WANG Heyao
Professor/Ph.D candidate supervisor, Principal Investigator
Metabolic Disease Research Center
Personal Homepage
CONTACT
hywang@simm.ac.cn
+86-21-50805785
201203
555 Zu Chong Zhi Road, Zhang Jiang Hi-Tech Park, Pudong, Shanghai, P.R.China
Biography
WANG Heyao was graduated with his PhD degree from Kobe University of Japan. In April 2005, she joined SIMM as Principal Investigator to setup a metabolic endocrine pharmacological research platform and current research interest is focused on the drug discovery and pharmacodynamics/pharmacological studies on metabolism disorders, such as obesity, type 2 diabetes, hyperlipidemia, hyperuricemia and fatty liver disease. In the past years of independent research, she has published more than 80 research articles in SCI journals and applied for 36 Chinese invention patents, in which 24 patents have been authorized.
EDUCATION
1981.09 - 1986.07 Henan Medical University
1990.04 - 1997.03 Kobe University of Japan
WORK EXPERIENCE
1986.09 - 1990.03 Affiliated Hospital of NanYang Medical College
1997.04 - 2003.03 Chiba University of Japan
2003.04 - 2005.03 Research Institute, International Medical Center of Japan
2005.05 - present Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Research Directions
1.The major focus of our lab is drug discovery and pharmacodynamics/pharmacological studies on metabolism disorders, such as obesity, type 2 diabetes, hyperlipidemia, hyperuricemia and fatty liver disease.
2.Using the active compounds and combining with the cell and molecular biology techniques to explore the new mechanisms and identify new drug targets for metabolic diseases.
3.Studies focus on the mechanism of glucolipotoxicity of pancreatic β cells and discovery drug for β cell protection.
4.Studies focus on the function of adipocytes/hepatocytes and discovery compounds for regulating the process.
5.Studies focus on the mechanism of melanin metabolism and discovery compounds for regulating the process.
Grants & Research Projects
1.Chinese Academy of Sciences, Strategic Priority Research Program of “Personalized Medicines—Molecular Signature-based Drug Discovery and Development”, Study on the structure optimization and anti-diabetic effects of novel FABP4/5 inhibitors; Project Leader
2.National Ministry of Science & Technology, Major Project “Key New Drug Creation and Manufacturing Program”; Study on novel DGAT1 inhibitors as lipid-lowering candidates; Project Leader
3.Natural Science Foundation of China; Pharmacological study on procyanidolic oligomer Cinnamtannin D1 in protecting pancreatic β cell via autophagy induction; Project Leader
4.Chinese Academy of Sciences, Institutes for Drug Discovery and Development, Self-deployment research program, Study on novel non-systemic DGAT1 inhibitors as lipid-lowering candidates; Project Leader
5.Chinese Academy of Sciences, Institutes for Drug Discovery and Development, Self-deployment research program, Study on the mechanisms of FABP4 inhibition-mediated improvement of chronic low-grade inflammation and glycolipid metabolism disorders; Project Leader
6.Shanghai Health Committee, the Shanghai Three-year Plan on Promoting TCM Development; combination of Chinese traditional and Western medicine Clinical major project (heart failure) ; Project Leader
7.Natural Science Foundation of China; Study on a novel anti-diabetic target FABP4 and the pharmacological mechanisms of its small molecule inhibitor; Project Leader
8.Shanghai Science and Technology Commission, China; Studies on inhibition of calcium signal to reduce islet β-cell damage caused by fatty acids and its mechanism; Project Leader
9.Natural Science Foundation of China; Study on the mechanism that GPR40 antagonist protects MIN6 β-cells from palmitate-induced dysfunction; Project Leader
10.Shanghai Science and Technology Commission, China; Discovery of inhibitors of BRAF V600E as specific anti-melanoma lead compounds; Project Leader
11.National 863, Ministry of Science and Technology (MOST), China; Study on the signal transduction pathway of long chain fatty acid receptors and discovery of anti-diabetes lead compounds; Project Leader
12.Paticipate in several research project, such as 863 and 973 project of MOST, Special Project for "Major New Drugs Innovation and Development" of MOST, Natural Science Foundation of China, Knowledge Innovation Project of The Chinese Academy of Sciences, and Candidate Drugs Study of SIMM, etc.
