Profiles

Guna Karupiah

UTAS Home Associate Professor Guna Karupiah

Guna Karupiah

Associate Professor of Biomedicine

Room 241Hobart CBD Campuses

+61 6226 2658 (phone)

Guna.Karupiah@utas.edu.au

If you, or someone you love, seek treatment for influenza or viral pneumonia more than 48 hours after the onset of symptoms, no specific cure is currently available. Sadly, this reality will mean death for many previously healthy people, as it did for many Australians during the 2017 flu season. But there may be hope.

Extending the reach of antivirals and treatment for viral pneumonia

Dr Guna Karupiah, Associate Professor of Biomedicine in the UTAS School of Medicine, is an expert in immunology and virology. He has devoted his career to researching the immune response to pox and influenza virus infections. In a major breakthrough, Dr Karupiah’s latest research has revealed that antivirals will effectively treat influenza pneumonia long after 48 hours post-onset of symptoms if they are used in combination with anti-inflammatory drugs – at least it has, to date, with mice.

‘One logical conclusion behind these findings is that our immune response is actually preventing these antivirals from working,’ Dr Karupiah said. ‘Inflammation is an important part of the body’s response against any viral infection, and pneumonia is excessive inflammation of the lung, produced when the immune system goes out of control. If it’s a new strain of virus, which our body has not been exposed to previously, the immune system overreacts to control the infection and inadvertently causes a lot of damage through inflammation. That is where the anti-inflammatories can be effective.

‘We will need to do more animal experiments to ensure that our findings are robust and reproducible. The next step would be to get funding for clinical trials in humans. That’s a while away, but it’s a big finding because we’ve been able to demonstrate it in two different viral models. If we reduce inflammation long after the onset of symptoms, we can actually make the antivirals work.’

Drawing on previous research

Dr Karupiah has extensive experience in working with mousepox, an excellent small animal surrogate model for smallpox. The mousepox model has been crucial to understanding why the smallpox virus killed up to 40 per cent of infected individuals. The mousepox virus is a mouse pathogen and has co-evolved with mice, just as the smallpox virus has co-evolved with humans. Both viruses have close similarities in terms of respiratory infection, disease and pathogenesis and are also in the same virus family.

Based on the success of the mousepox model, which provided an insight into the pathogenesis of viral infections, Dr Karupiah applied some of the findings to his research into influenza pneumonia. As had been shown by others previously, the antiviral drugs didn’t work in mice in the influenza model post-onset of symptoms, just like they don’t in humans. But when anti-inflammatory drugs were used in combination with the antivirals, the mice could be treated and fully recovered. The anti-inflammatory drugs that were used are already available for use in humans.

‘I decided to work on the antivirals because there is a huge gap in what is needed,’ Dr Karupiah said. ‘There is a lot of research in laboratories around the world in making vaccines more effective, but there’s not much going on in terms of how we can treat an individual who is already infected and presents to a doctor long after the onset of symptoms.

‘So there is a lack of treatment for people who are infected with influenza and develop pneumonia, but this problem is not unique to influenza. We’ve done this research with the mousepox model as well. We also know that, for example, the chickenpox virus can be reactivated as shingles in some adults, but the antivirals don’t work if those individuals present to a doctor 48 to 72 hours post-onset of symptoms. So my thinking is that what we’ve been able to show with the pox virus and the influenza virus models is probably going to be applicable to other viral infections as well.’

Since joining UTAS in 2016, Dr Karupiah has also been teaching in the School of Medicine. Previously he worked as a postdoctoral fellow at the National Institutes of Health (NIH, USA) at the Laboratory of Viral Diseases and then the Laboratory of Immunopathology, before returning to Australia to lead successful labs at the University of Sydney and the Australian National University.

Associate Professor Guna Karupiah (Guna) is internationally regarded as an expert on immunity to pox and other generalized viral infections. The significance and impact of his research is evidenced by the highly competitive fellowships he has held, invitations to national and international conferences and workshops, invitations to expert or advisory panels, professional activities and peer review involvement.

His current interests and research projects are immunological memory (humoral immunity), viral infection induced immunopathology (viral pneumonia, cytokine storm) and viral immune evasion.

