1. Target Identification and Validation in Drug Discovery

Target validation is the basis of new drug exploration and the initial step of drug discovery. Using novel chemical tools, bioorthogonal techniques, and chemical-proteomics, our lab focuses on the interrogating anti-cancer drug-target-phenotype relationships. We want to understand 1) what is the pharmacological target of new drug 2) how this target are important for pathological functions, 3) can we intervene in it to change the behaviors of pathological cells. These efforts are aim to illuminate a new paradigm for the development of new means to treat human diseases.

2. Pharmacological mechanism of ACT001

ACT001, a novel anti-cancer candidate reagent developed by Prof. Chen’s group, has been approved for clinical trials in China and U.S.A. Besides its anti-cancer effect, ACT001 has other bioactivity towards attenuating cardiotoxicity, immune regulation and multi-organ radioprotection. We want to clarify these pharmacological mechanisms of ACT001 in vitro and in vivo.  

3.Chemical Glycobiology 

Glycobiology is a new area which includes glycans and glycoconjugates that comprise cell cytoskeleton, molecules for energy storage and elaborate surface structures that help pathogens evade the host immune response. We want to explore novel probe to track, capture, identify any interesting molecular in glycobilogy.

1997.9-2001.7 Shandong Agriculture University，B.S., P. R. China;

2001.7-2007.7: Shandong Agriculture University, Ph. D., P. R. China;

2004.9-2007.7: Shandong University (exchange student);

2007.7- 2020.10: Associate prof. at College of Pharmacy， Nankai University, Tianjin, P. R. China.

2014.9-2016.8: Postdoctoral fellow ， Georgia state University,U.S.A.;

2020.10-Present:  Prof. at College of Chemistry， Nankai University, Tianjin, P. R. China.

[1] Ding Y, Xue Q, Liu S, Hu K, Wang D, Wang T, Li Y, Guo H, Hao X, Ge W, Zhang Y, Li A, Li J*, Chen Y*, Zhang Q*. Identification of Parthenolide Dimers as Activators of Pyruvate Ki-nase M2 in Xenograft of Glioblastoma Multiforme in vivo. Journal of Medicinal Chemistry 2020 63 (4): 1597-1611 

[2] Guo J., Xue Q., Ma J., Liu K., Ge W., Liu W., Wang J., Zhang M., Li Q., Cai D., Shan C., Zhang C., Liu X., Li J.*, Dimethylaminomicheliolide (DMAMCL) Suppresses the Proliferation of Glioblastoma Cells via Targeting Pyruvate Kinase 2 (PKM2) and Rewiring Aerobic Glycolysis. Frontiers in Oncology, 2019, 9: 993.

[3] Guo J., Zhang G., Ma J., Zhao C., Xue Q., Wang J., Liu W., Wang H., Liu N., Song Q., Li J.*, A detection and identification of O-GlcNAc-modified proteins using 6-azido-6-deoxy-N-acetyl-galactosamine. Organic & Biomolecular Chemistry, 2019,17, 4326-4334.

[4] Li S., Wang J.*, Zang L., Zhu H., Guo J.,Zhang J., Wen L., Chen Y.,Li Y., Chen X., Wang P G.*, Li J.*,Production of Glycopeptide Derivatives for Exploring Substrate Specificity of Human OGA Toward Sugar Moiety. Frontiers in Chemistry, 2019, 6: 646.

[5] Wang H., Guo J., Wang N., Wang J., Xue Q., Wang J., Liu W., Liu K., Cao X ., Zhao W., Xi R., Niu Y., Wang P., Li J.*, Ac4GlcNAcF3, an OGT-tolerated but OGA-resistant regulator for O-GlcNAcylation.  Bioorganic & Medicinal Chemistry Letters, 2019.2.15, 29(6): 802~805.

[6] Li J., Li S., Guo J., Li Q., Long J., Ma C., Ding Y., Yan C., Li L., Wu Z., Zhu H., Li K., Wen L., Zhang Q., Xue Q., Zhao C., Liu N., Ivanov I., Luo M., Xi R., Long H., Wang PG., Chen Y.., Natural Product Micheliolide (MCL) Irreversibly Activates Pyruvate Kinase M2 and Suppresses Leukemia. Journal of Medicinal Chemistry 2018, 61, 4155−4164.

[7] Jiang K., Zhu H., Li L., Guo Y., Gashash E., Ma C., Sun X., Li J.*, Zhang L.*, Wang PG.*. Sialic acid linkage-specific permethylation for improved profiling of protein glycosylation by MALDI-TOF MS. Analytica Chimica Acta, 2017, 981:53-61.

[8] Jiang K., Zhu H., Xiao C., Liu D., Garrett E., Wen L., Ma C.*, Li J.*, Wang PG.*. Solid-phase reductive amination for glycomic analysis. Analytica Chimica Acta, 2017, 962:32-40. 

[9] Wen L., Jiang K., Zheng Y., Zhang M., Kondengaden SM., Li S., Huang K., Li J., Song J., Wang PG. Two-step Chemoenzymatic Detecting N-Acetylneuraminic acid-α(2-3)- galactose Glycans. JACS, 2016, 138 (36): 11473–11476.

[10] Wu Z., Jiang K., Zhu H., Ma C., Yu Z., Li L., Guan W., Liu Y., Zhu H., Chen Y., Li J., Cheng J., Wang PG., Site-directed glycosylation of peptide/protein with homogeneous O-linked eukaryotic N-glycans. Bioconjugate chemistry 2016, 27 (9), 1972–1975.

[11] Li J., Wen L., Zhu H., Li S., Huang K., Li X., Ma C., Qu J., Parameswaran A., Song J., Zhao W., Wang PG. An OGA-resistant Probe Allow Specific Visualization and Accurate Identification of O-GlcNAc-modified Proteins in Cells. ACS Chem Biol, 2016, 11 (11): 3002–3006.

[12] Li S., Zhu H., Wang J., Wang X., Li X., Ma C., Wen L., Yu B., Wang Y., Li J*., Wang PG.* Comparative analysis of Cu (I)-catalyzed alkyne-azide cycloaddition (CuAAC) and strain-promoted alkyne-azide cycloaddition (SPAAC) in O-GlcNAc proteomics. Electrophoresis. 2016, 37(11): 1431-1436.

[13] Li Z., Li T., Dai S., Xie X., Ma X., Zhao W., Li J.* & Wang P. G*. New insights into the pharmacological chaperone activity of C2 — substituted glucoimidazoles for the treatment of gaucher disease. ChemBioChem, 2013, 14 (10): 1239- 1247.