Professor David Tscharke
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About
David Tscharke began his research career at the University of Adelaide and IMVS in Adelaide, studying interactions between the immune system and herpes simplex virus (HSV, the cause of cold sores). After gaining his PhD he worked in postdoctoral positions at Oxford University and then Imperial College London in the UK, working on projects related to viral pathogenesis and vaccine design. Following this, he moved to the US National Institutes of Health (Bethesda, MD) where he focused on understanding how the immune system recognises viruses and vaccines. He then returned to Australia, working first at QIMR in Brisbane, before starting his own lab and taking on undergraduate teaching in the former department of Biochemistry and Molecular Biology at the ANU in 2006. Since then he has received a Young Tall Poppy Award and has held an NHMRC Career Development Award and ARC Future Fellowship. In 2016 he moved his laboratory across campus to the John Curtin School of Medical Research and took up an NHMRC Senior Research Fellowship. Throughout his career he has had the benefit of working with excellent mentors, generous collaborators and brilliant students. His current research combines all the themes he has developed throughout his career, from understanding the dormant phase of infection with HSV to gaining new insight into the way our immune system recognises and responds to viruses and vaccines.
Affiliations
Research interests
- Cellular Immunology
- Virology
- Immunology
- Immunogenetics (Incl. Genetic Immunology)
Projects
- RNA-binding proteins rewire transcriptomes during immune cell differentiation., Researcher
- Quantitative studies of the presentation of viral antigens to the immune system (especially CD8+ T cells) during infection, Supervisor
- Uncovering the roles of viral and host genes in viral pathogenesis, Supervisor
- Understanding herpes simplex virus latency, Supervisor
Location
2.225
Publications
- Russell, T, Stefanovic, T & Tscharke, D 2015, 'Engineering herpes simplex viruses by infection-transfection methods including recombination site targeting by CRISPR/Cas9 nucleases', Journal of Virological Methods, vol. 213, pp. 18-25.
- Croft, N, Purcell, A & Tscharke, D 2015, 'Quantifying epitope presentation using mass spectrometry', Molecular Immunology, vol. 68, no. 2, pp. 77-80.
- Croft, N. P., D. A. de Verteuil, S. A. Smith, Y. C. Wong, R. B. Schittenhelm, D. C. Tscharke, and A. W. Purcell. 2015, 'Simultaneous quantification of viral antigen expression kinetics using data-independent (DIA) mass spectrometry', Molecular and Cellular Proteomics, vol. 14, no. 5, pp. 1361-1372.
- Flesch, I. E. A., K. L. Randall, N. A. Hollett, H. Di Law, L. A. Miosge, Y. Sontani, C. C. Goodnow, and D. C. Tscharke. 2015, 'Delayed control of herpes simplex virus infection and impaired CD4+ T-cell migration to the skin in mouse models of DOCK8 deficiency', Immunology and Cell Biology, vol. 93, no. 2015, pp. 517-521.
- Flesch, I., N. Hollett, Y.-C. Wong, B. Quinan, D. Howard, F. da Fonseca, and D. Tscharke. 2015, 'Extent of systemic spread determines CD8+ T cell immunodominance for laboratory strains, smallpox vaccines, and zoonotic isolates of vaccinia virus', Journal of Immunology, vol. 195, no. 5, pp. 2263-2272.
- Tscharke DC, Croft NP, Doherty PC & La Gruta NL. 2015, Sizing up the key determinants of the CD8+ T cell response, Nature Reviews Immunology, vol. 15, no. 11, pp. 705-716.
- Tseng, Y.-Y., F.-Y. Lin, S.-F. Cheng, D. Tscharke, S. Chulakasian, C.-C. Chou, Y.-F. Liu, W.-S. Chang, M.-L. Wong, and W.-L. Hsu. 2015, 'Functional analysis of the short isoform of orf virus protein OV20.0', Journal of Virology, vol. 89, no. 9, pp. 4966-4979.
- Trujillo JA, Croft NP, Dudek NL, Channappanavar R, Theodossis A, Webb AI, Dunstone MA, Illing PT, Butler NS, Fett C, Tscharke DC, Rossjohn J, Perlman S, and Purcell AW 2014, 'The cellular redox environment alters antigen presentation', Journal of Biological Chemistry, vol. 289, no. 40, pp. 27979-27991.
- Ma, J, Russell, T, Spelman, T, *Carbone FR, and *Tscharke DC 2014, 'Lytic Gene Expression Is Frequent in HSV-1 Latent Infection and Correlates with the Engagement of a Cell-Intrinsic Transcriptional Response', PLoS Pathogens, vol. 10, no. 7. e1004237. *Equal contribution
- Russell TA and Tscharke DC 2014, 'Strikingly poor CD8+ T-cell immunogenicity of vaccinia virus strain MVA in BALB/c mice', Immunology and Cell Biology, vol. 92, no. 5, pp. 466-469.
