Zhiqiang An, Ph.D.
Professor, Texas Therapeutics InstituteZhiqiang.An@uth.tmc.edu
Dr. Zhiqiang An joined the University of Texas Health Science Center at Houston in 2009 after more than 15 years in the biotechnology and pharmaceutical industry. He is appointed Professor of Molecular Medicine, the Robert A. Welch Distinguished University Chair in Chemistry, and Director of the Texas Therapeutics Institute (TTI) at the Brown Foundation Institute of Molecular Medicine. TTI was established in 2010 with funding from the Texas Emerging Technology Fund, The University of Texas System, and The UT Health Science Center at Houston for the discovery and development of therapeutic agents and diagnostic tools. TTI research is funded by competitive grants from federal and state agencies and private foundations such as NIH, CPRIT, ETF, UT System Star awards, and the Welch Foundation. More importantly, TTI has established major collaborations with industry partners on a variety of drug discovery projects. Previously, he served as Chief Scientific Officer at Epitomics, Inc. and was Director of the Biologics Research at Merck Research Laboratories. He started his biotech/pharmaceutical career at Millennium Pharmaceuticals where he worked in the field of biocombinatorial natural products drug discovery using microbial molecular genetics and engineering approaches. Dr. An received his Ph.D. degree from the University of Kentucky, Lexington, and his postdoctoral training at the University of Wisconsin-Madison.
Dr. An’s group focuses on the discovery and development of therapeutic antibodies and antibiotics against human diseases including cancer and infectious diseases. Currently, we have five major research areas. 1) cancer drug resistance mechanisms in the human epidermal growth factor receptor (HER/ErbB) signaling pathways using monoclonal antibodies as platform technology; 2) the interactions between proteases and anti-tumor antibodies in the tumor microenvironment to delineate the roles of proteases play in tumor resistance to antibody immune therapies; 3) biomarkers for therapeutic monoclonal antibodies targeting the HER/ErbB signaling pathways; 4) high throughput technologies for cloning and characterization of antibodies from animals and humans in response to experimental vaccines, and 5) Pnemocandin biosynthesis and biocombinatorial chemistry approach for natural products drug discovery. In addition to the research projects, Dr. An’s team has established a comprehensive antibody drug discovery platform with a focus on antibody lead optimization technologies such as antibody phage display, deep sequencing of antibody encoding genes from individual antibody expressing B cells, affinity maturation and humanization.
Selected peer-reviewed publications
- Qun Yue, Li Chen, Xiaoling Zhang, Kuan Li, Jingzu Sun, Xingzhong Liu, Zhiqiang An, Gerald F. Bills. 2015. Evolution of chemical 1 diversity in the echinocandin lipopeptide antifungal metabolites. Eukaryotic Cell 14(7):698-718.
- Qun Yue, Li Chen, Yan Li, Gerald F Bills, Xinyu Zhang, Meichun Xiang, Shaojie Li, Yongsheng Che, Chengshu Wang, Xuemei Niu, Zhiqiang An, and Xingzhong Liu. 2015. Functional operons in secondary metabolic gene clusters in Glarea lozoyensis (Fungi, Ascomycota, Leotiomycetes). mBio 6(3) e00703-15.
- Weixu Meng, Leike Li, Wei Xiong, Xuejun Fan, Hui Deng, Andrew J Bett, Zhifeng Chen, Aimin Tang, Kara S. Cox, Joseph G. Joyce, Daniel C. Freed, Elizabeth Thoryk, Tong-Ming Fu, Danilo R. Casimiro, Ningyan Zhang, Kalpit Vora, Zhiqiang An. 2015. Efficient generation of monoclonal antibodies from single rhesus macaque antibody secreting cells. mAbs 7(4): 707--718;
- Yan Li; Li Chen, Qun Yue, Xing-Zhong Liu, Zhiqiang An, and Gerald Bills. 2015. Genetic Manipulation of the Pneumocandin Biosynthetic Pathway for Generation of Analogues and Evaluation of Their Antifungal Activity. ACS Chemical Biology Apr 23. [Epub ahead of print].
