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Wei-Kung Wang, M.D., Sc.D.

Professor
Department of Tropical Medicine, Medical Microbiology and Pharmacology
John A. Burns School of Medicine


Phone: 808-692-1667
Office: BSB 320E
Email: wwang60 [at] yahoo.com
Curriculum Vitae

Bio

Education

1986 M.D. Medicine, National Taiwan University, Taipei, Taiwan
1995 Sc.D. Virology, Harvard School of Public Health, Boston, Massachusetts

Specialization

Molecular Virology and Viral Pathogenesis

Research Keywords: Dengue virus, envelope protein, precursor membrane protein, virus-like particles, antibody response


Research Overview

Dr. Wang’s lab has been studying virus-host interaction and disease pathogenesis of dengue virus (DENV). His lab showed that the level and rate of decline of dengue viral load and virus-containing immune complexes correlate with disease severity (Wang et al., 2003, Virology; 2006, Clin. Infect. Dis.). And his lab reported for the first time the quasispecies nature of DENV in human (Wang et al., 2002, J. Virol.) and mosquito (Lin et al., 2004, J. Virol), which provides new insight into our understanding of the evolutionary conservation of DENV.

Recently, his research focused on the antibody responses to DENV envelope (E) protein during the natural course of infection; his lab reported that the majority of anti-E antibodies is cross-reactive and recognizes highly conserved residues at the fusion loop of domain II (Lai et al., 2008, J. Virol.). These findings not only provided a molecular evidence to explain the flavivirus cross-reactivity that has been known for decades, but also have implications to our understanding our the pathogenesis of dengue and future design of subunit vaccines against DENV.

His research also focused on the functions of precursor membrane (prM)/E proteins of DENV and formation of virus-like particles (VLPs). His lab discovered the ER retention signal and critical elements of the stem-anchor region of DENV E protein. (Hsieh et al., 2008, Virology; 2010, J. Virol.), and reported that the helical domains of the stem regions of prM and E proteins are involved in both assembly and entry, two important steps of the replication cycles of DENV (Hsieh et al., 2011, Virology; Lin et al., 2011, J. Virol.), Currently, his lab is interested in identifying the stem residues highly conserved among different flaviviruses and critical for DENV replication as potential targets for future antivirals.

The current COBRE research project has three specific aims:

Specific Aim 1

  • Investigate the role of highly conserved residues in the stem region of the E protein on the entry and assembly of DENV serotype 4 (DENV4).

    • Hypothesis: Highly conserved residues in the stem are involved in entry and assembly.
    • Rationale: Mutational studies of TBEV E protein suggest the stem is involved in the assembly of VLPs. Peptide derived from the stem can block entry of DENV. Highly conserved residues at the stem are likely to be involved in such processes.
    • Experimental Plan: Site-directed mutagenesis will be carried out to replace the highly conserved stem residues in DENV4 prM/E expressing construct. Assembly will be assessed by examining VLPs production, and incorporation into VLPs containing replicon (VLPs-R). Entry will be examined by infectivity assays of VLPs-R and DENV4 infectious clone containing E mutations.

Specific Aim 2

  • Investigate the mechanisms of impairment in entry and assembly of DENV4 E mutants.

    • Hypothesis: Highly conserved residues in the stem are involved in the entry by affecting post-receptor binding step, or in the assembly by affecting prM-E heterodimerization or intracellular localization.
    • Rationale: The plausible mechanisms involved will be examined.
    • Experimental Plan: VLPs containing E mutants will be examined by binding to target cells and membrane fusion assay, and cells transfected with E mutants will be subjected to co-immunoprecipitation assay, subcellular fractionation assay, double-label immunofluorescence assay and digestion with endo H to examine intracellular localization.

Specific Aim 3

  • Investigate the role of highly conserved residues in the stem on the entry and assembly of other DENV serotypes and other flaviviruses, including WNV and JEV.

    • Hypothesis: Highly conserved residues in the stem are also involved in the entry and assembly of other flaviviruses.
    • Rationale: Since the residues identified in aim 1 are also conserved by other DENV serotypes and flaviviruses including WNV and JEV, they are likely to be involved in such processes.
    • Experimental Plan: Site-directed mutagenesis will be carried out for the residues in the prM/E expressing constructs of other DENV serotypes, WNV and JEV. Entry and assembly will be examined.

