Y. George Zheng, Ph.D.

Pharmaceutical and Biomedical Sciences
Professor
Graduate Coordinator

Pharmaceutical and Biomedical Sciences

Education

Postdoctoral Training Pharmacology, The Johns Hopkins University 2006

Ph.D. Chemistry, University of Miami, Florida 2002

M.S. Chemistry, Peking University, Beijing, China 1998

B.S. Chemistry, Peking University, Beijing, China 1995

Honors, Awards, and Achievements

Organizer of Southeastern Chemical Biology Symposium, April 2017

Leading Organizer, Pacifichem – Symposium on Epigenetic and Chromatin Biochemistry, December 2015

Organizer of NSF CWCS Workshop on Nucleic Acids, May 2012

Georgia State University Faculty Award for Undergraduate Research, 2010

Georgia Cancer Coalition Distinguished Scholar, 2007

William M. Keck Foundation Fellowship, The Johns Hopkins University School of Medicine, 2004—2006

Affiliations
Research Interests

Medicinal Chemistry, Drug Discovery, Organic Synthesis, Chemical Biology, Bioorganic Chemistry, Epigenetics, Histone Modification, Molecular Biology, Biochemistry, Enzymology, Biophysics, and Bioinformatics.

Dr. Zheng’s research lab works on the forefront area of chemistry, biology and medicine. We are particularly interested in addressing critical problems and challenges in the rapidly evolving field of epigenetics that describes gene expression profile changes that are irrelevant to genomic sequence. Mounting data show that epigenetic processes play pivotal roles in transforming normal cells into malignant tumors and in various other human pathologic conditions. Abnormality in epigenetic landscape presents characteristic biomarkers for disease diagnosis. The importance of epigenetic regulation in disease initiation and evolvement signifies a new flow of challenges and opportunities to disease research and pharmaceutical discovery. Therefore, identifying key chromatin regulatory factors such as histone modifying enzymes and chromatin remodeling complexes, understanding their activity, specificity and functional roles, and inventing potent and selective drug compounds embody demanding needs in today’s biology and pharmaceutical research. Our lab is innovating and applying advanced chemical and biological strategies, tools and agents to elucidate functions of epigenetic enzymes in disease mechanism and meanwhile provide new diagnostic and therapeutic regimens. The lab adopts an interdisciplinary approach, spanning and integrating organic chemistry, medicinal chemistry, bioorganic chemistry, molecular biology, biochemistry, enzymology, cellular biology, biophysics and bioinformatics, and a wide range of techniques are employed.

Current active research areas include: (1) development of potent and selective epigenetic therapies, and (2) design of chemical biology strategies and probes to interrogate protein acetylation- and methylation-regulated disease processes.

Selected Publications

Kim, S., Alsaidan, O. A., Goodwin, O., Li, Q., Sulejmani, E., Han, Z., Bai, A., Albers, T., Beharry, Z., Zheng, Y. G., Norris, J. S., Szulc, Z. M., Bielawska, A., Lebedyeva, I., Pegan, S. D. and Cai, H. (2017) Blocking Myristoylation of Src Inhibits Its Kinase Activity and Suppresses Prostate Cancer Progression. Cancer Res. 77, 6950-6962. Impact factor = 9.122

Hansen, J. N., Li, X., Zheng, Y. G., Lotta, L. T., Dedhe, A., Schor, N. F. (2017) Using Chemistry to Target Neuroblastoma. ACS Chem NeuroSci. 8, 2118-2123. Impact factor = 3.883

He, M., Han, Z., Zheng, Y. G.* (2018) Chemical Biology for Investigating the Epigenetic Functions of Lysine Acetyltransferases (KATs). Angew Chem Int Ed. 57,1162-1184. Impact factor = 11.994

Fulton, M., Zhang, J., He, M., Zheng, Y. G.* (2017) The Intricate Effects of Lysine Modifications on Arginine Methylation on the Histone H4 N-terminal Tail. Biochemistry. 56, 3539-3548. Impact factor = 2.938

Han, Z., Chou, C., Yang, X., Bartlett, M. G., Zheng, Y. G.* (2017) Profiling Cellular Substrates of Lysine Acetyltransferases GCN5 and p300 With Bioorthogonal Labeling and Click Chemistry. ACS Chem Biol. 12, 1547-1555. Impact factor = 5.00

Valerio, D. G., Xu, H., Chen, C., Hoshii, T., Eisold, M. E., Delaney, C., Cusan, M., Deshpande, A. J., Huang, C., Lujambio, A., Zheng, Y. G., Zuber, J., Pandita, T. K., Lowe S. W., Armstrong, S. A. (2017) Histone acetyltransferase activity of MOF is required for MLL-AF9 leukemogenesis. Cancer Res. 77, 1753-1762. Impact factor = 9.122