Achievements
1.The major focus of our lab is drug discovery and molecular pharmacology study on metabolism disorders, such as obese, T2DM and hyperlipidemia. Established high-throughput assays for screening hypoglycemic drugs, including cell based or cell-free methods. For example, FFA receptors ( GPR40, GPR120, GPR119), DGAT1/2, FABP4/5/3 and pancreatic lipase, Adrenaline receptor family (β2AR、β3AR), Melanocortin Receptor (MC3R, MC4R), melanin-concentrating hormone(MCHR1, MCHR2), and some other drug targets including GLP-1R, DPP4, FBPase and xanthine oxidase are also investigated. Corresponding In vivo pharmacodynamic studies platform are also be set up.
2.A class of small molecule antagonists of GPR40 was discovered in our lab. We used one of them, DC260126, as a probe to investigate the pharmacological mechanisms. Our results suggest that Inhibition of GPR40 by DC260126 could protect against pancreatic β-cells dysfunction and increases insulin sensitivity. Both GPR40 antagonists and GPR40-deficient by gene interference could protect MIN6 β-Cells from palmitate-induced apoptosis.
3.Series of small molecule compounds including natural products were found to protect pancreatic β cells. For example, Cinnamtannin D-1 from Cinnamon species protects pancreatic β-cells from palmitate-induced apoptosis and reverses palmitate-induced dysfunction of glucose-stimulated insulin secretion in primary cultured islets. These results contributed to a better understanding to the mechanisms for the anti-diabetic effects of procyanidin oligomers.
4.Using the FABP4 activity and selectivity evaluation platform, four series of novel FABP4 small molecule inhibitors with solid intellectual property rights have been obtained, which have significant anti-diabetic effects and provide a basis for target confirmation and drug development; At the same time, by explaining the role of FABP4 in the development of obesity-induced T2DM, it provides new thoughts and methods for clinical prevention and treatment of T2DM.
5.Through screening and structural optimization, we finally obtained the DGAT1 small molecule inhibitor with solid intellectual property rights and entered the preclinical research. The compound Yhhu2407 has the characteristics of novel structure, excellent inhibitory activity of DGAT1, significant efficacy in vivo and in vitro and unique metabolic advantages. It can be further developed as a candidate drug for new lipid-lowering drugs.
6.Several xanthine oxidase inhibitors with good development prospects for anti-hyperuricemia were discovered. Melanin metabolism was also concerned and several nature products to alter melanin production were discovered, they may become promising pigmentation-altering agents for pigmentation disorders.
7.Collaborating with chemical scientists in different enterprises and institutes, we carried out a number of pharmacological pharmacodynamic studies, and completed the preclinical evaluation items of several compounds.
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Social Titles
Vice President of Ethnic Minorities Association of Shanghai Science and Technology
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Awards & Honors
Shanghai Pharmaceutical Association, Shanghai pharmaceutical science and Technology Award, the third-prize
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Pubilcations
Full Publication List
Selected Publications
(part of the published articles in recent 5 years)
1. Liu Yang, Xian-Tao Lei, Qi Huang, Ting Wang* , Hong-Bin Sun**, He-Yao Wang*. A novel GPR120-selective agonist promotes insulin secretion and improves chronic inflammation. Life Sciences, 2021 Jan 12;269:119029.
2. Jun-Shang Huang, Bin-Bin Guo, Fei-Fei Lin, Li-Min Zeng, Ting Wang, Xiang-Yu Dang, Yang Yang, You-Hong Hu,* Jia Liu,* He-Yao Wang*. A novel low systemic diacylglycerol acyltransferase 1 inhibitor, Yhhu2407, improves lipid metabolism. European Journal Pharmaceutical Sciences, 2021,158:105683.
3. Xin-Yi Wang, Bo-Rong Zhu, Qi Jia, Yi-Ming Li,* Ting Wang,* and He-Yao Wang*, Cinnamtannin D1 Protects Pancreatic β？Cells from GlucolipotoxicityInduced Apoptosis by Enhancement of Autophagy In Vitro and In Vivo. Journal of Agricultural and Food Chemistry, 2020, 68(45):12617-12630.
4. Jun-shang Huang, Bin-bin Guo, Gai-hong Wang, Li-min Zeng, You-hong Hu, Ting Wang*, He-yao* Wang, DGAT1 inhibitors protect pancreatic β-cells from palmitic acid-induced apoptosis. Acta Pharmacologica Sinica, 2020 Jul 31. doi: 10.1038/s41401-020-0482-7. Online ahead of print.
5. Dou, Hui-Xia; Wang, Ting; Su, Hai-Xia; Gao, Ding-Ding; Xu, Ye-Chun; Li, Ying-Xia; Wang, He-Yao*. Exogenous FABP4 interferes with differentiation, promotes lipolysis and inflammation in adipocytes. Endocrine, 2020, 67(3): 587-596.
