Our research is focusing on understanding the cellular mechanisms and neuronal pathways controlling glucose and energy homeostasis. Type 2 diabetes (2DM) is the result of impaired glucose homeostasis leading to chronic hyperglycemia. The incidence of diabetes is rising at an alarming rate with 350 million people worldwide expected to develop this pathological condition within the next 20 years. Despite intense research, the primary causes of 2DM are still largely unknown. We suspect that 2DM subjects are heterogeneous in respect to primary dysfunctions. A working hypothesis in the laboratory is that defects in neuronal glucose-sensing mechanisms may play an important, primary pathogenic role in the development of 2DM. Obesity is also affecting millions of people and treatment to prevent or cure it are urgently needed. In the laboratory, we are currently testing whether metabolic-sensor proteins (i.e.: proteins that link the status of energy availability with cellular gene expression, activity and fate) in central neurons are playing a critical role in controlling energy balance. To test our hypothesis we combine studies on hypothalamic organotypic slice cultures, electrophysiological assays and physiological studies of genetically-engineered mice with neuron-specific mutations.
RESEARCH INTERESTS
Cellular and Molecular Neuroendocrinology
RECENT PUBLICATIONS
Parton LE*, Ye CP*, Coppari R*, Enriori PJ*, Choi B, Zang CY, Xu C, Vianna CR, Balthasar N, Lee CE, Elmquist JK, Cowley MA, Lowell BB, "Glucose-sensing by POMC Neurons Regulates Glucose Homeostasis and is Impaired in Obesity" 2007, Nature:228-232 *=Equally contributing Authors
Lazarus M, Yoshida K, Coppari R, Bass C, Mochizuki T, Lowell BB, Saper CB, "EP3 Prostaglandin Receptors in the Median Preoptic Nucleus are Critical for Fever Responses" 2007, Nature Neuroscience 10:1131-33
McHugh TJ, Jones MW, Quinn JJ, Balthasar N, Coppari R, Elmquist JK, Lowell BB, Fanselow MS, Wilson MA, Tonegawa S, "Dentate Gyrus NMDA Receptors Mediate Rapid Pattern Separation in the Hippocampal Network" 2007, Science 317:94-99
Vianna CR, Huntgeburth M, Coppari R, Choi C, Lin J, Krauss S, Barbatelli G, Tzameli I, Kim YB, Cinti S, Shulman GI, Spiegelman BM, Lowell BB, "Hypomorphic Mutation in PGC1b causes Mitochondrial Dysfunction and Liver Insulin Resistance" 2006, Cell Metabolism 4:453-464
Kievit P, Howard JK, Balthasar N, Coppari R, Mori H, Lee CE, Elmquist JK, Yoshimura A, Flier JS, "Enhanced Leptin Sensitivity and Improved Glucose Homeostasis in Mice lacking Suppressor of Cytokine Signaling-3 in POMC Neurons" 2006, Cell Metabolism 4:123-132
SIGNIFICANT PUBLICATIONS
Parton LE*, Ye CP*, Coppari R*, Enriori PJ*, Choi B, Zang CY, Xu C, Vianna CR, Balthasar N, Lee CE, Elmquist JK, Cowley MA, Lowell BB, "Glucose-sensing by POMC Neurons Regulates Glucose Homeostasis and is Impaired in Obesity" 2007, Nature:228-232 *=Equally Contributing Authors
Coppari R*., Ichinose M*, Lee CE, Pullen AE, Kenny CD, McGovern RA, Tang V, Liu SM, Ludwig T, Chua JSC, Lowell BB, Elmquist JK, "The Hypothalamic Arcuate Nucleus: A Key Site for Mediating Leptin’s Effects on Glucose Homeostasis and Locomotor Activity" 2005, Cell Metabolism 1:63-72 *=Equally Contributing Authors
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