Qinghua Wang, Ph.D.
Department of Biochemistry and Molecular Biology
Education and Awards
- Ph.D., University of Cambridge (Professor Alan R. Fersht)
- Postdoctoral Fellow, Harvard University (Professors Don C. Wiley and Stephen C. Harrison)
- British Overseas Research Student (ORS) Awards, United Kingdom
- Postdoctoral Fellowship, The Irvington Institute for Immunological Research
- American Heart Association Beginning Grant-In-Aid Award
Epigenetic Regulation in Embryonic Stem Cells and Cancer Cells
Polycomb group proteins (PcGs) and Trithorax group proteins (TrxG) are evolutionarily conserved regulatory factors that regulate directly the expression of hundreds of genes involved in differentiation, development, cell fate decisions, stem cell self renewal, X-inactivation in females and genomic imprinting. Mutations of these proteins are implicated in defects in stem cell fates and their abnormal levels show good correlation with the severity and invasiveness of at least 11 cancer types including prostate cancer and breast cancer. Our laboratory is combining bioinformatics, biochemistry, biophysics and structural biology approaches to elucidate the molecular mechanisms of PcG and TrxG-mediated epigenetic regulation in embryonic stem cells and cancer cells. Ultimately, the insights gained from these structural and functional studies are expected to aid in the development of therapeutic agents for clinical intervention.
Actin Cytoskeleton in Signal Transduction
Actin is the most abundant protein in eukaryotic cells. It exists primarily as monomers (G-actin) bound by G-actin binding proteins that prevent spontaneous nucleation of new actin filaments, making nucleation the rate-limiting step in forming filamentous actin (F-actin). In response to cellular signals, specific actin nucleators initiate actin polymerization in a tight temporally and spatially controlled manner, which regulates many fundamental cellular processes including cellular motility, cell shape and polarity determination, and embryonic development. Understanding the de novo actin nucleation in response to stimuli lies in the core of modern biology. Our laboratory is combining bioinformatics, biochemistry and structural biology tools to investigate the molecular mechanisms of actin cytoskeleton in signal transduction.
Mechanisms of Influenza Virus Infection
Influenza virus is a negative-stranded RNA virus belonging to orthomyxoviridae family. Infections caused by influenza A and B viruses remain a major source of human morbidity and mortality worldwide, due to naturally evolving strains and to their potential use as man-made bio-weapons by terrorists. They both have a major surface glycoprotein HA that are responsible for binding to cell-surface receptors and for entering into host cells for replication. We are investigating the structures and functions of influenza A and B virus HAs. These include influenza A virus H1N1, H3N2, H5N1 and influenza B virus. Development of anti-influenza inhibitors is also underway.
- Qinghua Wang, Ashley M. Buckle, Nicholas W. Foster, Christopher M. Johnson & Alan R. Fersht. (1999). Design of highly stable functional GroEL minichaperones. Protein Science 8: 2186-2193.
- Qinghua Wang, Ashley M. Buckle & Alan R. Fersht. (2000). Stabilization of GroEL minichaperones by core and surface mutations. J. Mol. Biol. 298:917-926.
- Qinghua Wang, Ashley M. Buckle, A.M. & Alan R. Fersht. (2000). Information on GroEL-polypeptide interactions from minichaperone crystal packing. J. Mol. Biol. 304: 873-881.
- Yinghao Wu, Mingzhi Chen, Mingyang Lu, Qinghua Wang and Jianpeng Ma (2005). Determining Protein Topology from Skeletons of Secondary Structures. J. Mol. Biol. 350:571-586.
- Yinghao Wu, Xia Tian, Mingyang Lu, Mingzhi Chen, Qinghua Wang and Jianpeng Ma (2005). Folding of Small Helical Proteins Assisted by Small Angle X-ray Scattering Profiles. Structure 13:1587-1597.
- Billy K. Poon, Xiaorui Chen, Mingyang Lu, Nand K. Vyas, Florante A. Quiocho, Qinghua Wang and Jianpeng Ma (2007). Normal Mode Refinement of Anisotropic Thermal Parameters for A Supramolecular Complexe at 3.42-Å Crystallographic Resolution. Proc. Natl. Acad. Sci. USA. 104:7869-7874.
- Xiaorui Chen, Billy K. Poon, Athanasios Dousis, Qinghua Wang and Jianpeng Ma (2007). Normal Mode Refinement of Anisotropic Thermal Parameters for Potassium Channel KcsA at 3.2-Å Crystallographic Resolution. Structure 15:955-962.
- Feng Cheng, Qinghua Wang, Mingzhi Chen, Florante A. Quiocho and Jianpeng Ma (2007). Molecular Docking Study of the Interactions between the Thioesterase Domain of Human Fatty Acid Synthase and Its Ligands. Proteins: Structure, Function, and Bioinfo. 70:1228-1234.
- Qinghua Wang, Xia Tian, Xiaorui Chen and Jianpeng Ma (2007). Structural Basis for Receptor Specificity of Influenza B Virus Hemagglutinin. Proc. Natl. Acad. Sci. USA. 104:16874-16879.
- Qinghua Wang, Feng Cheng, Mingyang Lu, Xia Tian and Jianpeng Ma (2008). Crystal Structure of Unliganded Influenza B Virus Hemagglutinin. J. Virol. 82:3011-3020.
- Jun Shen, Brian D. Kirk, Jianpeng Ma and Qinghua Wang (2009). Diversifying Selective Pressure on Influenza B Virus Hemagglutinin. J. Med. Virol. 81:114-124.
- Xiaorui Chen, Mingyang Lu, Billy K. Poon, Qinghua Wang and Jianpeng Ma (2009). Structural Improvement of Unliganded Simian Immunodeficiency Virus gp120 Core by Normal-mode-based X-ray Crystallographic Refinement. Acta Cryst. D65. 339-347.
- Fengyun Ni, Billy K. Poon, Qinghua Wang and Jianpeng Ma (2009). Application of Normal-mode Refinement to X-ray Crystal Structures at Lower-resolution Limit. Acta Cryst. D65: 633-643.
- Jun Shen, Jianpeng Ma and Qinghua Wang (2009). Evolutionary Trends of A(H1N1) Influenza Virus Hemagglutinin Since 1918. PLoS One. 4(11):e7789.
- Qinghua Wang (2010). Influenza Antigenic Drift: What Is the Driving Force? Cell Science Reviews 6(3): 1-8.
- Xiaorui Chen, Qinghua Wang, Fengyun Ni and Jianpeng Ma (2010). Structure of the full-length Shaker potassium channel Kv1.2 by normal-mode-based X-ray crystallographic refinement. Proc Natl Acad Sci U S A. 107:11352-7.
- Qinghua Wang. Influenza Type B Virus Hemagglutinin: Antigenicity, Receptor Binding and Membrane Fusion, pp.29~52, in Influenza: Molecular Virology, Wang, Q. and Tao Y.J., Eds, Horizon Scientific Press (February 2010).
- Qinghua Wang and Yizhi J. Tao. Influenza: Molecular Virology, Horizon Scientific Press (2010).
- Alan R. Fersht and Qinghua Wang. The Selected Papers of Sir Alan Fersht: Development of Protein Engineering, Imperial College Press (2010).