- Yun Shi, Xuejun Fan, Hui Deng, Randall Brezski, Michael Rycyzyn, Robert Jordan, William Strohl, Quanming Zou, Ningyan Zhang and Zhiqiang An. 2015. Trastuzumab triggers phagocytic killing of high HER2 cancer cells by interaction with FcγRIV on immune cells. Journal of Immunology 194:4379-4386.
- Xuejun Fan, Randall J. Brezski, Hui Deng, Pooja Dhupkar, Yun Shi, Anneliese Gonzalez, Songlin Zhang, Michael Rycyzyn, William R. Strohl, Dr. Robert E. Jordan, Ningyan Zhang, and Zhiqiang An. 2015. A novel therapeutic strategy to rescue the immune effector function of proteolytically-inactivated cancer therapeutic antibodies. Molecular Cancer Therapeutics 14(3): 681-691.
- Li Chen, Qun Yue, Yan Li, Xuemei Niu, Dr. Meichun Xiang, Wenzhao Wang, Gerald F Bills, Xingzhong Liu, and Zhiqiang An. 2015. Engineering of Glarea lozoyensis for the exclusive production of the pneumocandin B0 precursor of the antifungal drug caspofungin acetate. Applied and Environmental Microbiology 81(5):1550-1558.
- Xing Gong, Jing Yi, Kendra Carmon, Christine Crumbley, Wei Xiong, Anthony Thomas, Xuejun Fan, Zhiqiang An, Jeffrey Chang, and Qingyun Liu. 2014. Aberrant RSPO3-LGR4 signaling in Keap1-deficient lung adenocarcinomas promotes tumor aggressiveness. Oncogene 2014 Dec 22. doi: 10.1038/onc.2014.417. [Epub ahead of print]
- Xin Wang, Guo-Hong Li, Cheng-Gang Zou, Xing-Lai Ji, Tong Liu, Pei-Ji Zhao, Lian-Ming Liang, Jian-Ping Xu, Zhi-Qiang An, Xi Zheng, Yue-Ke Qin, Meng-Qing Tian, You-Yao Xu,Yi-Cheng Ma, Ze-Fen Yu, Xiao-Wei Huang, Shu-Qun Liu, Xue-Mei Niu, Jin-Kui Yang, Ying Huang and Ke-Qin Zhang. 2014. Bacteria can mobilize nematode-trapping fungi to kill nematodes. Nature Communications 2014 Dec 16;5:5776. doi: 10.1038/ncomms6776.
- Min You, Lu Xin,Yi Yang, Xiao Zhang, Yingwei Chen, Hai Yu, Shaowei Li, Jun Zhang, Zhiqiang An, Wenxin Luo, Ningshao Xia. 2014. Investigation of a special neutralizing epitope of HEV E2s. Protein and Cell 2014 Dec;5(12):950-3. doi: 10.1007/s13238-014-0115-3.
- Kalpana Mujoo, Byung-Kwon Choi, Zhao Huang, Ningyan Zhang and Zhiqiang An. 2014. Regulation of ERBB3/HER3 signaling in cancer. Oncotarget 2014 Nov 15;5(21):10222-36.
- Yongjie Zhang, Shu Zhang, Yuling Li, Shaoli Ma, Chengshu Wang, Meichun Xiang, Xin Liu, Zhiqiang An, Jianping Xu and Xingzhong Liu. 2014. Phylogeography and evolution of a fungal–insect association on the Tibetan Plateau. Molecular Ecology (2014) 23, 5337–5355.
- Gerald Bills, Yan Li, Li Chen, Qun Yue, Xue-Mei Niu, and Zhiqiang An. 2014. New insights into the echinocandins and other fungal non-ribosomal peptides and peptaibiotics. Natural Product Reports 31:1348-1375.
- Xuemei Niu, Li Chen, Qun Yue, Baile Wang, Junxian Zhang, Chunyan Zhu, Keqin Zhang, Gerald F. Bills, and Zhiqiang An. 2014 Characterization of thermolide biosynthetic genes and a new thermolide from sister thermophilic fungi. Org Lett 16 (14), pp 3744–3747.
