Chien Li

Education

  • BS, Tunghai University
  • MS, University of Wisconsin-Milwaukee
  • PhD, University of Pittsburgh
  • PhD, Oregon Health Sciences University

Primary Appointment

  • Associate Professor, Pharmacology

Contact

Research Interest(s)

Neuroendocrine regulation of energy balance and stress, regulation of pancreatic islet hormone secretion and glucose homeostasis

Research Description

The ability to cope with stress is an essential survival mechanism in animals. My laboratory is interested in understanding the effects of stress on energy homeostasis and the implications in the development of metabolic-endocrine disorders such as obesity and type II diabetes. Corticotropin-releasing factor (CRF) family peptides and their receptors (CRFR1 and CRFR2) are key mediators of stress response and we are focusing on their role in the brain and peripheral tissues in regulating appetite and glucose homeostasis. We employ transgenic mice combined with viral gene delivery to elucidate the neurocricuits of CRF family in the brain and use conditional, neuron-specific gene targeting methods to determine the functional importance of the neurocircuits in controlling feeding and body weight. In addition to the central nervous system, CRF peptides play an important role in regulating insulin secretion from pancreatic b cells and insulin function in skeletal muscle cells. We use a number of gene targeting approaches including BAC transgenesis, cell type specific knockouts, and in vitro islet culture to explore the functional role of CRF peptides in modulating glucose homeostasis.

At the molecular level, we are investigating signaling mechanisms and molecular targets in cells mediating the effects of CRF peptides. Currently we have been focusing on vesicular nucleotide transporter (VNUT) as a downstream molecular mediator underlying the effects of stress peptides. Our study has suggested that VNUT plays an essential role in maintaining cellular energy homeostasis. We employ multiple approaches including gene targeting, viral gene delivery, RNA interference and primary tissue culture to determine the functional role of VNUT in regulating energy balance in cells. These studies will contribute to understanding the underlying mechanisms of stress on energy balance and have implications in the management of eating disorders, obesity and diabetes.

We are always looking for talented, highly motivated and productive undergraduate students, potential graduate students, and postdoctoral fellows. Please email CV and inquires about currently available positions.

Selected Publications

  • Chen P, Lin D, Giesler J, Li C. Identification of urocortin 3 afferent projection to the ventromedial nucleus of the hypothalamus in rat brain. The Journal of comparative neurology. 2011;519(10): 2023-42. PMID: 21452217 | PMCID: PMC3694597
  • Chen P, Vaughan J, Donaldson C, Vale W, Li C. Injection of Urocortin 3 into the ventromedial hypothalamus modulates feeding, blood glucose levels, and hypothalamic POMC gene expression but not the HPA axis. American journal of physiology. Endocrinology and metabolism. 2009;298(2): E337-45. PMID: 19952342 | PMCID: PMC2822480
  • Li C, Chen P, Vaughan J, Lee K, Vale W. Urocortin 3 regulates glucose-stimulated insulin secretion and energy homeostasis. Proceedings of the National Academy of Sciences of the United States of America. 2007;104(10): 4206-11. PMID: 17360501 | PMCID: PMC1820733
  • Chen A, Brar B, Choi C, Rousso D, Vaughan J, Kuperman Y, Kim S, Donaldson C, Smith S, Jamieson P, Li C, Nagy T, Shulman G, Lee K, Vale W. Urocortin 2 modulates glucose utilization and insulin sensitivity in skeletal muscle. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(44): 16580-5. PMID: 17050686 | PMCID: PMC1637624
  • Jamieson P, Li C, Kukura C, Vaughan J, Vale W. Urocortin 3 modulates the neuroendocrine stress response and is regulated in rat amygdala and hypothalamus by stress and glucocorticoids. Endocrinology. 2006;147(10): 4578-88. PMID: 16809443
  • Chen A, Perrin M, Brar B, Li C, Jamieson P, Digruccio M, Lewis K, Vale W. Mouse corticotropin-releasing factor receptor type 2alpha gene: isolation, distribution, pharmacological characterization and regulation by stress and glucocorticoids. Molecular endocrinology (Baltimore, Md.). 2004;19(2): 441-58. PMID: 15514029
  • Li C, Chen P, Vaughan J, Blount A, Chen A, Jamieson P, Rivier J, Smith M, Vale W. Urocortin III is expressed in pancreatic beta-cells and stimulates insulin and glucagon secretion. Endocrinology. 2003;144(7): 3216-24. PMID: 12810578
  • Li C, Vaughan J, Sawchenko P, Vale W. Urocortin III-immunoreactive projections in rat brain: partial overlap with sites of type 2 corticotrophin-releasing factor receptor expression. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2002;22(3): 991-1001. PMID: 11826127
  • Vetter D, Li C, Zhao L, Contarino A, Liberman M, Smith G, Marchuk Y, Koob G, Heinemann S, Vale W, Lee K. Urocortin-deficient mice show hearing impairment and increased anxiety-like behavior. Nature genetics. 2002;31(4): 363-9. PMID: 12091910
  • Lewis K, Li C, Perrin M, Blount A, Kunitake K, Donaldson C, Vaughan J, Reyes T, Gulyas J, Fischer W, Bilezikjian L, Rivier J, Sawchenko P, Vale W. Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor. Proceedings of the National Academy of Sciences of the United States of America. 2001;98(13): 7570-5. PMID: 11416224 | PMCID: PMC34709
  • Haskell-Luevano C, Chen P, Li C, Chang K, Smith M, Cameron J, Cone R. Characterization of the neuroanatomical distribution of agouti-related protein immunoreactivity in the rhesus monkey and the rat. Endocrinology. 1999;140(3): 1408-15. PMID: 10067869
  • Li C, Chen P, Smith M. Neuropeptide Y and tuberoinfundibular dopamine activities are altered during lactation: role of prolactin. Endocrinology. 1999;140(1): 118-23. PMID: 9886815
  • Li C, Chen P, Smith M. Neuropeptide Y (NPY) neurons in the arcuate nucleus (ARH) and dorsomedial nucleus (DMH), areas activated during lactation, project to the paraventricular nucleus of the hypothalamus (PVH). Regulatory peptides. 1998;75 93-100. PMID: 9802398
  • Li C, Chen P, Smith M. The acute suckling stimulus induces expression of neuropeptide Y (NPY) in cells in the dorsomedial hypothalamus and increases NPY expression in the arcuate nucleus. Endocrinology. 1998;139(4): 1645-52. PMID: 9528945