Zhong-Yin Zhang

Zhong-Yin Zhang Profile Picture

Distinguished Professor and Head, Medicinal Chemistry and Molecular Pharmacology, Director, Purdue Institute for Drug Discovery
Ph.D. Purdue University 1990

Contact Info:

DRUG Rm223

Training Group(s):
Chemical Biology
Biomolecular Structure and Biophysics
Computational and Systems Biology
Cancer Biology

Active Mentor - currently hosting PULSe students for laboratory rotations and recruiting PULSe students into the laboratory; serves on preliminary exam committees

Current Research Interests:

Structure/Function and Therapeutic Targeting of Protein Tyrosine Phosphatases Our research is focused on protein tyrosine phosphatases (PTPs), signaling enzymes that regulate cellular homeostasis. Alteration of PTP activity leads to aberrant cellular signaling, which is linked to cancer, diabetes and autoimmune disorders. Consequently, there is heightened interest to control disease progression at the level of PTPs. We seek to fully characterize the PTP family, understanding how PTP activity is controlled and how PTP malfunction causes diseases. To accomplish this goal, we employ a combination of approaches including biochemistry, molecular and cell biology, structural biology, and mouse genetics. To advance therapeutic targeting of the PTPs as a target class, we employ high-throughput screening, fragment- and structure-based design, and medicinal chemistry to develop PTP inhibitors for functional interrogation, target validation, and therapeutic development. Current efforts aim to advance our target validation and lead generation paradigms and to create a ‘PTP-based drug discovery platform’ that will ultimately impact the portfolio of tomorrow.

Selected Publications:

Walls, C., Iliuk, A., Bai, Y., Wang, M., Tao, A. and Zhang, Z.-Y. "Phosphatase of Regenerating Liver 3 (PRL3) Provokes a Tyrosine Phosphoproteome to Drive Pro-Metastatic Signal Transduction", Molecular and Cellular Proteomics 12, 3759-3777 (2013).

Dong, Y., Zhang, L., Bai, Y., Zhou, H.-M., Campbell, A. M., Chen, H., Yong, W., Zhang, W., Zeng, Q., Shou, W., and Zhang Z.-Y. "Phosphatase of regenerating liver 2 (PRL2) deficiency impairs Kit signaling and spermatogenesis", J. Biol. Chem. 289, 3799-3810 (2014).

Zeng, L.-F., Zhang, R.-Y., Yu, Z.-H., Liu, S., Wu, L., Gunawan, A. M., Lane, B. S., Mali, R. S., Li, X., Chan, R. J., Kapur, R., Wells, C. D., and Zhang, Z.-Y. "Therapeutic potential of targeting oncogenic SHP2 phosphatase", J. Med. Chem. 57, 6594-6609 (2014).

He, R., Yu, Z.-H., Zhang, R.-Y., Wu, L., Gunawan, A., Lane, B. S., Shim, J. S., Zeng, L.-F., He, Y., Chen, L., Wells, C. D., Liu, J. O., and Zhang, Z.-Y. "Exploring the existing drug space for novel pTyr mimetic and SHP2 inhibitors", ACS Med. Chem. Lett. 6, 782-786 (2015).

Bunda, S., Burrell, K., Heir, P., Zeng, L.-F., Alamsahebpour, A., Kano, Y., Raught, B., Zhang, Z.-Y., Zadeh, G., and Ohh, M. "Inhibition of SHP2-mediated dephosphorylation of Ras suppresses oncogenesis", Nature Communications 6, 8859 (2015).

He, R., Yu, Z.-H., Zhang, R.-Y., Wu, L., Gunawan, A. M., and Zhang, Z.-Y. "Cefsulodin inspired potent and selective inhibitors of mPTPB, a virulent phosphatase from Mycobacterium tuberculosis", ACS Med. Chem. Lett. 6, 1231-1235 (2015).

Bai, Y., Yu, Z., Liu, S., Zhang, L., Zhang, R.-Y., Zeng, L.-F., Zhang, S., and Zhang, Z.-Y. “Novel anticancer agents based on targeting the trimer interface of the PRL phosphatase”, Cancer Res. 76, 4805-4815 (2016).

Zhang, R.-Y., Yu, Z.-H., Zeng, L.-F., Zhang, S., Bai, Y., Miao, J., Chen, L., Xie, J. and Zhang, Z.-Y. “SHP2 phosphatase as a novel target for melanoma treatment”, Oncotarget 7, 73817-73829 (2016).

Bai, Y., Zhou, H.-M., Zhang, L., Dong, Y., Zeng, Q., Shou, W., and Zhang, Z.-Y. “Role of Phosphatase of Regenerating Liver 1 (PRL-1) in spermatogenesis”, Scientific Reports 6, 34211 (2016).

He, R., Wang, J., Yu, Z.-H., Zhang, R.-Y., Liu, S., Wu, L., and Zhang, Z.-Y. “Inhibition of low molecular weight protein tyrosine phosphatase by an induced-fit mechanism”, J. Med. Chem. 59, 9094-9106 (2016).

Zhang, Z.-Y. “Drugging the undruggable: therapeutic potential of targeting protein tyrosine phosphatases”, Acc. Chem. Res. 50, 122-129 (2017).

Kobayashi, M., Chen, S., Bai, Y., Yao, C., Gao, R., Sun, X.-J., Mu, C., Twiggs, T., Yu, Z. H., Boswell, H. S., Yoder, M. C., Kapur, R., Mulloy, J. C., Zhang, Z.-Y., and Liu, Y. “Phosphatase PRL2 promotes AML1-ETO-induced acute myeloid leukemia”, Leukemia 31 1453-1457 (2017).

Frankson, R., Yu, Z.-H., Bai, Y., Li, Q., Zhang, R.-Y., Zhang, Z.-Y. “Therapeutic targeting of oncogenic tyrosine phosphatases”, Cancer Research 77, 5701-5705 (2017).

Yu, Z.-H., and Zhang, Z.-Y. “Regulatory mechanisms and novel therapeutic targeting strategies for protein tyrosine phosphatases” Chemical Reviews 118, 1069-1091 (2018).

Zhang, R.-Y., Yu, Z.-H., Chen, L., Walls, C. D., Zhang, S., Wu, L., and Zhang, Z.-Y. “Mechanistic insights explain the transforming potential of the T507K substitution in the protein tyrosine phosphatase SHP2”, J. Biol. Chem. 295, in press (2020).


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