- Kai Sun, Jiyoung Park, William L. Holland, Olga Gupta, Pernille Landrock Auerbach, Ningyan Zhang, Roberta Goncalves Marangoni, John Varga, Thorkil Plough, Zhiqiang Anand Philipp E. Scherer. 2014. Endotrophin Triggers Adipose Tissue Fibrosis, Inflammation and Metabolic Dysfunction. Nature Communications (2014 Mar 19;5:3485. doi: 10.1038/ncomms4485).
- Zhao Huang, Byung-Kwon Choi, Kalpana Mujoo, Xuejun Fan, Ming Fa, Seema Mukherjee, Norah Owiti, Ningyan Zhang, and Zhiqiang An. 2014. The E3 ubiquitin Ligase NEDD4 Negatively Regulates HER3/ErbB3 Level and Signaling. Oncogene(2014 Mar 24. doi: 10.1038/onc.2014.56).
- Yun Shi, Xuejun Fan, Weixu Meng, Hui Deng, and Ningyan Zhang, and Zhiqiang An. 2014. Engagement of immune effector cells by trastuzumab induces HER2 downregulation in cancer cells through STAT1 activation. Brest Cancer Research16(2):R33.
- Lina Wang Dunne, Zhao Huang, Weixu Meng, Xuejun Fan, Ningyan Zhang, Qixu Zhang, Zhiqiang An. 2014. Human decellularized adipose tissue scaffold as a model for breast cancer cell growth and drug treatments. Biomaterials 35(18):4940-9.
- Daniel C. Freed, Qi Tang, Aimin Tang, Fengsheng Li, Xi He, Zhao Huang, Weixu Meng, Lin Xia, Adam C. Finnefrock, Amy S. Espeseth, Danilo R. Casimiro, Ningyan Zhang, John W. Shiver, Dai Wang, Zhiqiang An, Tong-Ming Fu. 2013. A glycoprotein H complex is the primary target for potent neutralization by an experimental human cytomegalovirus vaccine. Proc. Natl. Acad. Sci. USA110(51):E4997-E5005.
- L. Chen, Q. Yue, X. Zhang, M. Xiang, C. Wang, S. Li, Y. Che, F. J. Ortiz-López, G. F Bills, X. Liu and Z. An. 2013. Genomics-driven discovery of the pneumocandin biosynthetic gene cluster in the fungus Glarea lozoyensis. BMC Genomics14:339 doi:10.1186/1471-2164-14-339.
- N. T. Redpath, Y. Xu, N. J. Wilson, A. E. Andrews, L. J. Fabri, M. Baca, H. Braley, P. Lu, C. Ireland, R. E. Ernst, A. Woods, G. Forrest, Z. An, et al. 2013. Production of a human neutralizing monoclonal antibody and its crystal structure in complex with the ectodomain 3 of the interleukin-13 receptor α1. Biochemical Journal. 451:165-175.
- N. Zhang, M. E. Klegerman, H. Deng, Y. Shi, E. Golunski, Z. An. 2013. Trastuzumab-doxorubicin conjugate provides enhanced anti-cancer potency and reduced cardiotoxicity. Journal of Cancer Therapy. 4:308-322.
- Fan X, Brezski RJ, Fa M, Deng H, Oberholtzer A, Gonzalez A, Dubinsky WP, Strohl WR, Jordan RE, Zhang N, An Z. 2012. A single proteolytic cleavage within the lower hinge of trastuzumab reduces immune effector function and in vivo efficacy. Breast Cancer Res 14(4):R116.
- Byung-Kwon Choi, Xuejun Fan, Hui Deng, Ningyan Zhang, Zhiqiang An. 2012. ERBB3 (HER3) is a key sensor in the regulation of ERBB-mediated signaling in both low and high ERBB2 (HER2) expressing cancer cells. Cancer Medicine1(1):28-38.
- Ence Yanga, Lingling Xua, Ying Yang, Xinyu Zhang, Meichun Xiang, Chengshu Wang, Zhiqiang An,and Xingzhong Liu. 2012. Origin and evolution of carnivorism in the Ascomycota (fungi). PNAS 109 (2): 10960-10965.
