Yong (Tiger) Zhang, PhD
Assistant ProfessorPharmacology and Pharmaceutical SciencesCurriculum Vitae
- Chemical Biology
- Drug Design and Discovery
- Antibody Engineering
- Protein Biosynthesis
- Cancer, Diabetes and Neurodegeneration
B.S. 2003 Biological Sciences - Shandong University, China
M.S. 2006 Biophysics - University of Guelph, Canada
Ph.D. 2011 Biochemistry - Albert Einstein College of Medicine, Bronx, NY
Postdoctoral 2011-2014 - The Scripps Research Institute; California Institute for Biomedical Research, La Jolla, CA
Protein post-translational modifications (PTMs) result in critical changes on protein structure and biological function. The broad range of PTMs observed on various proteins vastly diversifies the inventory of organism proteome. Furthermore, highly abundant PTMs with dynamic pattern play essential and complex roles in biological processes. Our laboratory is very interested in developing innovative technologies to systematically dissect PTMs essential for cancer, inflammation, neurodegeneration and immune disorders for understanding the functional consequences and regulatory mechanisms of PTMs and for discovery of novel therapeutic targets and drug inhibitors.
Antibody recognizes and neutralizes foreign pathogens and is an important component in immune system. The exquisite specificity and tight-binding affinity of monoclonal antibodies make antibody-based therapeutics ideal drug candidates. Development of monoclonal antibodies against ligands, receptors, and protein-protein interactions that play critical roles in various human diseases allows discovery of powerful therapeutic agents with minimum off-target effects. We are aimed at designing potent monoclonal antibodies with high specificity as novel immunotherapeutic tools for cancer, immune disorders, neurodegenerative, and infectious diseases, and developing new and robust protein engineering approaches for efficient generation of potent polypeptide-based diagnostics and therapeutics.
Graduate students can receive direct and extensive training from PI in antibody engineering, enzymology and catalysis, inhibitor design and synthesis, protein expression, purification and characterization, cell culturing, assay development, proteomics, X-ray crystallography and NMR, pharmacokinetics and pharmacodynamics, and high-throughput screening. Upon graduation, students are expected to possess multiple sets of skills and strong publication record, essential for career development in both academia and industry.
Dr. Zhang received his B.S. in Biological Sciences from Shandong University in 2003 and his M.S. in Biophysics from University of Guelph in 2006. He earned his Ph.D. in Biochemistry with Professor Vern L. Schramm at Albert Einstein College of Medicine in 2011. His doctoral research was focused on the enzymatic transition state and catalytic mechanism for rational design of potent enzyme inhibitors as antimalarial and anticancer drugs. Dr. Zhang received postdoctoral training with Professor Peter G. Schultz at the Scripps Research Institute and California Institute for Biomedical Research (Calibr) from 2011 to 2014. His postdoctoral work established a versatile approach to the generation of novel antibody chimeras with excellent physical, biological, and pharmacological properties for drug development. Dr. Zhang joined the faculty in the Department of Pharmacology and Pharmaceutical Sciences at USC School of Pharmacy as an Assistant Professor in December 2014.
