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Assistant Professor of Pharmacology
Primary Office: 2-532 Bowen Science BuildingIowa City, IA 52242
Primary Office Phone: 319-384-4729
Lab: 2-551 Bowen Science BuildingIowa City, IA 52242
BS, Biological Sciences, Nanjing University (China)PhD, Cellular Biology, University of Georgia
Post Doctoral, HHMI and Department of Biochemistry, University of Washington, Seattle, WA
Biosciences Graduate ProgramInterdisciplinary Graduate Program in GeneticsInterdisciplinary Graduate Program in Neuroscience
Our lab is studying neural control of feeding behavior and etiology of eating-associated disorders, such as obesity and anorexia nervosa, in genetic mouse models. Ready access to the palatable and calorie-dense foods is considered to be one of the causal factors of the high prevalence of obesity in industrialized countries. In contrast, anorexia nervosa, an eating disorder characterized by uncontrolled dieting and purging behaviors, often leads to rapid and dramatic weight loss, which can be life-threatening in some cases. When provided with unlimited calories, why does the food consumption vary so much in the population such that some become obese, some underweight, while others still stay lean? Feeding behavior is tightly regulated at several levels in the central nervous system. Peripheral hormonal and nutritional signals impinge onto several hypothalamic and brainstem nuclei to regulate appetite and energy metabolism in a largely subconscious manner. Meanwhile, higher cognitive centers also modulate food intake. A challenging question is how neural circuits that underlie the basic drive to feed interact with those representing conscious wish to mediate feeding-related activities.
Hypothalamic AgRP neurons are critical for regulation of feeding and body weight, as acute ablation of these cells in adult mice leads to anorexia and profound weight loss (see Review Article: Wu & Palmiter, Eur. J. Pharmacol., 2011). We demonstrated that such anorexic phenotype is fully reversible with the aid of a GABA-A receptor agonist and that GABA release from AgRP neurons onto neurons in the lateral parabrachial nucleus (PBN) is essential for maintenance of appetite and body weight ( Wu et al., Cell, 2009). Therefore, we proposed that a novel hindbrain circuit and associated signaling pathways underlie neural adaptive control of anorexia and obesity through bi-directional modulation.
1. Characterize functional connectivity of metabolic-sensing PBN neurons and their roles in control of feeding and energy homeostasis. We would expect to reveal the anatomical and functional organization of the PBN and how it interacts with other brain regions to promote compensatory adaptation after ablation of AgRP neurons. Moreover, we would expect to establish precise physiological roles and pivotal signaling mechanisms of distinct subpopulations of the PBN neurons in control of appetite and body weight.
2. Identify a hindbrain neural circuit and associated signaling pathways that mediate feeding and addictive response to food in transgenic mouse models. Our preliminary results indicated that a hindbrain neural circuit might be functionally organized by several critical signaling pathways that integrate metabolic inputs from the hypothalamus along with gustatory and vagal stimuli to promote long-term adaptation to different homeostatic level. The potential outcome will illuminate a more complete feeding circuitry in the mammalian brain and novel adaptive mechanisms at synapse level that might contribute to developing therapeutic approaches against obesity and eating disorders.
Deciphering a neuronal circuit that mediates appetite.
2012 March 14. 483(7391):594-597.
Ablation of neurons expressing agouti-related protein, but not melanin concentrating hormone, in leptin-deficient mice restores metabolic functions and fertility.
Proc Natl Acad Sci USA.
2012 February 21. 109(8):3155-3160.
GABAergic signaling by AgRP neurons prevents anorexia via a melanocortin-independent mechanism.
Eur J Pharmacol.
2011 June 11. 660(1):21-7.
Loss of GABAergic signaling by AgRP neurons to the parabrachial nucleus leads to starvation.
2009 June 26. 137(7):1225-1234.
Ablation of neurons expressing agouti-related protein activates fos and gliosis in postsynaptic target regions.
2008 September 10. 28(37):9218-9226.
Starvation after AgRP neuron ablation is independent of melanocortin signaling.
Proc Natl Acad Sci U S A.
2008 February 19. 105(7):2687-2692.
Date Last Modified: 07/31/2013 -
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