Zhang, J., Qian, K., Yan, C., He, M., Jassim, B., Ivanov, I., Zheng, Y. G.* (2017) Discovery of Decamidine as a New and Potent PRMT1 Inhibitor. MedChemComm. 8, 440–444. Impact factor = 2.608

Blazer, L. L., Li, F., Kennedy, S., Zheng, Y. G., Arrowsmith, C. H. and Vedadi, M. (2017) A Suite of Biochemical Assays for Screening RNA Methyltransferase BCDIN3D. SLAS Discov. 22, 32-39. Impact factor = 2.444

Madia, V. N., Benedetti, R., Barreca, M. L., Ngo, L., Pescatori, L., Messore, A., Pupo, G., Saccoliti, F., Valente, S., Mai, A., Scipione, L., Zheng, Y. G., Tintori, C., Botta, M., Cecchetti, V., Altucci, L., Di Santo, R. and Costi, R. (2017) Structure-Activity Relationships on Cinnamoyl Derivatives as Inhibitors of p300 Histone Acetyltransferase. ChemMedChem. In press.

Zhang, J., Qian, K., Yan, C., He, M., Jassim, B., Ivanov, I. & Zheng, Y. G. (2017) Discovery of Decamidine as a New and Potent PRMT1 Inhibitor. MedChemComm. 8, 440–444

Han, Z., Zheng, Y. G. et al. (2017) Profiling Cellular Substrates of Lysine Acetyltransferases GCN5 and p300 With Bioorthogonal Labeling and Click Chemistry. ACS Chem Biol. In press.

Blazer, L. L., Li, F., Kennedy, S., Zheng, Y. G., Arrowsmith, C. H. and Vedadi, M. (2017) A Suite of Biochemical Assays for Screening RNA Methyltransferase BCDIN3D. SLAS Discov. 22, 32-39.

Hu, H., Luo, C., Zheng, Y. G. et al. (2016) Transient Kinetics Define a Complete Kinetic Model for Protein Arginine Methyltransferase 1. J Biol Chem. 291, 26722-26738.

Li, R., Xu, J., Fu, C., Zhang, J., Zheng, Y. G. Jia, H, Liu, J. (2016) Regulation of mTORC1 by Lysosomal Calcium and Calmodulin. eLife. 5, e19360.

Eberhardt, A., Hansen, J. N., Koster, J., Lotta, L. T., Jr., Wang, S., Livingstone, E., Qian, K., Valentijn, L. J., Zheng, Y. G., Schor, N. F. and Li, X. (2016) Protein arginine methyltransferase 1 is a novel regulator of MYCN in neuroblastoma. Oncotarget. 7, 63629-63639.

Hu, H., Qian, K., Ho, M. C. and Zheng, Y. G. (2016) Small Molecule Inhibitors of Protein Arginine Methyltransferases. Expert Opin Inv Drug. 2016, 25, 335-58.

Zhang, L., Wang, R., Trans, N. T., Tang, H., Guo, A., Su, H., Placzek, W., Han, X., Hricik, T., Laha, S., Morettin, A., Abdel-Wahab, O., Côté, J.,  Levine, R., Wang, H., Raffel, G., Deng, H., Liu, Y., Zheng, Y. G.,  Luo, M., Zhao, X. (2016) Cross-talk between PRMT1-mediated methylation and ubiquitylation on RBM15 controls RNA splicing. eLife. 4, e07938.

Evich, M., Stroeva, E., Zheng, Y. G., Germann, M. W. (2016) Effect of methylation on the side-chain pKa value of arginine. Protein Sci. 25, 479-86.

Zhang, J., Zheng, Y. G. (2016) SAM/SAH Analogs as Versatile Tools for SAM-dependent Methyltransferases. ACS Chem Biol. 11, 583-97.

Qian, K., Zheng, Y. G. (2016) Current Development of Protein Arginine Methyltransferase Inhibitors. In Epi-Informatics: Discovery and Development of Small Molecule Epigenetic Drugs and Probes (Medina-Franco, J. L., ed.), Academic Press, Waltham. pp. 231-256.

Zhou, R., Xie, Y., Hu, H., Hu, G., Patel, V. S., Zhang, J., Yu, K., Huang, Y., Jiang, H., Liang, Z., Zheng, Y. G. and Luo, C. (2015) Molecular Mechanism underlying PRMT1 Dimerization for SAM Binding and Methylase Activity. J Chem Inf Model. 55, 2623-2632.

