Time：2017-12-31 Browse times：669
Affiliation: State Key Laboratory of Natural Medicines.
Key Lab of Drug Metabolism and Pharmacokinetics,
China Pharmaceutical University, Nanjing, 210009, China.
Group website: https://yegroup.top/
Ph.D. Pharmaceutical Science major (Supervisor: Prof. Lingjun Li), May 2013
School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA
B.S. Chemistry major June 2008 Sichuan University Chengdu Sichuan P. R. China
Metabolomics, Chemical proteomics, Structural mass spectrometry
My research focuses on developing and implementing an array of novel analytical tools in the area of metabolomics and chemical proteomics to elucidate the direct binding targets of small molecules including natural medicines and endogenous metabolites, and gain new insights into how these functional molecules regulate protein function and signaling network. The gained knowledge is thus utilized to design and synthesize novel ligands that allow modulating the structures and hence the activities of the target proteins that are intimately associated with diseases such as cancer and immune diseases.
Innovative Drugs Young Scholar Professor Aug. 2020, China Pharmaceutical University, P. R. China
Associate Professor Jan. 2016, Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, P. R. China
Research Associate Jul. 2013-Dec. 2015, School of Pharmacy, China Pharmaceutical University, P. R. China
•Young Scientific and Technological Talents Support Project of Jiangsu Provincial Association for Science and Technology (2019)
• Six Talent Peaks Project of Jiangsu Province (2018)
• Science Foundation for The Excellent Youth Scholars in Jiangsu Province (2018)
• University of Wisconsin-Madison Vilas Travel Award (2012)
•Zhu Y‡, Wan N‡, Shan X, Deng G, Xu Q, Ye H*, Sun Y*. Celastrol targets adenylyl cyclase-associated protein 1 to reduce macrophages-mediated inflammation and ameliorates high fat diet-induced metabolic syndrome in mice. Acta Pharm Sin B. 2021; 11(5):1200-1212.
•Shao C, Lu W, Hao H*, Ye H*. Functional Metabolomics and Chemoproteomics Approaches Reveal Novel Metabolic Targets for Anticancer Therapy. Advan Exp Med Biol. 2021; 1280:131-147.
•Sang H‡ , Liu Jl‡ , Zhou F, Zhang XF, Zhang JW, Liu YZ, Wang GJ*, Ye H*. Target-responsive subcellular catabolism analysis for early-stage antibody‒drug conjugates screening and assessment. Acta Pharm Sin B. 2021; Doi: https://doi.org/10.1016/j.apsb. 2021.05.024.
•Shao C, Lu W, Du Y, Yan W, Bao Q, Tian Y, Wang G, Ye H*, Hao H*. Cytosolic ME1 integrated with mitochondrial IDH2 supports tumor growth and metastasis. Redox Biol. 2020; 36:101685.
•Tian Y‡, Wan N‡, Ding M, Shao C, Wang N, Bao QY, Lu WJ, Hu HY, Sun HY, Yang CX, Zhou K, Chen S, Wang GJ, Ye, H*, Hao, HP*. Chemoproteomics Maps Glycolytic Targetome in Cancer Cells. bioRxiv. 2020.11.18.387670.
•Lu G, Xu X, Li G, Sun H, Wang N, Zhu Y, Wan N, Shi Y, Wang G, Li L, Hao H*, Ye H*. Subresidue-Resolution Footprinting of Ligand-Protein Interactions by Carbene Chemistry and Ion Mobility-Mass Spectrometry. Anal Chem. 2020; 92(1):947-956.
•Shao C‡, Lu W‡, Wan N‡, Wu M‡, Bao Q, Tian Y, Lu G, Wang N, Hao H*, Ye H*. Integrative Omics Analysis Revealed that Metabolic Intervention Combined with Metronomic Chemotherapy Selectively Kills Cancer Cells. J Proteome Res. 2019; 18(6):2643-2653.
•Zheng Q‡, Tian Y‡, Ruan X, Chen H, Wu X, Xu X, Wang G, Hao H*, Ye H*. Probing specific ligand-protein interactions by native-denatured exchange mass spectrometry. Anal Chim Acta. 2018; 1036:58-65.
•Li Q‡, Cao L‡, Tian Y, Zhang P, Ding C, Lu W, Jia C, Shao C, Liu W, Wang D, Ye H*, Hao H*. Butyrate Suppresses the Proliferation of Colorectal Cancer Cells via Targeting Pyruvate Kinase M2 and Metabolic Reprogramming. Mol Cell Proteomics. 2018; 17(8):1531-1545.
•Ye H‡, Wang J‡, Tian Z, Ma F, Dowell J, Bremer Q, Lu G, Baldo B*, Li L*. Quantitative Mass Spectrometry Reveals Food Intake-Induced Neuropeptide Level Changes in Rat Brain: Functional Assessment of Selected Neuropeptides as Feeding Regulators. Mol Cell Proteomics. 2017; 16(11):1922-1937.
•Wang L‡, Ye H‡, Sun D, Meng T, Cao L, Wu M, Zhao M, Wang Y, Chen B, Xu X, Wang G*, Hao H*. Metabolic Pathway Extension Approach for Metabolomic Biomarker Identification. Anal Chem. 2017; 89(2):1229-1237.
•Ye H, Gemperline E, Venkateshwaran M, Chen R, Delaux PM, Howes-Podoll M, Ané JM, Li L*. MALDI mass spectrometry-assisted molecular imaging of metabolites during nitrogen fixation in the Medicago truncatula-Sinorhizobium meliloti symbiosis. Plant J. 2013; 75(1):130-145.
•National Key R&D Program of China (2018YFD0901101)
•National Natural Science Foundation of China (grants 82173783, 81872838, 81403005)
•Natural Science Foundation of Jiangsu province, China (grant BK20180079, BK20140667)
•Scientific Research Foundation for the Returned Overseas Chinese Scholars, Ministry of Education
•Double First-rate University project (CPU2018GF09)
Pioneering work include the development of a modification-free target discovery approach TRAP (Target Responsive Accessibility Profiling, bioRxiv 2020.11.18.387670; doi: https://doi.org/10.1101/2020.11.18.387670). We applied TRAP to map the targetome for glycolytic metabolites in cancer cells, and unveiled a complex metabolite-protein network. Biological validation demonstrated that glycolytic metabolites utilize their targets to allow cancer cells to gain survival and growth advantages.
Another advancement lies in structural MS-based mapping ligand-protein binding topology. We developed a Sub-residue Resolution Footprinting approach to examine ligand-protein interactions by carbene chemistry and Ion Mobility-Mass Spectrometry (Anal Chem. 2020 Jan 7;92(1):947-956. doi: 10.1021/acs.analchem.9b03827). Together, these approaches allow us to gain new insights into how these functional molecules regulate protein function and signaling network.
Using metabolic flux analysis, we noted that the assayed cancer cell lines preferen- tially depend on ME1-mediated NADPH production. ME1 knockdown retarded cancer cell proliferation and increased anoikis, while sparing normal cells. Notably, ME1 interference ultimately resulted in adaptive upregulation of mitochondrial IDH2 dependent of AMPK-FoxO1 activation to replenish the NADPH pool. Combining ME1 ablation and IDH2 inhibition drastically reduced intracellular NADPH and prevented resistance to ME1 interference, resulting in increased apoptosis and impeded tumor growth and metastasis (Redox Biol. 2020 Sep;36:101685. doi: 10.1016/j.redox.2020.101685).