Division of Infectious Diseases

Ziwei Huang, PhD

Professor of Medicine

University of California, San Diego

School of Medicine

9500 Gilman Drive
Mail Code 0711
La Jolla, CA 92093-0711

Telephone: (858) 822-0333
Fax: (858) 822-5362
Email: zhuang@ucsd.edu


Background

Ziwei Huang, PhD, has over 25 years of experience in structure-based discovery of small molecular drugs, especially those for the treatment of cancer, immune and stem cell-related diseases. He has published more than 100 research papers, reviews and book chapters in the field and owned or co-owned many issued patents or pending patent applications for drug-related new technologies or products.

Recently, Dr. Huang's laboratory has developed highly promising candidate leads to promote site-specific stem cell migration. The latest technologies and discoveries from several different fields are combined through the close collaboration of internationally recognized experts in chemistry, biochemistry and biology.

Dr. Huang joined UC San Diego in 2015 from the Sanford-Burnham Medical Research Institute in La Jolla. He had been Adjunct Professor in the UC San Diego Department of Pathology from 2005 through 2011, and a Professor at the Burnham Institute for Medical Research from 2004 through 2009.

He was Professor and Chair (2009-2013) of the Department of Pharmacology, Director (2009-2013), SUNY Upstate Cancer Research Institute, Associate Vice President for Research Partnerships and International Collaborations (2011-2013), Director (2012-2013), the New York Center for Drug Discovery and Development, State University of New York (SUNY) Upstate Medical University, Syracuse, NY.

Dr. Huang received his PhD in chemistry at UC San Diego in 1993.

 

Research Interests

Dr. Huang's laboratory works on the broad area of drug design and discovery, biochemistry and pharmacology with specific interests in developing and applying computer-aided, structure-based techniques to study protein-protein and receptor-ligand interactions implicated in cancer, viral infection, immune and inflammatory disease, neurodegeneration, cardiovascular disease, and stem cell-based regenerative medicine. The overall focus is on both fundamental basic research to study and understand the pharmacological mechanism of protein-protein or receptor-ligand/inhibitor interactions and translational drug discovery research to apply such studies of biological recognition to the development of new therapeutics for treating human diseases. In recent years, he and his coworkers have conducted a number of research projects supported by extramural grants as highlighted below.

Dr. Huang is studying the structure-function relationship and mechanism in biological recognition and signal transduction of chemokine receptors and their ligands. For example, he and his coworkers are studying CXCR4 and CCR5, two principal coreceptors of HIV entry, to understand their role in HIV entry mechanism and gain more general understanding of the signaling mechanism of G protein-coupled receptors (GPCRs). They have applied a combination of chemistry, biophysics, pharmacology, and cell biology to study the structure and interaction of these GPCRs and designed novel synthetic inhibitors targeting HIV infection via these GPCR coreceptors. In addition to HIV, Dr. Huang and coworkers are interested in other infectious diseases such as hepatitis C virus (HCV) and West Nile virus (WNV) and developing new inhibitors of the infection by these viruses.

The Huang laboratory is interested in the study of proteins involved in apoptosis and angiogenesis of cancer cells. For example, Bcl-2 family and IAP family of proteins are involved in apoptosis of cancer cells. The Huang laboratory is studying the structure-function relationship of these proteins and developing new small molecules targeted to these proteins capable of triggering apoptosis of cancer cells. The Eph receptor family proteins are involved in angiogenesis of cancer cells. Dr. Huang and coworkers are investigating the pharmacology and biochemistry of Eph ligand-receptor interactions and developing new synthetic molecules (both modified peptides and non-peptidic small molecules) to probe and regulate Eph receptor functions in cancer.

Finally, the Huang laboratory has initiated new research in the area of stem cell-based therapeutic discovery. For example, by targeting the SDF-1α/CXCR4 axis which is a master regulator of both normal stem cell trafficking and cancer stem cell metastasis, Dr. Huang and coworkers are working on the discovery of novel agents that can specifically direct/promote the migration of neural stem cells toward the injury sites in the brain for regenerative medicine or blocking the metastasis of cancer stem cells for the treatment of cancer.

The central theme for all of Dr. Huang's research projects, some highlighted above, is the understanding of the pharmacological basis of protein-protein and protein-ligand interactions and translation of such basic knowledge into the discovery of new drugs. As detailed in many of his publications, he has developed and applied various techniques related to drug discovery, such as computational chemistry and structure-based drug design, synthetic medicinal chemistry, biophysical and biochemical analysis, and molecular and cellular biology.

 