- Macleod BL, Bedoui S, Hor JL, Mueller SN, Russell TA, Hollett NA, Heath WR, Tscharke DC, Brooks AG, and Gebhardt T. 2014, 'Distinct APC Subtypes Drive Spatially Segregated CD4+ and CD8+ T-Cell Effector Activity during Skin Infection with HSV-1', PLoS Pathogens, vol. 10, no. 8. e1004303
- Dobson, B, Procter, D, Hollett NA, Flesch IEA, Newsome TP, and Tscharke DC 2014, 'Vaccinia virus F5 is required fornormal plaque morphology in multiple cell lines but not replication in culture or virulence in mice', Virology, vol. 456-457, pp. 145-156.
- Dobson, B & Tscharke, D 2014, 'Truncation of gene F5L partially masks rescue of vaccinia virus strain MVA growth on mammalian cells by restricting plaque size', Journal of General Virology, vol. 95, pp. 466-471.
- Quinan BR, Flesch IEA, Pinho TMG, Coelho FM, *Tscharke DC, and *da Fonseca FG. 2014, 'An intact signal peptide on dengue virus E protein enhances immunogenicity for CD8+ T cells and antibody when expressed from modified vaccinia Ankara', Vaccine, vol. 32, no. 25, pp. 2972-2979. *Equal contribution
- Mackay LK, Rahimpour A, Ma JZ, Collins N, Stock AT, Hafon M-L, Vega-Ramos J, Lauzurica P, Mueller SN, Stefanovic T, Tscharke DC, Heath WR, Inouye M, Carbone FR, and Gebhardt T. 2013, 'The developmental pathway for CD103+CD8+ tissue-resident memory T cells of skin', Nature Immunology, vol. 14, no. 12, pp. 1294-1301.
- Kerr PJ, Rogers MB, Fitch A, DePasse JV, Cattadori IM, Twaddle AC, Hudson PJ, Tscharke DC, Read AF, Holmes EC, and Ghedin E. 2013, 'Genome Scale Evolution of Myxoma Virus reveals Host-Pathogen adaptation and rapid Geographic spread', Journal of Virology, vol. 87, no. 23, pp. 12900-12915.
- Wong, Y, Smith, S & Tscharke, D 2013, 'Systemic toll-like receptor ligation and selective killing of dendritic cell subsets fail to dissect priming pathways for anti-vaccinia virus CD8+ T cells', Journal of Virology, vol. 87, no. 22, pp. 11978-11986.
- Kerr P, Rogers M, Fitch A, DePasse J, Cattadori I, Hudson P, Tscharke D, Holmes E, and Ghedin E. 2013, 'Comparative analysis of the complete genome sequence of the california msw strain of myxoma virus reveals potential host adaptations', Journal of Virology, vol. 87, no. 22, pp. 12080-12089.
- Lin, C, Flesch, I & Tscharke, D 2013, 'Immunodomination during Peripheral Vaccinia Virus Infection', PLoS Pathogens, vol. 9, no. 4, pp. e1003329
- Croft NP, Smith SA, Wong YC, Tan CT, Dudek NL, Flesch IEA, Lin LCW, *Tscharke DC, and *Purcell AW. 2013, 'Kinetics of Antigen Expression and Epitope Presentation during Virus Infection', PLoS Pathogens, vol. 9, no. 1, pp. e1003129. *Equal contribution
- Wijesundara, DK, Jackson, RJ, Tscharke, DC and RANASINGHE, C. 2013, 'IL-4 and IL-13 mediated down-regulation of CD8 expression levels can dampen anti-viral CD8+ T cell avidity following HIV-1 recombinant pox viral vaccination', Vaccine, vol. 31, no. 41, pp. 4548-4555.
- Wijesundara, D. K., Tscharke, D. C., Jackson, R. J. and RANASINGHE, C. 2013, 'Reduced Interleukin-4 Receptor alpha Expression on CD8+ T Cells Correlates with Higher Quality Anti-Viral Immunity', PLoS ONE, vol. 8, no. 1, p. e55788.
- Kerr, P, Ghedin, E, DePasse, J et al 2012, 'Evolutionary History and Attenuation of Myxoma Virus on Two Continents', PLoS Pathogens, vol. 8, no. 10, p. e1002950.
- Flesch, I, Wong, Y, Tscharke, D et al 2012, 'Linear fidelity in quantification of anti-viral CD8+ T cells', PLoS ONE, vol. 7, no. 6, p. e39533.
- Lin, C, Smith, S & Tscharke, D 2012, 'An intradermal model for vaccinia virus pathogenesis in mice', in Stuart N. Isaacs (ed.), Vaccinia Virus and Poxvirology. Methods and Protocols, Humana Press, Springer New York, pp. 147-159.
