Research in my laboratory is focusing on understanding the cellular mechanisms and neuronal pathways controlling glucose and energy homeostasis. Type 2 diabetes mellitus (T2DM) is a metabolic condition displaying chronic hyperglycemia, hyperinsulinemia and hypertriglyceridemia. The incidence of T2DM is rising at an alarming rate with 350 million people expected to develop this pathological condition within the next 20 years. Despite intense research, the primary causes of T2DM are still largely unknown. We suspect that T2DM subjects are heterogeneous in respect to primary dysfunctions. A working hypothesis in the laboratory is that defects in neuronal metabolic-sensing mechanisms may play an important, primary pathogenic role in the development of T2DM. Obesity is also affecting millions of people and treatments 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 hypothalamic and caudal brainstem neurons exert a critical role in controlling energy balance. To test our hypotheses we combine studies on hypothalamic organotypic slice cultures, electrophysiological assays and physiological studies of genetically-engineered mice with neuron-specific mutations.
Ramadori G, Lee CE, Bookout AL, Lee S, Williams KW, Anderson J, Elmquist JK, Coppari R, "Brain SIRT1: Anatomical distribution and regulation by energy availability" Journal of Neuroscience, 28/40:9989-9996, October 2008
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
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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