Neurobiology
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Xiaoning Bi, MD, PhD Professor of Physiology COMP-Pomona xbi@westernu.edu Office#: (909) 469-5487 – Lab#: (909) 469-5471 |
Research Interests: Research in my laboratory seeks to understand how neurons develop, mature, and function properly, and how they die when challenged by natural aging process, intrinsic genetic defects, or various insults. We hope that, by understanding the basic molecular and cellular mechanisms that govern these processes, we can develop better preventive and therapeutic strategies for central nervous system disorders in children as well as in elders. Current Research Projects: 1. Signaling pathways in learning and memory and other brain functions. Signal transmission at junctions between neurons, the synapses, is regulated by multiple signaling pathways. One of my lab projects for the last few years has focused on the mTOR (mechanistic/mammalian target of rapamycin) signaling pathway. The mTOR network consists of two complexes mTORC1 and mTORC2 and integrates signals from nutrients, energy levels, growth factors, and stress status. We have recently found that mTORC1 activity is increased while mTORC2 activity is decreased in a mouse model of Angelman syndrome (AS), a disease caused by maternal UBE3A deficiency. Furthermore, the imbalanced mTORC1 and mTORC2 activity is causally related to learning and memory impairment and motor dysfunction in AS mice. These results suggest that mTOR signaling is regulated by UBE3A. Since abnormal mTOR signaling has been reported in other neurological disorders, including Alzheimer’s disease and autism spectrum disorders, our findings may have broad implications. 2. Regulation of potassium channels by UBE3A Small conductance calcium-activated potassium channels (SK1-3) are widely distributed throughout the brain and other organs. SK2 channels play important roles in learning and memory and in abnormal brain functions, such as seizures. We have demonstrated that synaptic SK2 levels are regulated by UBE3A and the lack of this regulation resulting from UBE3A deletion contributes to learning impairment in Angelman syndrome mice. Since SK2 channels are widely expressed in mammalian brain, these findings have significant implications for a vast array of neurologic/neuropsychiatric disorders. |
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Nissar A. Darmani, PhD Associate Dean for Basic Sciences and Research Chair, Basic Medical Sciences COMP-Pomona ndarmani@westernu.edu Office#: (909) 469-5654 – Lab#: (909) 469-5218 |
Research Interests:
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Edward Wagner, PhD Professor of Physiology COMP-Pomona ewagner@westernu.edu Office/Lab#: (909) 469-5239 |
Research Interests: My research interests focus on how cannabinoids regulate the hypothalamic feeding circuitry to affect changes in feeding behavior and energy homeostasis in male and female subjects, and how gonadal steroids modulate this interaction. I use state-of-the-art instrumentation to assess cannabinoid-induced changes in daily and hourly food intake, as well as meal size, frequency and duration, core body temperature and weight gain/loss, and how these changes correlate with alterations in neurotransmitter release and cell excitability at anorexigenic proopiomelanocortin (POMC) synapses within the hypothalamic arcuate nucleus. I recently have discovered that males are much more sensitive to the appetite-modulating properties of CB1 receptor agonists and antagonists than females, which correlates with marked sex differences in the pre- and post synaptic actions of cannabinoids at POMC synapses. These findings indicate that gender should be taken into account when considering the use of cannabinoids in the treatment of HIV/AIDS- or cancer-related cachexia, or obesity. |