- Wong, Y, Lin, C, Rezende Melo Da Silva, C et al 2011, 'Engineering recombinant poxviruses using a compact GFP-blasticidin resistance fusion gene for selection', Journal of Virological Methods, vol. 171, no. 1, pp. 295-298.
- Melo-Silva, CR, Tscharke, DC, Lobigs, M, Koskinen, A, Wong, YC, Buller, RM, Mullbacher, M, Regner, M 2011, 'The Ectromelia Virus SPI-2 Protein Causes Lethal Mousepox by preventing NK Cell Responses', Journal of Virology. Vol. 81, No. 21, pp. 11170–11182.
- Flesch, I, Woo, W, Wang, Y et al 2010, 'Altered CD8+ T cell immunodominance after vaccinia virus infection and the naive repertoire in inbred and F1 mice', Journal of Immunology, vol. 184, no. 1, pp. 45-55.
- Moutaftsi, M, Tscharke, D, Vaughan, K et al 2010, 'Uncovering the interplay between CD8, CD4 and antibody responses to complex pathogens', Future Microbiology, vol. 5, no. 2, pp. 221-239.
- Theodoratos, A., Whittle, B., Enders, A., Tscharke, D. C., Roots, C. M., Goodnow, C. C. & Fahrer, A. M. 2010. 'Mouse strains with point mutations in TAP1 and TAP2', Immunology and Cell Biology, vol. 88, pp. 72-78.
- Yuen, T, Flesch, I, Noel, N et al 2010, 'Analysis of A47, an Immunoprevalent Protein of Vaccinia Virus, leads to a reevaluation of the total antiviral CD8+ T cell response', Journal of Virology, vol. 84, no. 19, pp. 10220-10229.
- Lutzky, V, Davis, J, Crooks, P et al 2009, 'Optimization of LMP-specific CTL expansion for potential adoptive immunotherapy in NPC patients', Immunology and Cell Biology, vol. 87, pp. 481-488.
- Wang, Y, Flesch, I & Tscharke, D 2009, 'Vaccinia Virus CD8+ T-Cell Dominance Hierarchies Cannot Be Altered by Prior Immunization with Individual Peptides', Journal of Virology, vol. 83, no. 17, pp. 9008-9012.
- Sette, A, Grey, H, Oseroff, C et al 2009, 'Definition of epitopes and antigens recognized by vaccinia specific immune responses: Their conservation in variola virus sequences, and use as a model system to study complex pathogens', Vaccine, vol. 27S, pp. G21-G26.
- Assarsson, E, Greenbaum, J, Sundstrom, M et al 2008, 'Kinetic analysis of a complete poxvirus transcriptome reveals an immediate-early class of genes', PNAS - Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 6, pp. 2140-2145.
- Tellam, J, Smith, C, Rist, M et al 2008, 'Regulation of protein translation through mRNAstructure influences MHC class I loading andT cell recognition', PNAS - Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 27, pp. 9319-9324.
- Oseroff, C, Peters, B, Pasquetto, V et al 2008, 'Dissociation between epitope hierarchy and immunoprevalence in CD8 responses to vaccinia virus Western Reserve', Journal of Immunology, vol. 180, no. 11, pp. 7193-7202.
- Haeryfar, S, Hickman, H, Irvine, K et al 2008, 'Terminal Deoxynucleotidyl Transferase Establishes and Broadens Antiviral CD8+ T Cell Immunodominance Hierarchies', Journal of Immunology, vol. 181, pp. 649-659.
- Fischer, M, Tscharke, D, Donohue, K et al 2007, 'Reduction of vector gene expression increases foreign antigen-specific CD8+ T-cell priming', Journal of General Virology, vol. 88, pp. 2378-2386.
- Moor, R, Morrison, L, Moss, D et al 2007, 'Use of CD107-based cell sorting ex vivo to enrich subdominant CD8+ T cells in culture', Immunology and Cell Biology, vol. 85, pp. 546-550.
- Tellam, J, Fogg, M, Rist, M et al 2007, 'Influence of translation efficiency of homologous viral proteins on the endogenous presentation of CD8+ T cell epitopes', Journal of Experimental Medicine, vol. 204, no. 3, pp. 525-532.
- Tscharke, D 2007, 'Adaptive immunity to vaccinia virus: revisiting an old friend', Future Virology, vol. 2, no. 2, pp. 163-172.
- Clark, R, Kenyon, J, Bartlett, N et al 2006, 'Deletion of gene A41L enhances vaccinia virus immunogenicity and vaccine efficacy', Journal of General Virology, vol. 87, pp. 29-38.
