Yuling Chi, Ph.D.
The focuses of our scientific research have been development of chemical tools and potential pharmacological agents, application of those tools to characterize biological functions of specific genes and proteins, and evaluation of those agents as potential therapeutics targeting pathological conditions.
Previously we took an approach of high throughput screening and subsequent structure-relation studies of synthetic small molecules to develop inhibitors of specific genes using cell based assays. We have successfully developed potent inhibitors of prostaglandin transporter (PGT). Prostaglandins (PGs) are found in virtually all tissues and organs. They are autocrine and paracrine lipid mediators that act upon platelet, endothelium, uterine and mast cells, and diverse immune cells. The biological signals and physiological events they trigger range from pain and inflammation, to vasodilation and urinary sodium excretion, to cell growth and angiogenesis, and to thermogenesis and adipogenesis. PGT regulates the degradation and metabolism of PGs and thereby regulates PG signaling. We have demonstrated that PGT regulates angiogenesis in wound healing. Inhibition of PGT accelerates wound healing in diabetes. We are currently investigating the role of PGT in inflammation during wound healing. We will further elucidate the molecular mechanisms by which PGT modulates inflammation and angiogenesis in wound healing.
Recently we have started another major project, evaluation of natural compounds in modulation of metabolic syndromes including obesity and diabetes, and investigation of the molecular and cellular mechanisms by which those natural compounds improve those pathological conditions. We have identified magiferin that can protect against diet induced metabolic disorders. Our unbiased proteomics study revealed that mangiferin upregulates mitochondrial bioenergetics and downregualtes lipogenesis. Furthermore, we found that mangiferin is a novel activator of pyruvate dehydrogenase (PDH), which is the central gate-keeper of carbohydrate oxidative metabolism. We are currently investigating the molecular mechanisms of mangiferin modulation of mitochondrial bioengetics, lipogenesis and adipogenesis. We are also studying the pharmacokinetics and pharmacodynamics of mangifering, and developing mangiferin into a therapeutics for treatment of metabolic disorders.
Selected Recent Publications
- Yuling Chi, Bo Zhou, Wei-Qing Wang, Sung-Kee Chung, Yong-Uk Kwon, Young-Hoon Ahn, Young-Tae Chang, Yosuke Tsujishita, James H. Hurley and Zhong-Yin Zhang: Comparative Mechanistic and Substrate Specificity Study of Inositol Polyphosphate 5-Phosphatase Schizosaccharomyces Pombe Synaptojanin and SHIP2. J Biol Chem. 279: 44987-95, 2004.
- Yuling Chi, Sonya M. Khersonsky, Young-Tae Chang and Victor L. Schuster:Identification of a New Class of PGT Inhibitors and Characterization of Their Biological Effects on PGE2 Transport. J Pharmacol Exp Ther. 316:1346-50, 2006.
- Yuling Chi, Pucci ML and Victor L. Schuster: Dietary salt induces transcription of the prostaglandin transporter gene in renal collecting ducts. Am J Physiol Renal Physiol. 295: F765-7, 2008.
- Yuling Chi and Victor L. Schuster: The Prostaglandin Transporter PGT Transports PGH2. BBRC. 395: 168-72, 2010.
- Yuling Chi, Jaeki Min, Jean-Francois Jasmin, Michael Lisanti, Young-Tae Chang, Victor L. Schuster: Development of High Affinity Inhibitor of Prostaglandin Transporter PGT. J Pharmacol Exp Ther. 339: 633-41, 2011.
- Hao Qian, Na Luo, and Yuling Chi: Aging-Shifted Prostaglandin Profile in Endothelium as a Factor in Cardiovascular Disorders. J Aging Res. Vol. 2012, 2012.
- George Han, Long N. Nguyen Chitralekha Macherla, Yuling Chi, Joel M. Friedman, Joshua D. Nosanchuk, and Luis R. Martinez: Nitric oxide-releasing nanoparticles accelerate wound healing by promoting fibroblast migration and collagen deposition. Am J Pathol. 180 : 1465-73, 2012.
- Mahrukh M. Syeda, Xiaohong Jing, Raihan H. Mirza, Hong Yu, Rani S. Sellers, and Yuling Chi: Prostaglandin Transporter Modulates Wound Healing in Diabetes by Regulation of Prostaglandin-Induced Angiogenesis. Am J Pathol. 181: 334-46, 2012.
- Raihan H. Mirza, Nan Chi, Yuling Chi Therapeutic Potential of the Natural Product Mangiferin in Metabolic Syndrome. J Nutr Ther. 2: 74-79, 2013.
- Yuling Chi and Anthony A. Sauve: Nicotinamide riboside, a trace nutrient in foods, is a Vitamin B3 with effects on energy metabolism and neuroprotection. Curr Opin Clin Nutr Metab Care. 16: 657-661, 2013.
- Jihyeon Lim, Zhongbo Liu, Pasha Apontes, Daorong Feng, Jeffrey E. Pessin, Anthony A. Sauve,Ruth H. Angelettiand Yuling Chi:Dual Mode Action of Mangiferin in Mouse Liver under High Fat Diet. PLoS One 9: e90137, 2014.
- Pasha Apontes, Zhongbo Liu, Kai Su, Outhiriaradjou Benard, Dou Y. Youn, Xisong Li, Wei Li, Raihan H. Mirza, Claire C. Bastie, Linda A. Jelicks, Jeffrey E. Pessin, Radhika H. Muzumdar, Anthony A. Sauve, and Yuling Chi: Mangiferin Stimulates Carbohydrate Oxidation and Protects against High Fat Diet Induced Metabolic Disorders. Diabetes 2014 (in press).
- Yuling Chi, Sylvia O. Suadicani & Victor L. Schuster: Regulation of Prostaglandin EP1 and EP4 Receptor Signaling by Carrier-Mediated Ligand Reuptake. Pharmacol Res Perspect. 2014 (in press).
- Zhongbo Liu, Pasha Apontes, Mahrukh M. Syeda, Raihan H. Mirzaand Yuling Chi: Inhibition of Prostaglandin Transporter Accelerates Wound Healing in Diabetic Rats by Promoting Perfusion and Vascularization. (In preparation)
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Dr. Yuling Chi
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