistance, and cancer.
Owen C, Lees E K, Grant L, Zimmer D J, Mody N, Bence K K, Delibegović M: Inducible liver-specific knockdown of protein tyrosine phosphatase 1B improves glucose and lipid homeostasis in adult mice. Diabetologia Jul 2013.
Koss David J, Riedel Gernot, Bence Kendra, Platt Bettina: Store-operated Ca2+ entry in hippocampal neurons: Regulation by protein tyrosine phosphatase PTP1B. Cell calcium 53(2): 125-38, Feb 2013.
Carbone Christopher J, Zheng Hui, Bhattacharya Sabyasachi, Lewis John R, Reiter Alexander M, Henthorn Paula, Zhang Zhong-Yin, Baker Darren P, Ukkiramapandian Radha, Bence Kendra K, Fuchs Serge Y: Protein tyrosine phosphatase 1B is a key regulator of IFNAR1 endocytosis and a target for antiviral therapies. Proceedings of the National Academy of Sciences of the United States of America 109(47): 19226-31, Nov 2012.
De Jonghe Bart C, Hayes Matthew R, Zimmer Derek J, Kanoski Scott E, Grill Harvey J, Bence Kendra K: Food intake reductions and increases in energetic responses by hindbrain leptin and melanotan II are enhanced in mice with POMC-specific PTP1B deficiency. American journal of physiology. Endocrinology and metabolism 303(5): E644-51, Sep 2012.
Tsou Ryan C, Zimmer Derek J, De Jonghe Bart C, Bence Kendra K: Deficiency of PTP1B in Leptin Receptor-Expressing Neurons Leads to Decreased Body Weight and Adiposity in Mice. Endocrinology 153(9): 4227-37, Sep 2012.
Kanoski Scott E, Zhao Shiru, Guarnieri Douglas J, Dileone Ralph J, Yan Jianqun, De Jonghe Bart C, Bence Kendra K, Hayes Matthew R, Grill Harvey J: Endogenous leptin receptor signaling in the medial nucleus tractus solitarius affects meal size and potentiates intestinal satiation signals. American journal of physiology. Endocrinology and metabolism 303(4): E496-503, Aug 2012.
Tsou Ryan C, Bence Kendra K: Central regulation of metabolism by protein tyrosine phosphatases. Frontiers in neuroscience 6: 192, 2012.
Owen Carl, Czopek Alicja, Agouni Abdelali, Grant Louise, Judson Robert, Lees Emma K, Mcilroy George D, Göransson Olga, Welch Andy, Bence Kendra K, Kahn Barbara B, Neel Benjamin G, Mody Nimesh, Delibegović Mirela: Adipocyte-specific protein tyrosine phosphatase 1B deletion increases lipogenesis, adipocyte cell size and is a minor regulator of glucose homeostasis. PloS one 7(2): e32700, 2012.
Fuentes Federico, Zimmer Derek, Atienza Marybless, Schottenfeld Jamie, Penkala Ian, Bale Tracy, Bence Kendra K, Arregui Carlos O: Protein Tyrosine Phosphatase PTP1B Is Involved in Hippocampal Synapse Formation and Learning. PloS one 7(7): e41536, 2012.
Tsou Ryan C, Bence Kendra K: The Genetics of PTPN1 and Obesity: Insights from Mouse Models of Tissue-Specific PTP1B Deficiency. Journal of obesity 2012: 926857, 2012.
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Last updated: 10/02/2013
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