- Moutaftsi, M, Peters, B, Pasquetto, V et al 2006, 'A consensus epitope prediction approach identifies the breadth of murine TCD8+-cell responses to vaccinia virus', Nature Biotechnology, vol. 24, no. 7, pp. 817-19.
- Tscharke, D, Woo, W, Sakala, I et al 2006, 'Poxvirus CD8+ T-cell determinants and cross-reactivity in BALB/c mice', Journal of Virology, vol. 80, pp. 6318-23.
- Haeryfar, S, DiPaolo, R, Tscharke, D et al 2005, 'Regulatory T cells suppress CD8+ T cell responses induced by direct priming and cross-priming and moderate immunodominance disparities', Journal of Immunology, vol. 174, no. 6, pp. 3344-51.
- Pasquetto, V, Bui, H, Giannino, R et al 2005, 'HLA-A0201, HLA-A1101, and HLA-B0702 transgenic mice recognize numerous poxvirus determinants from a wide variety of viral gene products', Journal of Immunology, vol. 175, no. 8, pp. 5504-15.
- Tscharke, D & Suhrbier, A 2005, 'From mice to humans. Murine intelligence for human CD8+ T cell vaccine design', Expert Opinion on Biological Therapy, vol. 5, no. 2, pp. 263-71.
- Tscharke, D, Karupiah, G, Zhou, J et al 2005, 'Identification of poxvirus CD8+ T cell determinants to enable rational design and characterization of smallpox vaccines', Journal of Experimental Medicine, vol. 201, no. 1, pp. 95-104.
- Oseroff, C, Kos, F, Bui, H et al 2005, 'HLA class I-restricted responses to vaccinia recognize a broad array of proteins mainly involved in virulence and viral gene regulation', PNAS - Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 39, pp. 13980-13985.
- Smith, C, Mirza, F, Pasquetto, V et al 2005, 'Immunodominance of poxviral-specific CTL in a human trial of recombinant-modified vaccinia Ankara', Journal of Immunology, vol. 175, no. 10, pp. 8431-37.
- Norbury, C, Basta, S, Donohue, K et al 2004, 'CD8+ T Cell Cross-Priming via Transfer of Proteasome Substrates', Science, vol. 304, pp. 1318-1321.
- Tscharke, D & Yewdell, J 2003, 'T cells bite the hand that feeds them (News and Views)', Nature Medicine, vol. 9, pp. 647-48.
- Pires de Miranda, M, Reading, P, Tscharke, D et al 2002, 'The vaccinia virus kelch-like protein C2L affects calcium-independent adhesion to the extracellular matrix and inflammation in a murine intradermal model', Journal of General Virology, vol. 84, pp. 2459-71.
- Symons, J, Adams, E, Tscharke, D et al 2002, 'The vaccinia virus C12L protein inhibits mouse IL-18 and promotes virus virulence in the murine intranasal model', Journal of General Virology, vol. 83, pp. 2833-2844.
- Tscharke, D, Reading, P & Smith, G 2002, 'Dermal infection with vaccinia virus reveals roles for virus proteins not seen using other inoculation routes', Journal of General Virology, vol. 83, pp. 1977-86.
- Price, N, Tscharke, D & Smith, G 2002, 'The vaccinia virus B9R protein is a 6 kDa intracellular protein that is non-essential for virus replication and virulence', Journal of General Virology, vol. 83, pp. 873-878.
- Symons, J, Tscharke, D, Price, N et al 2002, 'A study of the vaccinia virus interferon-y receptor and its contribution to virus virulence', Journal of General Virology, vol. 83, pp. 1953-64.
- Bartlett, N, Symons, J, Tscharke, D et al 2002, 'The vaccinia virus N1L protein is an intracellular homodimer that promotes virulence', Journal of General Virology, vol. 83, pp. 1965-1976.
- Tscharke, D & Smith, G 2002, 'Notes on transient host range selection for engineering vaccinia virus strain MVA', BioTechniques, vol. 33, pp. 186-8.
- Yewdell, J & Tscharke, D 2002, 'Inside the professionals (News and Views)', BioTechniques, vol. 418, pp. 923-4.
- Gardner, J, Tscharke, D, Reading, P et al 2001, 'Vaccinia virus semaphorin A39R is a 50-55 kDa secreted glycoprotein that affects the outcome of infection in a murine intradermal model', Journal of General Virology, vol. 82, pp. 2083-2093.
- Ng, A, Tscharke, D, Reading, P et al 2001, 'The vaccinia virus A41L protein is a soluble 30 kDa glycoprotein that affects virus virulence', Journal of General Virology, vol. 82, pp. 2095-2105.
- Almazan, F, Tscharke, D & Smith, G 2001, 'The vaccinia virus superoxide dismutase-like protein (A45R) is a virion component that is nonessential for virus replication', Journal of Virology, vol. 75, pp. 7018-7029.