Dr. Jonathan Zhang is an associate professor of the Bioengineering Department in the School of Engineering at SCU, starting September of 2011. Dr. Zhang received his Ph.D. degree in Chemistry and Biochemistry from University of Texas at Austin in 2001 by developing the first generation E. coli two-hybrid system, engineering epitode-binding peptides, pioneering "substrate-targeted enzyme inhibitors", also known as "molecular cloaking devices". He then did his postdoctoral research in The Scripps research Institute from 2001 to 2004, working on protein engineering via expanding genetic codes and hijacking cellular protein synthesis machinery. Before moving to SCU, from 2004 to 2011, Dr. Zhang has been an assistant professor of Medicinal Chemistry in College of Pharmacy at University of Texas at Austin. In addition to the classroom teaching and services such as executive committee of Graduate Studies Committee of Department of Biomedical Engineering, he has established the highly interdisciplinary research programs at the crossroad of biomolecular and biodevice engineering, biochemistry, chemical biology and drug discovery. His research has been supported by grants from NIH, American Heart Association, Welch Research Foundation, etc.
The theme of research in Dr. Zhang's lab has been "bioengineering towards medicine". The idea is to engineer novel materials (particularly proteins and peptides) and devices and apply them to study basic biological and medical questions that ultimately lead to drug discovery. Research from Dr. Zhang's lab has led to the development of technologies such as trM2H system (tetracycline repressor-based mammalian two-hybrid system), site-specific protein cross-linking technology, peptide-based synthetic antibody equivalents and cell LASIK (with Prof. Shaochen Chen, UCSD). Using these technologies, his lab first discovered and then studied the dimerization of Staphylococcus aureus membrane transpeptidase sortase A, a therapeutic target for antibiotics discovery. Cell-based high throughput screening (HTS) of chemical libraries has afforded small molecule candidates for antiinfective treatment. Dr. Zhang has filed /been awarded eight US and international patents and he has been invited to serve as technical consultant for biotech and pharmaceutical companies.
Current Research Areas
- Protein Engineering: Expanding genetic codes in mammalian cells and stem cells; Engineering synthetic biomarker-recognizing reagents
- Reverse Protein Engineering: Searching for a "Peptide World"
- Biodevice / Bioinstrument Engineering: Applications of cell LASIK, label-free protein chip engineering
- Anti-infective drug discovery
- Biomolecular Engineering I (BIOE 175) labs (BIOE175L)
- Biomolecular Engineering II (BIOE 176)
- Biodevice Engineering (BIOE 163) labs (BIOE 163L)
- Biomaterial Engineering (BIOE 153)
- Senior Design Projects (BIOE 194, 195, 196)
- Biotechnology (BIOE 186/286 graduate)
- Clinical Biomaterial Engineering (BIOE 386 graduate)
NIH/NCI R01, NIH SBIR, Rober A. Welch Research Foundation, American Heart Association, IBM Research Grant.
- Zhang, Z., Murphy, A., Hu, J., Kodadek, T. Genetic selection of short peptides that support protein oligomerization in vivo. Curr. Biol., 1999, 9, 417- 420.
- Zhang, Z., Zhu, W., Kodadek, T. Selection and application of peptide-binding peptides. NatureBiotechnol., 2000,18, 71-74.
- Zhang, Z., Ly, T., Kodadek, T. Inhibition of sequence-specific proteolysis using compounds thattarget the substrate rather than the enzyme. Chem. Biol., 2001,8, 391-397.
- Zhang, Z., Wang, L., Brock, A., Schultz, P. The Selective Incorporation of Alkenes into Proteins inEscherichia coli, Angew. Chem. Intl., 2002, 41, 2840-2842.
- Wang, L., Zhang, Z., Brock, A., Schultz, P. Addition of the keto functional group to the genetic codeof Escherichia coli, Proc. Natl. Acad. Sci. USA, 2003, 100,56-61.
- Zhang, Z., Smith, B. A., Wang, L., Brock, A., Schultz, P. A new strategy for site-specific proteinmodification in vivo: genetic incorporation of keto amino acids into proteins. Biochemistry, 2003,42, 6735-6746.
- Chin, J. W., Cropp, T. A., Anderson, J. C., Mukhergi, M., Zhang, Z., Schultz, P. An expandedeukaryotic genetic code. Science, 2003, 301, 964-967.