6. Sun, Peng; Li, Kai; Wang, Ting; Ji, Jun; Wang, Yan; Chen, Kai-Xian; Jia, Qi; Li, Yi-Ming*; Wang, He-Yao*. Procyanidin C1, a Component of Cinnamon Extracts, Is a Potential Insulin Sensitizer That Targets Adipocytes. Journal of Agricultural and Food Chemistry, 2019, 67(32): 8839-8846.
7. He, Yu-long; Dou, Hui-xia; Gao, Ding-ding; Wang, Ting; Zhang, Ming-ming*; Wang, He-yao*; Li, Ying-Xia*. Identification of new dual FABP4/5 inhibitors based on a naphthalene-1-sulfonamide FABP4 inhibitor. Bioorganic & Medicinal Chemistry, 2019, 27(19): 0-UNSP 115015.
8. Sheng, Ren; Yang, Liu; Zhang, Yan-Chun; Xing, En-Ming; Shi, Rui; Wen Xiao-An; Wang, He-Yao*; Sun, Hong-Bin* Discovery of novel selective GPR120 agonists with potent anti-diabetic activity by hybrid design. Bioorganic & Medicinal Chemistry Letters, 2018, 2018(28): 2599-2604.
9. Gao, Ding-Ding; Dou, Hui-Xia; Su, Hai-Xia; Zhang, Ming-Ming; Wang, Ting; Liu, Qiu-Feng; Cai, Hai-Yan; Ding, Hai-Peng; Yang, Zhuo; Zhu, Wei-Liang*; Xu, Ye-Chun*; Wang, He-Yao*; Li, Ying-Xia* From hit to lead: Structure-based discovery of naphthalene-1-sulfonamide derivatives as potent and selective inhibitors of fatty acid binding protein 4. European Journal of Medicinal Chemistry, 2018, 2018(154): 44-59.
10. Sun, Peng; Zhu, Jing-Jie; Wang, Ting; Huang, Qi; Zhou, Yu-Ren; Yu, Bang-Wei; Jiang, Hua-Liang; Wang, He-Yao*. Benzbromarone aggravates hepatic steatosis in obese individuals. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2018, 1864(6): 2067-2077.
11. Pu, De-Bing; Wang, Ting; Zhang, Xing-Jie; Gao, Jun-Bo; Zhang, Ru-Han; Li, Xiao-Nian; Wang, Yong -Mei; Li, Xiao-Li*; Wang, He-Yao*; Xiao, Wei-Lie*. Isolation, identification and bioactivities of abietane diterpenoids from Premna szemaoensis. RSC Advances, 2018, 8(12): 6425-6435.
12. Cai, Hai-Yan; Wang, Ting; Yang, Zhuo; Xu, Zhi-Jian; Wang, Gui-Min; Wang, He-Yao*; Zhu, Wei-Liang*; Chen, Kai-Xian. Combined Virtual Screening and Substructure Search for Discovery of Novel FABP4 Inhibitors. Journal of Chemical Information and Modeling, 2017, 57(9): 2329-2335.
13. Yan, Jian-Wei; Wang, Gai-Hong; Dang, Xiang-Yu; Guo, Bin-Bin; Chen, Wu-Hong; Wang, Ting; Zeng, Li-Min; Wang, He-Yao*; Hu, You-Hong*. Discovery of a low-systemic-exposure DGAT-1 inhibitor with a picolinoylpyrrolidine-2-carboxylic acid moiety. Bioorganic & Medicinal Chemistry, 2017, 25(17): 4701-4714.
14. Huang, Qi; Wang, Ting; Yang, Liu; Wang, He-Yao*. Ginsenoside Rb2 Alleviates Hepatic Lipid Accumulation by Restoring Autophagy via Induction of Sirt1 and Activation of AMPK. International Journal of Molecular Sciences, 2017, 18(5): 1063.
15. Zhu, Jing-Jie; Huang, Jun-Shang; Wang, Ting; Ji, Jun; Hou, Ai-Jun*; Wang, He-Yao*. Sanggenol F exerts anti-diabetic effects via promoting adipocyte differentiation and modifying adipokines expression. Endocrine, 2017, 56(1): 73-81.
16. Huang, Qi; Wang, Ting; Wang, He-Yao*. Ginsenoside Rb2 enhances the anti-inflammatory effect of omega-3 fatty acid in LPS-stimulated RAW264.7 macrophages by upregulating GPR120 expression. Acta Pharmacologica Sinica, 2017, 38(2): 192-200.
