Yuling Chi, Ph.D.
The focuses of our scientific research have been studying the molecular and cellular mechanisms of metabolic disorders including obesity and diabetes, diabetic complications, such as impaired wound healing, and developing pharmacological and nutraceutical therapeutics.
We have developed and established experimental settings and methodologies to study mitochondrial functions, fuel (such as glucose and fatty acid) selection and utilization in cells, tissues and whole body, and to study metabolically important physiological/pathological aspects of animals including glucose homeostasis, insulin sensitivity, energy homeostasis, and etc.
We have discovered that a natural compound, mangiferin (MGF), is a novel activator of pyruvate dehydrogenase (PDH), which is the central gate-keeper of carbohydrate oxidative metabolism in mitochondria. MGF enhances carbohydrate oxidation in myotubes and muscle tissues. Our unbiased proteomics study revealed that MGF upregulates mitochondrial bioenergetics and downregualtes lipogenesis. We are currently investigating the molecular mechanisms of mangiferin modulation of mitochondrial bioenergetics, lipogenesis, lipolysis and adipogenesis. We are also studying the pharmacokinetics and pharmacodynamics of MGF, and developing MGF into a therapeutics for treatment of metabolic disorders.
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. We have shown that PGT regulates the degradation and catabolism of PGs and thereby regulates PG signaling.
Taking an approach of high throughput screening and subsequent structure-relation studies of synthetic small molecules we have successfully developed potent inhibitors of prostaglandin transporter (PGT).
We have uncovered that prostaglandin transporter (PGT) plays an important role in wound healing, especially diabetic wound healing. 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.
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, Michael L. Pucci 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 and 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 and 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. Angeletti and 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 63: 3626-36, 2014.
- Yuling Chi, Sylvia O. Suadicani and Victor L. Schuster: Regulation of Prostaglandin EP1 and EP4 Receptor Signaling by Carrier-Mediated Ligand Reuptake. Pharmacol Res Perspect. 2: e00051, 2014.
- Outhiriaradjou Benard and Yuling Chi: Medicinal Properties of Mangiferin, Structural Features, Derivative Synthesis, Pharmacokinetics and Biological Activities. Mini Rev Med chem. 15: 582-94, 2015.
- Yuling Chi, Jean-Francois Jasmin, Yoshinori Seki, Michael P. Lisanti, Maureen J. Charron, David J. Lefer and Victor L. Schuster: Inhibition of the prostaglandin transporter PGT lowers blood pressure in hypertensive rats and mice. PLoS ONE 2015 (in press).
- Outhiriaradjou Benard, Jihyeon Lim, Pasha Apontes, Ruth H. Angeletti and Yuling Chi: Impact of High Fat Diet on The Proteome of Mouse Liver. 2015 (in review).
- Zhongbo Liu, Pasha Apontes, Mahrukh M. Syeda, Raihan H. Mirza and Yuling Chi: Inhibition of Prostaglandin Transporter (PGT) Promotes Perfusion and Vascularization and Accelerates Wound Healing in Non-diabetic and Diabetic Rats. 2015 (In review).
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Dr. Yuling Chi
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