Lee, W. C., Lin, W. L., Matsui, T., Chen, E. S., Wei, T. Y., Lin, W. H., Hu, H., Zheng, Y. G., Tsai, M. D. and Ho, M. C. (2015) Protein Arginine Methyltransferase 8: Tetrameric Structure and Protein Substrate Specificity. Biochemistry. 54, 7514-7523.

Luan, Y., Blazer, L. L., Hu, H., Hajian, T., Zhang, J., Wu, H., Houliston, S., Arrowsmith, C. H., Vedadi, M. and Zheng, Y. G. (2015) Design of a fluorescent ligand targeting the S-adenosylmethionine binding site of the histone methyltransferase MLL1. Org Biomol Chem. 14, 631-638.

Han, Z., Luan, Y., Zheng, Y. G. (2015) Integration of Bioorthogonal Probes and Q-FRET for the Detection of Histone Acetyltransferase Activity. ChemBioChem. 16, 2605-2609.

Ngo, L., Wu, J., Yang, C., Zheng, Y. G. (2015) Effective Quenchers Are Required to Eliminate the Interference of Substrate―Cofactor Binding In the HAT Scintillation Proximity Assay. Assay Drug Dev Techn. 13, 210-220.

Zheng, Y. G. (2015) The State of the Art of Epigenetic Technologies. In Epigenetic Technological Applications (Zheng, Y. G., ed.), Academic Press, Waltham. p.1-18.

Luan, Y., Ngo, L., Han, Z., Wang, X., Qu, M., Zheng, Y. G. (2015) Histone Acetyltransferases: Enzymes, Assays, and Inhibitors. In Epigenetic Technological Applications (Zheng, Y. G., ed.), Academic Press, Waltham. pp.291-317.

Park, J. H., Szemesa, M., Vieiraa, G., Meleghb, Z., Malika, S., Heesomc, K. J., Von Wallwitz-Freitasa, L, Greenhoughd, A., Browna, K. W., Zheng, Y. G., Catchpoolef, D., Deeryg, M. J., Malik K. (2015) Protein arginine methyltransferase 5 is a key regulator of the MYCN oncoprotein in neuroblastoma cells. Mol Oncol. 9, 617-627.

Hu, H., Owens, E., Su, H., Yan, L., Zhao, X., Henary, M., Zheng, Y. G. (2015) Exploration of cyanine compounds as selective inhibitors of protein arginine methyltransferases: synthesis and biological evaluation. J Med Chem. 58, 1228-1243.

Qian, K. Zheng, Y. G. (2014) Labeling: Palladium brings proteins to life. Nat Chem Biol. 10, 328-330.

Yan, L., Yan, C., Su, H., Qian, K., Wofford, S., Lee, W., Zhao, X., Ho, M., Ivanov, I. and Zheng, Y. G. (2014) Diamidine Compounds for Selective Inhibition of Protein Arginine Methyltransferases. J Med Chem, 57, 2611-2622.

Yang, C., Ngo, L., Zheng, Y. G. (2014) Rational Design of Substrate-Based Multivalent Inhibitors of Histone Acetyltransferases. ChemMedChem. 9, 537-541.

Zhang, R., Li, X., Liang, Z., Zhu, K., Lu, J., Kong, X., Ouyang, S., Li, L., Zheng, Y. G., Luo, C. (2013) Theoretical insights into catalytic mechanism of protein arginine methyltransferase 1. PLoS One. 8, e72424.

Xu, J., Liu, J., Wang, A. H., Oses-Prieto, J., Makhijani, K., Pei, M., Kastuno, Y., Leilei, Y., Zheng, Y. G., Burlingame, A., Brückner, K., Derynck, R. (2013) Arginine methylation initiates BMP-induced Smad signaling. Mol Cell. 51, 5-19.

Yang, C., Mi, J., Feng, Y., Ngo, L., Gao, T., Yan, L., Zheng, Y. G. (2013) Labeling lysine acetyltransferase substrates with engineered enzymes and functionalized cofactor surrogates. J Am Chem Soc. 135, 7791-7794.

Gao, T. Yang, C., Zheng, Y. G. (2013) Comparative studies of thiol-sensitive fluorogenic probes for HAT inhibitor screening. Anal Chem Biochem. 405, 1361-1371.

Gao, T., Zheng, Y. G. (2013) The fluorescence-based acetylation assay using thiol-sensitive probes. Methods Mol Biol. 981, 229-38.

Yang, C., Wu, J., Sinha, S., Neveu, J. M., Zheng, Y. G. (2012) Autoacetylation of the MYST Lysine Acetyltransferase MOF. J Biol Chem. 287, 34917-34926.