- Glantschnig H, Scott K, Hampton R, Wei N, McCracken P, Nantermet P, Zhao J, Vitelli S, Huang L, Haytko P, Lu P, Fisher J, Sandhu P, Cook J, Williams D, Strohl W, Flores O, Kimmel D, Wang F, Z. An. 2011. A rate-limiting role for DKK1 in bone formation and the remediation of bone loss in mouse and primate models of postmenopausal osteoporosis by an experimental therapeutic antibody. J Pharmacol Exp Ther. 338(2):568-578.
- Q. Niu, X. Huang, L. Zhang, J. Xu, D. Yang, K. Wei, X. Niu, Z. An, J. W. Bennett, C. Zou, J. Yang, and K-Q Zhang. 2010. A Trojan horse mechanism of bacterial pathogenesis against nematodes. Proc. Natl. Acad. Sci. USA 107:16631-16636.
- Y. Yu, P. Lee, Y. Ke, Y. Zhang, Q. Yu, J. Lee, M. Li, J. Song, J. Chen, J. Dai, F. J. R. D. Couto, Z. An, W. Zhu, and G. Yu. 2010. A humanized anti-VEGF rabbit monoclonal antibody inhibits angiogenesis and blocks tumor growth in xenograft models.Plos One 5(2):e9072 (1-12).
- Z. An, G. Forrest, R. Moore, M. Cukan, P. Haytko, L. Huang, S. Vitelli, J. Z. Zhao, P. Lu, J. Hua, C. R. Gibson, B. Harvey, D. Montgomery, D. Zaller, F. Wang, and W. R. Strohl. 2009. IgG2M4, an engineered antibody isotype with reduced Fc function. mAbs1(6):572 - 579.
- Montgomery, D. L., Y-J. Wang, R. Hrin, M. Luftig, B. Su, M. D. Miller, F. Wang, P. Haytko, L. Huang, S. Vitelli, J. Condra, X. Liu, R. Hampton, A. Carfi, A. Pessi, E. Bianchi, A. Finnefrock, J. Joyce, D. Lowe, R. Geleziunas, D. Bramhill, V. M. King, W. Strohl, Z. An. 2009. Affinity maturation and characterization of a human monoclonal antibody against HIV-1 gp41. mAbs1(5):462-474.
- Yang, Y., E. Yang, Z. Anand X. Liu. 2007. Evolution of nematode-trapping cells of predatory fungi of the Orbiliaceae (Ascomycotina): evidence from ribosomal DNA and multiprotein nucleotide sequences. Proc. Natl. Acad. Sci. USA 104:8379-8384.
- D. M. Miller, R. Geleziunas, E. Bianchi, S. Lennard, R. Hrin, H. Zhang, M. Lu, Z. An, P. Ingallinella, M. Finotto, M. Mattu, A. Finnefrock, D. Bramhill, J. Cook, D. Eckert, R. Hampton, M. Patel, S. Jarantow, J. Joyce, G. Ciliberto, R. Cortese, P. Lu, W. Strohl, W. Schleif, M. McElhaugh, S. Lane, C. Lloyd, D. Lowe, J. Osbourn, T. Vaughan, E. Emini, G. Barbato, P. S. Kim, D. J. Hazuda, J. Shiver, and A. Pessi. 2005. A human monoclonal antibody neutralizes diverse HIV-1 isolates by binding to a critical gp41 epitope. Proc. Natl. Acad. Sci. USA102(41):14759-64.
- An, Z. Q., Q. Zhao, J. McEvoy,W. M. Yuan, J. L. Markley, and S. A. Leong. 1997. The second finger of Urbs1 is required for iron-mediated repression of sid1of Ustilago maydis. Proc. Natl. Acad. Sci. USA 94:5882-5887.
- An, Z. Q., B. Mei, W. M. Yuan, and S. A. Leong. 1997. The distal GATA sequences of the sid1 promoter of Ustilago maydis mediate iron repression and interact directly with Urbs1, a transcription repressor and a member of the GATA family of transcription factors. The EMBO Journal 16:1742-1750.
Z. An. Therapeutic Monoclonal Antibodies: from Bench to Clinic, Editor, John Wiley and Sons, p889, Hoboken, New Jersey (October, 2009).
Z. An. 2005. Handbook of Industrial Mycology, Editor, Marcel Dekker, p763, New York, NY.