Selected Publications

Presentations & Talks

  • Analysis and identification of epitopes on dengue virus envelope protein recognized by monoclonal antibodies and polyclonal human sera by a high throughput assay. , 60th Annual Meeting of the American Society of Tropical Medicine and Hygiene, Philadelphia, Pennsylvania. , December 2011.
  • The helical domain of dengue virus membrane protein is involved in virus entry and assembly., 7th Annual Meeting of the Pacific Southwest RCE, Honolulu, Hawaii., August 2011.
  • Involvement of the stem region of dengue virus envelope protein in both virus assembly and entry. , 30th Annual Meeting of the American Society for Virology, Minneapolis, Minnesota. , July 2011.
  • Dengue virus envelope protein affects the expression and stability of precursor membrane protein. , 30th Annual Meeting of the American Society for Virology, Minneapolis, Minnesota. , July 2011.
  • Interaction between precursor membrane and envelope proteins of dengue virus, 59th Annual Meeting of the American Society of Tropical Medicine and Hygiene, Atlanta, Georgia, November 2010.
  • Epitope mapping of monoclonal antibodies against the envelope protein of dengue virus by a high throughput assay, Second International Symposium on human dengue pathogenesis and clinical aspects, Kaohsiung, Taiwan, October 2010.
  • Critical elements in the transmembrane domains of precursor membrane and envelope proteins of dengue virus for their retention and assembly in endoplasmic reticulum, 29th Annual Meeting of the American Society for Virology, Bozeman, Montana, July 2010.
  • Study of epitopes on dengue viral envelope protein recognized by Mabs and sera, Seventh Pediatric Dengue Vaccine Initiative Research Network Meeting, Santa Monica, California, June 2010.
  • Epitope study of Mabs against the envelope protein of dengue virus, Emerging Infectious Diseases 2009 and Fourth Asian Regional Dengue Research Network Meeting, Singapore, December 2009.
  • The C-terminus of the stem of dengue virus PrM protein is critical for the production of virus-like particles, Emerging Infectious Diseases 2009 and Fourth Asian Regional Dengue Research Network Meeting, Singapore, December 2009.
  • The length and non-hydrophobic residues in the transmembrane domain of dengue virus envelope protein critical for retention and assembly in endoplasmic reticulum , 58th Annual Meeting of the American Society of Tropical Medicine and Hygiene, Washington, DC, November 2009.
  • Retention and assembly of dengue virus envelope protein in endoplasmic reticulum , Second International Symposium on human dengue pathogenesis and clinical aspects, Kaohsiung, Taiwan, October 2009.
  • Antibody responses to envelope protein of dengue virus during the natural course of infection, Sixth Pediatric Dengue Vaccine Initiative Research Network Meeting, Asilomar Conference Grounds, Pacific Grove, California, June 2009.

Awards & Honors

  • Annual Excellent Article Award, Taiwan Society of Microbiology, December 2004.
  • Research Award, National Taiwan University, September 2004.
  • Travel Award, American Society of Tropical Medicine and Hygiene, 51th Annual meeting, November 2002.
  • Medical Virology Club Travel Grant Award, American Society for Virology, July 2001.
  • Research Award, National Science Council, Taiwan, June 1999.

Professional Services

  • (Oct. 2010).: Session Moderator, Third International Symposium on human dengue pathogenesis and clinical aspects. Tropical Medical Center, Kaohsiung, Taiwan .
  • (Oct. 2009).: Session Moderator, Second International Symposium on human dengue pathogenesis and clinical aspects. Tropical Medical Center, Kaohsiung, Taiwan .
  • (Oct. 2008).: Session Chair, First International Symposium on human dengue pathogenesis and clinical aspects. Tropical Medical Center, Kaohsiung, Taiwan .
  • (Nov. 2007).: Scientific Committee and Session Co-chair, Third Asian Regional Dengue Research Network Meeting, Taipei, Taiwan .
  • (March, 2008).: Session Chair, First UK-Taiwan International Networking for Young Scientists Symposium on Infection and Immunity, Taipei, Taiwan .
  • (Dec. 2010).: Abstract Review Committee, 12th RCMI International Symposium on Health Disparities, Nashville, Tennessee .
  • (Dec. 2009): Scientific Committee and Session Chair, Emerging Infectious Diseases 2009 and Fourth Asian Regional Dengue Research Network Meeting, Singapore .
  • (2000 to present): Ad Hoc Reviewer 2011: Journal of General Virology (3), PLoS Pathog (1), Clinical Infectious Diseases (1), PLoS One (1) Antiviral Research (1) 2010: Journal of Virology (1), Trends in Microbiology (1), PloS Neglected Tropical Diseases (1), Journal of General Virology (1), Clinical Infectious Diseases (1), Antiviral Research (1), Archives of Medical Research (1), Journal of Infectious Diseases and Immunology (1).

Grants

  • Grant No / Title: R01AI110769 / Mature Virus-like Particles as a New Strategy for Dengue Virus Vaccines
    Status / Agency: Awarded / NIH/NIAID
    Start Date / End Date: 01 April 2014 / 31 March 2019