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.