17. Li, He; Huang, Qi; Chen, Cheng; Xu, Bin; Wang, He-Yao*; Long, Ya-Qiu*. Discovery of Potent and Orally Bioavailable GPR40 Full Agonists Bearing Thiophen-2-ylpropanoic Acid Scaffold. Journal of Medicinal Chemistry, 2017, 60: 2697-2717.
18. Li, Yi-Su; Guo, Bin-Bin; Xu, Zhi-Jian*; Li, Bo; Cai, Ting-Ting; Zhang, Xin-Ben; Yu, Yu-Qi; Wang, He-Yao*; Shi, Ji-Ye; Zhu, Wei-Liang*. Repositioning organohalogen drugs: a case study for identification of potent B-Raf V600E inhibitors via docking and bioassay. Scientific Reports, 2016, 6: 31074.
19. Sun, Peng; Wang, Ting; Chen, Lu; Yu, Bang-Wei; Jia, Qi; Chen, Kai-Xian; Fan, Hui-Min; Li, Yi-Ming*; Wang, He-Yao*. Trimer procyanidin oligomers contribute to the protective effects of cinnamon extracts on pancreatic beta-cells in vitro. Acta Pharmacologica Sinica, 2016, 37(8): 1083-1090.
20. Yu, Bang-Wei; Li, Jin-Long; Guo, Bin-Bin; Fan, Hui-Min*; Zhao, Wei-Min*; Wang, He-Yao*. Chlorogenic acid analogues from Gynura nepalensis protect H9c2 cardiomyoblasts against H2O2-induced apoptosis. Acta Pharmacologica Sinica, 2016, 37(11): 1413-1422.
21. Ji, Jun; Zhu, Jing-Jie; Hu, Xiao; Wang, Ting; Zhang, Xiao-Dong; Hou, Ai-Jun*; Wang, He-Yao* (2S)-7,4'-dihydroxy-8-prenylflavan stimulates adipogenesis and glucose uptake through p38MAPK pathway in 3T3-L1 cells. Biochemical and Biophysical Research Communications, 2015, 460(3): 578-582.
22. Jiang, Tao; Zhou, Yu-Ren; Chen, Zhu-Xi; Sun, Peng; Zhu, Jian-Ming; Zhang, Qiang; Wang, Zhen; Shao, Qiang; Jiang, Xiang-Rui; Li, Bo; Chen, Kai-Xian; Jiang, Hua-Liang; Wang, He-Yao*; Zhu, Wei-Liang*; Shen, Jing-Shan*. Design, Synthesis, and Pharmacological Evaluation of Fused beta-Homophenylalanine Derivatives as Potent DPP-4 Inhibitors. ACS Medicinal Chemistry Letters, 2015, 6(5): 602-606.
23. Zhou, Yu-Ren; Sun, Peng; Wang, Ting; Chen, Kai-Xian; Zhu, Wei-Liang*; Wang, He-Yao*. Inhibition of Calcium Influx Reduces Dysfunction and Apoptosis in Lipotoxic Pancreatic beta-Cells via Regulation of Endoplasmic Reticulum Stress. PLos One, 2015, 10(7): e0132411-e0132411.
24. Chen, Lu; Chen, Liang; Wang, Ting; Yuan Pu-Long; Chen, Kai-Xian; Jia, Qi*; Wang He-Yao *; and Li, Yi-Ming *. Preparation of Methylated Products of A-type Procyanidin Trimersin Cinnam on Bark and Their Protective Effects on Pancreatic β-Cell. Journal of Food Science, 2016, 81(5): C1063-9.
25. Zhu, Jing-Jie; Yan, Gui-Rui; Xu, Zhi-Jian; Hu, Xiao; Wang, Gai-Hong; Wang, Ting; Zhu, Wei-Liang; Hou, Ai-Jun*; Wang, He-Yao*. Inhibitory Effects of (2'R)-2',3'-dihydro-2'- (1-hydroxy-1–methylethyl)-2,6'-bibenzofuran-6,4'-diol on Mushroom Tyrosinase and Melanogenesis in B16-F10 Melanoma Cells. Phytotherapy Research, 2015, 29(7): 1040-1045.
26. Cai, Hai-Yan; Liu, Qiu-Feng; Gao, Ding-Ding; Wang, Ting; Chen, Tian-Tian; Yan, Gui-Rui; Chen, Kai-Xian; Xu, Ye-Chun*; Wang, He-Yao*; Li, Ying-Xia*; Zhu, Wei-Liang*. Novel fatty acid binding protein 4 (FABP4) inhibitors: virtual screening, synthesis and crystal structure determination. European Journal of Medicinal Chemistry, 2015, 90: 241-250.
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