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.
Selected Publications
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: The Genetics of PTPN1 and Obesity: Insights from Mouse Models of Tissue-Specific PTP1B Deficiency. Journal of obesity 2012: 926857, 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.
Loh Kim, Fukushima Atsushi, Zhang Xinmei, Galic Sandra, Briggs Dana, Enriori Pablo J, Simonds Stephanie, Wiede Florian, Reichenbach Alexander, Hauser Christine, Sims Natalie A, Bence Kendra K, Zhang Sheng, Zhang Zhong-Yin, Kahn Barbara B, Neel Benjamin G, Andrews Zane B, Cowley Michael A, Tiganis Tony: Elevated hypothalamic TCPTP in obesity contributes to cellular leptin resistance. Cell metabolism 14(5): 684-99, Nov 2011.
Balavenkatraman Kamal K, Aceto Nicola, Britschgi Adrian, Mueller Urs, Bence Kendra K, Neel Benjamin G, Bentires-Alj Mohamed: Epithelial protein-tyrosine phosphatase 1B contributes to the induction of mammary tumors by HER2/Neu but is not essential for tumor maintenance. Molecular cancer research : MCR 9(10): 1377-84, Oct 2011.
Agouni Abdelali, Mody Nimesh, Owen Carl, Czopek Alicja, Zimmer Derek, Bentires-Alj Mohamed, Bence Kendra K, Delibegović Mirela: Liver-specific deletion of protein tyrosine phosphatase (PTP) 1B improves obesity- and pharmacologically induced endoplasmic reticulum stress. The Biochemical journal 438(2): 369-78, Sep 2011.
De Jonghe Bart C, Hayes Matthew R, Bence Kendra K: Melanocortin control of energy balance: evidence from rodent models. Cellular and molecular life sciences : CMLS 68(15): 2569-88, Aug 2011.
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Last updated: 10/03/2012
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