- Alfonta, L., Zhang, Z., Uryu, S., Schultz, P.G. Site-specific incorporation ofredox dihydroxy-phenylalanine (DHP) into proteins. J. Am. Chem. Soc. 2003,125, 14662-14663.
- Zhang, Z., Alfonta, L., Feng, T., Uryu, S., Schultz, P.G. Selective incorporation of 5-hydroxy-tryptophan into proteins in mammalian cells. Proc.Natl. Acad. Soc. USA,2004,101, 8882-8887.
- Lu, C., Zhu, J., Wang. Y., Umeda, A., Lai, E., Comeadow, R., Moreno, G., Person, M., Zhang, Z.Staphylococcus aureus sortase A exists as a dimeric protein in vitro. Biochemistry, 2007, 46, 9346-9354.
- Zhu, J., Lu, C., Standland, M., Lai, E., Moreno, G., Umeda, A., Jia, X., Zhang, Z. Single mutation on the surface of Staphylococcus aureus sortase A can disrupt its dimerization. Biochemistry, 2008,47,1667-1674.
- Thibodeaux, G.N., Cowmeadow, R., Umeda, A., Zhang, Z. A tetracycline repressor-basedmammalian two-hybrid system to detect protein-protein interactions in vivo. Anal. Biochem. 2009,368,129-131.
- Umeda, A., Thibodeaux, G.N., Zhu, J., Lee, Y., Zhang, Z. Site-specific protein crosslinking with genetically incorporated 3,4-dihydroxy-L-phenylalanine. ChemBioChem, 2009, 10, 1302-1304.
- Umeda, A., Hou, T., Thibodeaux, G.N., Moncivais, K., Jiang, F., Zhang, Z. A Versatile Approach to Transform Low-Affinity Peptides into Protein Probes with Co-Translationally Expressed Chemical Cross-Linker,Analytical Biochemistry, 2010, 405(1):82-8. (Cover of the journal)
- Thibodeaux, G.N., Cowmeadow, R., Xiang, L., Alfonta, L., Zhang, Z. Transforming Methanococcusjannaschii amber suppressor tRNA : tyrosyl tRNA synthetase orthogonal pair evolved in Escherichia coli for its efficient function in mammalian cells. PlosOne, 2010, Vol. 5, issue 6, e11263.
- Umeda, A., Pranav, S., Wan, D., Chen, S., Zhang, Z., Femtosecond laser--assisted optoporation for drug and gene delivery into single mammalian cells. J. Biomed. Nanotech., accepted, 2011, 7, 334-341.
- Xiang L, Moncivais K, Jiang F, Willams B, Alfonta, L, Zhang, Z.*, Crucial optimization of translational components towards efficient incorporation of unnatural amino acids into proteins in mammalian cells. PLoS One. 2013 Jul 12;8(7):e67333.
- Smolskaya S, Zhang Z.*, Alfonta L., Enhanced yield of recombinant proteins with site-specifically incorporated unnatural amino acids using a cell-free expression system. PLoS One. 2013 Jul 2;8(7):e68363.
- Zhang, Z.*, Equilibrium of sortase A dimerization on Staphylococcus aureus cell surface mediates its cell wall sorting activity-Implication towards the development of new antiinfective agents. Proceedings of Drug Discovery & Therapy World Congress, 2013, June.
- Moncivais, K., Zhang, Z.* Tetracycline Repressor-Based Mammalian Two-Hybrid Systems , in Two Hybrid Technologies: Methods in Molecular Biology, Eds. B. Sulter and E.E. Wanker, Human Press, January 5, 2012.
- Williams, B., Zhang, Z.* Reverse Protein Engineering Towards a Fluorescent Peptide, Protein Science, Vol. 23 Suppl 1, July 2014, p160.
- Zhu, J., Williams, B., Zhang, Z* Sortase A as a Tool Box for Protein and Cellular Engineering, Research in Microbiology, 2015, in revision.
- Zhu, J., Xiang, L., Jiang, F., Williams, B, Barata, J., Zhang, Z.* Equilibrium of sortaseA dimerization on Staphylococcus aureus cell surface mediates its cell wall sorting activity, J. Experimental Biology and Medicine, accepted for publication.
- Williams, B., Umeda, A., Chanthery, Y., Shimomura, E., Barata, J., Zhang, Z.* Molecular devolution: the development of a genetically encoded fluorescent peptide, Nature Biotechnology, submitted.