Yang, C. Wu, J., Zheng, Y. G. (2012) Function of the Active Site Lysine Autoacetylation in Tip60 in Catalysis. PLoS ONE. 7, e32886.

Wang, J., Chen, L., Sinha, S. H., Liangb, Z., Cai, H., Muniyanf, S., Chou, Y., Yang, C., Li, K., Lin, M., Jiang, H., Zheng, Y. G., Luo, C. (2012) Pharmacophore-Based Virtual Screening and Biological Evaluation of Small Molecule Inhibitors for Histone Arginine Methyltransferases. J Med Chem. 55, 7978–7987.

Sinha, S. H., Owens, E., Feng, Y., Yang, Y., Xie, Y., Tu, Y., Henary, M., Zheng, Y. G. (2012) Synthesis and evaluation of carbocyanine dyes as PRMT inhibitors and imaging agents. Eur J Med Chem. 54, 647-659.

Ni, N., Laughlin, S., Wang, Y., Feng, Y., Zheng, Y. G. and Wang, B. (2012) Probing the general time scale question of boronic acid binding with sugars in aqueous solution at physiological pH. Bioorg Med Chem. 20, 2957-2961.

Ghizzoni, M., Wu, J., Gao T., Haisma, H. J., Dekker, F. J., Zheng, Y. G. (2012) 6-alkylsalicylates are selective Tip60 inhibitors and target the acetyl-CoA binding site. Eur J Med Chem. 47, 337–344.

Yuan, H., Rossetto, D., Mellet, H., Dang, W., Srinivasan, M. Johnson, J., Hodawadekar, S., Ding, E. C., Speicher, K.,  Abshiru, N., Perry, R., Yang, C., Wu, J., Zheng, Y. G., Speicher, D. W., Thibault, P., Verreault, A., Johnson, F. B., Berger, S. L., Sternglanz, R., McMahon, S. B., Jacques Côté, J., Marmorstein, R. (2012) MYST Protein Acetyltransferase Activity Requires Active Site Lysine Autoacetylation. EMBO J. 31, 58-70.

Wu, J., Xie, N., Zheng, Y. G. (2012) Scintillation Proximity Assay of arginine methylation. J Biomol Screen. 17, 237-244.

Li, K., Luo, C., Wang, D., Zheng, Y. G. (2012) Chemical and biochemical approaches in the study of histone methylation and demethylation. Med Res Rev. 32, 815-867.

Feng, Y., Xie, N., Jin, M., Stahley, M. R., Stivers, J. T., Zheng, Y. G. (2011) A transient kinetic analysis of PRMT1 catalysis. Biochemistry. 50, 7033–7044.

Wu, J., Wang, J., Li, M., Yang, Y., Wang, B., Zheng, Y. G. (2011) Small molecule inhibitors of histone acetyltransferase Tip60. Bioorg Chem. 39, 53-58.

Feng, Y., Wang, J., Asher, S., Hoang, L., Guardiani, C., Ivanov, I., Zheng, Y. G. (2011) Histone H4 Acetylation Differentially Modulates Arginine Methylation by an In Cis Mechanism. J Biol Chem. 286, 20323-20334.

Wu, J., Zheng, Y. G. (2010) Synthesis of H4 pantetheine adducts for histone acetyltransferase inhibition. Heterocycl Commun. 16, 231-234.

Feng, Y., Li, M., Wang, B., Zheng, Y. G. (2010) Discovery and Mechanism of a Type of new PRMT inhibitors. J Med Chem. 53, 6028-6039.

Feng, Y., Xie, N., Wu, J., Yang, C., Zheng, Y. G. (2009) Inhibitory study of protein arginine methyltransferase 1 using a fluorescent approach. Biochem Biophys Res Commun. 379, 567-572.

Wu, J., Xie, N., Wu, Z., Zhang, Y. and Zheng, Y. G. (2009) Bisubstrate Inhibitors of the MYST HATs Esa1 and Tip60. Bioorg Med Chem. 17, 1381-1386.

Xie, N., Elangwe, E. N., Asher, S. and Zheng, Y. G. (2009) A dual-mode fluorescence strategy for screening HAT modulators. Bioconjug Chem. 20, 360-366.

Zheng, Y. G., Wu, J., Chen, Z. and Goodman, M. (2008) Chemical regulation of epigenetic modifications: Opportunities for new cancer therapy. Med Res Rev. 28, 645-687.

Wu, J. and Zheng, Y. G. (2008) Fluorescent reporters of the histone acetyltransferase. Anal Biochem. 380, 106-110.

Grant Support

National Institutes of Health (NIH)

National Science Foundation (NSF)

American Heart Association (AHA)

Georgia Research Alliance (GRA)