Selected Publications

  1. Chang-Zhi Dong, Shaomin Tian, Won-Tak Choi, Santosh Kumar, Dongxiang Liu, Jing An, and Ziwei Huang. (2012) Critical Role in CXCR4 Signaling and Internalization of the Polypeptide Main Chain in the N-terminus of SDF-1α Probed by Novel N-Methylated Synthetically and Modularly Modified Chemokine Analogs. Biochemistry, 51:5951-7. PMID 22779681
  2. Won-Tak Choi, Srinivas Duggineni, Yan Xu, Ziwei Huang, and Jing An. (2011) Drug Discovery Research Targeting the CXC Chemokine Receptor 4 (CXCR4). Journal of Medicinal Chemistry, 55(3):977-94. PMID: 22085380
  3. Won-Tak Choi, Santhosh Kumar, Navid Madani, Xiaofeng Han, Shaomin Tian, Changzhi Dong, Dongxiang Liu, Srinivas Duggineni, Jian yuan, Joseph G. Sodroski, Ziwei Huang, Jing An. (2012) A novel synthetic bivalent ligand to probe chemokine receptor CXCR4 Dimerization and Inhibit HIV-1 Entry. Biochemistry, 51(36):7078-86. PMID 22897429
  4. Sameer P Kawatkar, Maocai Yan, Harsukh Gevariya, Mi Youn Lim, Steven Eisold, Xuejun Zhu, Ziwei Huang Z, and Jing An. (2011) Computational analysis of the structural mechanism of inhibition of chemokine receptor CXCR4 by small molecule antagonists. Experimental Biology & Medicine, 236 (7): 844-850. PMID 21697335
  5. Dongxiang Liu, Navid Madani, Ying Li, Rong Cao, Won-Tak Choi, Sameer P. Kawatkar, Mi Youn Lim, Santosh Kumar, Chang-Zhi Dong, Jun Wang, Julie D. Russell, Caroline R. Lefebure, Jing An, Scott Wilson, Yi-Gui Gao, Luke A. Pallansch, Joseph G. Sodroski, and Ziwei Huang. (2007) Crystal structure and structural mechanism of anti-HIV, D-amino acid containing SMM-chemokines.Journal of Virology, 2007, 81:11489-11498. PMID: 17686848
  6. Srinivas Duggineni, Sayantan Mitra, Roberta Noberini, Xiaofeng Han, Nan Lin, Yan Xu, Wang Tian, Jing An, Elena B Pasquale and Ziwei Huang. (2013) Design, synthesis and characterization of novel small molecular inhibitors of Ephrin-B2 binding to EphB4. Biochemical Pharmacology, 85:507–513. PMID: 23253822
  7. Srinivas Duggineni, Sayantan Mitra, Ilaria Lamberto, Xiaofeng Han, Yan Xu, Jing An, Elena B. Pasquale and Ziwei Huang. (2013) Modulating Eph receptor signaling with synthetic bivalent ligands: Design and biological characterization of novel dimeric peptides targeting the EphA2 receptor. ACS Medicinal Chemistry Letters, in press.
  8. Yongjun Mao, Nan Lin, Wang Tian, Xiaofeng Han, Xiaobing Han, Ziwei Huang, and Jing An. (2012) Design, Synthesis and Biological Evaluation of New Diaminoquinazolines as β-Catenin/Tcf4 Pathway Inhibitors. Journal of Medicinal Chemistry, 55(3):1346-59. PMID: 22229647
  9. Qi Hu, Aihua Nie, Kate Welsh, Fernando R. Pinacho Crisóstomo, Xuejun Zhu, Zhengxiang Li, Jing An, John C. Reed, Liangren Zhang, and Ziwei Huang. (2011) Novel XIAP inhibitors as probes of apoptosis in biology and medicine. Experimental Biology & Medicine, 2011, 236:247-51. PMID 21321323
  10. Roberta Noberini, Sayantan Mitra, ombretta Salvucci, Fatima Valencia, Srinivas Duggineni, Natalie Prigozhina, Ke Wei, Giovanna Tosato, Ziwei Huang and Elena B Pasquale. (2011) PEGylation potentiates the effectiveness of an antagonistic peptide that targets the EphB4 receptor with nanomolar affinity. PloS One, 6:e28611. PMID: 22194865
  11. Sayantan Mitra, Srinivas Duggineni, Mitchell Koolpe, Xuejun Zhu, Ziwei Huang and Elena B.Pasquale. (2010) Structure-Activity Relationship Analysis of Peptides Targeting the EphA2 Receptor. Biochemistry, 49, 6687-6695. PMID: 20677833
  12. Dongmei Wu, Yuhong Pang, Yuehai Ke, Jianxiu Yu, zhao He, Luts Tautz, Tomas Mustelin, Sheng Ding, Ziwei Huang and Geng-sheng Feng. A conserved mechanism for control of human and mouse embryonic stem cell pluripotency and differentiation by shp2 tyrosine phosphatase. (2009) PLoS ONE, 4:e4914. PMID: 19290061
  13. Andreas Krieg, Ricardo G. Correa, Jason B. Garrison, Gaëlle Le Negrate, Kate Welsh, Ziwei Huang, Wolfram T. Knoefel, and John C. Reed. (2009) XIAP mediates NOD signaling via interaction with RIP2. Proceedings of the National Academy of Sciences USA, 2009, 106:14524-9. PMID: 19667203
  14. Won-Tak Choi, Marcus Kaul, Krishna M Kumar, Jun Wang, Changzhi Dong, Jing An, Stuart A Lipton, Ziwei Huang. (2007) Neuronal apoptotic signaling pathways probed and intervened by chemically engineered SMM-chemokines. Journal of Biological Chemistry, 282: 7154-7163. PMID 17218311
  15. Won-Tak Choi, Shaomin Tian, Chang-Zhi Dong, Santhosh Kumar, Dongxiang Liu, Navid Madani, Jing An, Joseph G. Sodroski and Ziwei Huang. Unique ligand binding sites on CXCR4 probed by a chemical biology approach: implications for the design of selective human immunodeficiency virus type 1 inhibitors. Journal of Virology, 2005, 79: 15398-15404. PMID: 16306611