Zhang, X.N., Cheng, Q., Chen, J., Lam, A.T., Lu, Y., Dai, Z., Pei, H., Evdokimov, N.M., Louie, S.G. and Zhang, Y. A Ribose-Functionalized NAD+ with Unexpected High Activity and Selectivity for Protein Poly-ADP-Ribosylation. Nat. Commun. 2019, 10, 4196. PubMed -Link
Dai, Z., Zhang, X.N., Nasertorabi, F., Cheng, Q., Pei, H., Louie, S.G., Stevens, R.C. and Zhang, Y. Facile Chemoenzymatic Synthesis of a Novel Stable Mimic of NAD+. Chem. Sci. 2018, 9, 8337-8342 Featured in Front Cover PubMed -Link
Cheng, Q., Shi, X., Han, M., Smbatyan, G., Lenz, H.J. and Zhang, Y. Reprogramming Exosomes as Nanoscale Controllers of Cellular Immunity. J. Am. Chem. Soc. 2018, 140, 16413-16417 PMID30452238 PubMed -Link
Du, J., Cao Y., Liu, Y., Wang, Y., Zhang, Y., Fu, G., Zhang, Y., Lu, L., Luo, X., Kim, C.H., Schultz, P.G. and Wang, F. Engineering Bifunctional Antibodies with Constant Region Fusion Architectures. J. Am. Chem. Soc., 2017, 139, 18607–18615 PubMed -Link
Liu, Y., Wang, Y., Zhang, Y., Liu, T., Jia, H., Zou, H., Fu, Q., Zhang, Y., Lu, L., Chao, E., Parker, H., Nguyen-Tran, V.T.B., Shen, W., Wang, D., Schultz, P.G. and Wang, F. Rational Design of Dual Agonist-Antibody Fusions as Long-Acting Therapeutic Hormones. ACS Chem. Biol., 2016, 11, 2991-2995. PubMed -Link
Wang, R.E., Wang, Y., Zhang, Y., Gabrelow, C., Zhang, Y., Chi, V., Fu, Q., Luo, X., Wang, D., Joseph, S., Johnson, K., Chatterjee, A.K., Wright, T.M., Nguyen-Tran, V.T.B., Teijaro, J., Theofilopoulos, A.N., Schultz, P.G. and Wang, F. Rational Design of a Kv1.3 Channel-Blocking Antibody as a Selective Immunosuppressant. Proc. Natl. Acad. Sci. U.S.A., 2016, 113, 11501-11506 PubMed -Link
Zhang, Y., Zou, H., Wang, Y., Caballero, D., Gonzalez, J., Chao, E., Welzel, G., Shen, W., Wang, D., Schultz, P.G. and Wang, F. Rational Design of a Humanized Glucagon-Like Peptide-1 Receptor Agonist Antibody. Angew. Chem. Int. Ed. Engl., 2015, 54, 2126-30. PubMed -Link
Liu, T., Zhang, Y. (co-first author), Liu, Y., Wang, Y., Jia, H., Kang, M., Luo, X., Caballero, D., Gonzalez, J., Wang, D., Woods, A., Schultz, P.G. and Wang, F. Functional Human Antibody CDR Fusions as Long-Acting Therapeutic Endocrine Agonists. Proc. Natl. Acad. Sci. U.S.A., 2015,112,1356-61. PubMed -Link
Zhang, Y., Goswami, D., Wang, D., Wang, T.S.A., Sen, S., Magliery, T.J., Griffin, P.R., Wang, F. and Schultz, P.G. An Antibody with a Variable Region Coiled-Coil “Knob” Domain. Angew. Chem. Int. Ed. Engl., 2014, 53, 132-135. PubMed -Link
Zhang, Y., Evans, G.B., Clinch, K., Crump, D.R., Harris, L.D., Fröhlich, R.F.G., Tyler, P.C., Hazleton, K.Z., Cassera, M.B. and Schramm, V.L. Transition State Analogues of Plasmodium falciparum and Human Orotate Phosphoribosyltransferases. J. Biol. Chem., 2013, 288, 34746-54. PubMed -Link
Zhang, Y., Wang, D., de Lichtervelde, L., Sun, S.B., Smider, V.V., Schultz, P.G. and Wang, F. Functional Antibody CDR3 Fusion Proteins with Enhanced Pharmacological Properties. Angew. Chem. Int. Ed. Engl., 2013, 52, 8295-8298. PubMed -Link
Wang, F., Ekiert, D.C., Ahmad, I., Li, W., Zhang, Y., Bazirgan, O., Torkamani, A., Raudsepp, T., Mwangi, W., Criscitiello, M.F., Wilson, I.A., Schultz, P.G. and Smider. V.V. Reshaping Antibody Diversity. Cell, 2013, 153, 1379-93. PubMed -Link
Zhang, Y., Deng, H. and Schramm, V.L. Leaving Group Activation and Pyrophosphate Ionic State at the Catalytic Site of Plasmodium falciparum Orotate Phosphoribosyltransferase. J. Am. Chem. Soc., 2010, 132, 17023-17031. PubMed -Link
Zhang, Y. and Schramm, V.L. Pyrophosphate Interactions at the Transition States of Plasmodium falciparum and Human Orotate Phosphoribosyltransferases. J. Am. Chem. Soc., 2010, 132, 8787-8794. PubMed -Link
Zhang, Y. (co-first author), Liu, S., Lajoie G. and Merrill, A.R. The Role of the Diphthamide-containing Loop within Eukaryotic Elongation Factor 2 in ADP-Ribosylation by Pseudomonas aeruginosa Exotoxin A. Biochem. J., 2008, 413, 163-174. PubMed -Link