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Tung T. Hoang, Ph.D.

Professor
Department of Microbiology
College of Natural Sciences


Phone: 808-956-3522
Office: Snyder Hall 308
Email: tongh [at] hawaii.edu
External Homepage

Bio

Education
1994 B.Sc. Biochemistry, University of Calgary, Calgary, Alberta, Canada
1996 M.Sc. Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada
2000 Ph.D. Microbiology, Colorado State University, Fort Collins, Colorado

Specialization

Bacterial Genetics and Molecular Pathogenesis

Research Keywords: Burkholderia pseudomallei, transcriptome analysis, intracellular pathogenesis


Research Overview

For the past few years, I have been fascinated and passionate about the pathophysiology of B. pseudomallei, which causes a disease called melioidosis. Born and raised in Vietnam during the war and running around in rice fields where the bacterium is found, I never realized the importance of this bacterium until recently. My lab has worked with B. pseudomallei for the past three years engineering and publishing several molecular genetic tools for the scientific community. The lab currently researches the molecular pathogenesis of B. pseudomallei during its infection within host-cells. Our hypothesis is that B. pseudomallei, as it encounters and senses uniquely different intracellular environments and performs sequential steps in the infection process, will undergo differential gene expression at each stage of intracellular cycle. We pioneered and studied global transcriptional profiling of single B. pseudomallei cells as it transit through the host cell, which we cumulatively named a “transitome.” Our goal is to more clearly identify the genes, and hence the proteins, required for eukaryotic hosts’ cellular infection in each spatially defined infectious stage (vesicle, cytoplasm, and membrane protrusion). Ultimately, understanding the function of these virulence genes and mechanisms of infection and disease at the molecular level will aid in rational drug and vaccine design. My short journey of escaping Vietnam at the age of 10 to being a refugee in Thailand, immigrated to Canada with not a word of English, obtained my PhD at Colorado State University and now back to studying a potential bioterrorism agent found in rice fields throughout Southeast Asia has come full circle, with full of passion and enjoyment for this research to help people inflicted with melioidosis.

This current COBRE research project has two specific aims:

Specific Aim 1

  • Identify and assign in vivo expressed B. pseudomallei genes on a temporal scale.
    • Hypothesis: Once whole macrophage culture infection initiates, differential gene expression identified at various times will reflect genes required for different stages of cellular infection.
    • Rationale: Identifying genes differentially expressed on a temporal scale during host-cell infection will yield insight into the pathogenic mechanisms of B. pseudomallei.
    • Experimental Plan: We will utilize the available B. pseudomallei whole genome array from the NIAID Pathogen Functional Resource Center at the J. Craig Venter Institute. We will infect the mouse macrophage cell line RAW264.7 with B. pseudomallei strain K96243, kill extracellular bacteria, and bacterial RNA will be isolated after lysis of macrophage culture at various times for microarray and real-time RT-PCR studies.

Specific Aim 2

  • Identify essential B. pseudomallei genes for macrophage infection and assign the expression of these genes on a spatiotemporal scale.
    • Hypothesis: Only a subset of in vivo expressed genes in aim 1 are essential for the progression of cellular infections.
    • Rationale: Since the majority of gene expressed in aim 1 may not be essential for intracellular infection, the negative selection strategy in aim 2 will identify genes directly essential for the intracellular infection process.
    • Experimental Plan: A high-throughput signature-tagged mutagenesis approach will be utilized with four fluorescent protein tags (red, yellow, green, and cyan) each individually located on a transposon. Each well of a 96-well plate will contain four different colored bacteria (i.e., 4 different transposon mutants), which will be infected into a single well of a 96-well plate of cultured macrophage. Hence, each 96-well plate of cell culture will allow screening of 384 transposon mutants. Screening will be performed to detect the lack of any four types of fluorescent plaques in each well. We will confirm expression of these genes by live cell imaging and real-time RT-PCR.

Selected Publications

Presentations & Talks

  • Hoang, T.T. 2011. Natural transformation and DNA uptake systems of Burkholderia spp., National Regional Centers of Excellence Meeting invited talk, Denver, CO, April 2011.
  • Hoang, T.T. 2011. The transitome of Burkholderia pseudomallei host-cell infection reveals dynamic gene expression, the Pacific Southwest Regional Center of Excellence sponsored Burkholderia Workshop, invited talk presented at UCLA, CA, March 2011.
  • Norris, M.H., Kang, Y., Zarzycki-Siek, J., Khan, A.G., and T.T. Hoang. 2010. Efforts in identification of Burkholderia genes contributing to natural competency and DNA degradation, poster number P67, presented at the 6th World Melioidosis Congress, Townsville, Australia, December 2010.
  • Kang, Y., Norris, M.H., Sun, Z., Neirman, W.C., and T.T. Hoang. 2010. Single-cell microarray reveals spatial gene expression of Bukholderia pseudomallei during macrophage infection, poster number P100, presented at the 6th World Melioidosis Congress, Townsville, Australia, December 2010.
  • Hoang, T. T. 2010. Analysis of Burkholderia pseudomallei Genes Expressed in Defined Host-Cell Infectious Stages, The Pacific Southwest Regional Center of Excellence 6th Annual Meeting, invited talk at Stanford University, July 2010.
  • Hoang, T. T. 2010. Current Pioneering Research on the Pathophysiology of Pseudomonas aeruginosa and Burkholderia pseudomallei, invited talk by the Department of Microbiology, Immunology and Pathology at Colorado State University, June 2010.
  • Kang, Y., Norris, M.H., Zarzycki-Siek, J., and Hoang T.T. 2010. Lambda red recombineering system for naturally transformable Burkholderia thailandensis and Burkholderia pseudomallei, poster number F-27, presented at the Banff Conference on Infectious Diseases, Banff, Alberta, Canada, May 2010.
  • Kang, Y., Zarzycki-Siek, J., Walton, C.B., Norris, M.H., and Hoang, T.T. 2010. Multiple FadD acyl-CoA synthetases contribute to differential fatty acid degradation and virulence in Pseudomonas aeruginosa, poster number R-20, presented at the Banff Conference on Infectious Diseases, Banff, Alberta, Canada, May 2010.
  • Norris, M.H., Kang, Y., Propst, K., Dow, S., Schweizer, H., and Hoang, T.T. 2010. The Burkholderia pseudomallei asd mutant exhibits attenuated intracellular infectivity and imparts protection against acute inhalation melioidosis, poster number F-18, presented at the Banff Conference on Infectious Diseases, Banff, Alberta, Canada, May 2010.
  • Norris, M.H., Kang, Y., Lu, D., Wilcox, B.A., and T.T. Hoang. 2009. Glyphosate Resistance as a novel select-agent-compliant non-antibiotic marker: chromosomal mutagenesis of the essential Burkholderi pseudomallei asd and dapB genes, presented at the European Melioidosis Network Meeting, London, United Kingdom, September 2009.
  • Hoang, T.T. 2009. Non-antibiotic resistance markers and selection strategies in Burkholderia pseudomallei and Brucella spp, invited talk by the National Institute of Health, presented in Bethesda, MD, May 2009.

Grants

  • Grant No / Title: R21AI123913 / Functional Characterization of Essential Burkholderia pseudomallei Virulence Regulators
    Status / Agency: Awarded / NIH/NIAID
    Start Date / End Date: 10 March 2016 / 28 February 2018
  • Grant No / Title: R01GM103580 / Functional Genomics of Single- and Mixed-Species Biofilms in Spatiotemporal Scale
    Status / Agency: Awarded / NIH/NIGMS
    Start Date / End Date: 01 September 2013 / 30 June 2017