Biography

Guna trained as a microbiologist (BSc Hons) and then specialised in medical virology and epidemiology (MSc) at the University of Malaya. After completing his PhD in viral immunology at the John Curtin School of Medical Research (JCSMR), Australian National University (ANU), he worked as a postdoctoral fellow at the National Institutes of Health (NIH, USA) at the Laboratory of Viral Diseases and then the Laboratory of Immunopathology. After returning to Australia, has headed successful labs at the University of Sydney and the ANU. He joined the School of Medicine, University of Tasmania in January 2016.

Career summary

Qualifications

PhD

Immunobiology of infection with recombinant vaccinia virus encoding murine IL-2

Australian National University

Australia

1990

MSc

Rapid diagnosis and epidemiology of dengue virus infections in Malaysia

University of Malaya

Malaysia

1986

BSc (Hons)

A biochemical and serological survey of the dengue virus epidemic in Malaysia

University of Malaya

Malaysia

1983

Senior Fellow of the Higher Education Academy, UK

 

Australian National University

Australia

2014

Languages (other than English)

Malay, Tamil, Indonesian

Memberships

Professional practice

  • American Society for Microbiology
  • American Association of Immunologists
  • American Society for Virology
  • Australasian Society for Immunology

Administrative expertise

Guna has managed a large National Institutes of Health funded research program on high-throughput screens of mice to reveal genes that confer resistance and susceptibility to class A pathogens (Poxvirus).

Teaching

Viral Immunology; Immunology; Virology; Immunopathology; Viral pneumonia; Vaccines and vaccination strategies; Immune evasion by viruses; Poxviruses; Influenza A virus; Cell-mediated immunity; Antibody responses; Cytokines; Leukocyte subsets.

Teaching expertise

  • Viral Immunology, Immunology, Virology
  • Design of 3rd year BSc Molecular Immunology course at the Australian National University

Teaching responsibility

View more on AssocProf Guna Karupiah in WARP

Expertise

  • Novel treatment of viral pneumonia
  • New strategies for viral vaccine design 
  • Understanding how the immune system works in health and disease
  • Poxvirus pathogenesis
  • Smallpox and Mousepox
  • Immune Evasion

Research Themes

Guna’s research aligns with the University’s research theme of Better Health.The long-standing focus of his research has been to understand the mechanics of an optimal immune response to viral infection with the ultimate goal of developing new efficacious vaccines and ways of intervening in the disease process if infection takes hold. As the host immune response has co-evolved with pathogens, meaningful investigations require appropriate virus-host models and this principle has guided his work. He strongly believes that understanding immune mechanisms at the molecular level through basic research using animal models is a key for translation into innovative and usable outcomes for treating infectious diseases in humans.

Collaboration

1. Modulation of the immune response by virus-encoded cytokine homologs

Dr. Geeta Chaudhri, Australian National University

Professor Mark Buller, St. Louis University, St Louis, USA

Professor Antonio Alcami, Centro de Biología Molecular Severo Ochoa, Madrid, Spain

2. Induction of long-lived antiviral humoral immunity

Dr. Geeta Chaudhri, Australian National University

Dr. Timothy Newsome, School of Molecular Bioscience, University of Sydney

Professor Robert Brink, Garvan Institute for Medical Research, Sydney

3. Systems approach to immunity and inflammation

Professor Richard Ulevitch, Scripps Research Institute, La Jolla, USA

Professor Bruce Beutler, University of Texas Southwestern, USA

Professor Alan Aderem, Seattle Biomed, Seattle, USA

Professor Garry Nolan, Stanford University, California, USA

Professor Christopher Goodnow, Garvan Institute for Medical Research, Sydney

4. Pathophysiological significance of reverse signalling through membrane TNF

Dr. Geeta Chaudhri, Australian National University

Professor Antonio Alcami, Centro de Biología Molecular Severo Ochoa, Madrid, Spain

5. Viral and host schlafen genes in inflammation and immunity to virus infection

Professor Bruce Beutler, University of Texas Southwestern, USA

Professor Antonio Alcami, Centro de Biología Molecular Severo Ochoa, Madrid, Spain

Awards

  • NHMRC Senior Research Fellowship
  • Howard Hughes Medical Institute International Research Fellowship, USA
  • University of Sydney Medical Foundation Fellowship
  • John E. Fogarty Research Fellowship, National Institutes of Health, USA

Current projects

1. Why do live viral vaccines induce life-long, protective antibody responses?

Vaccination with live viral vaccines provides life-long immunity. In contrast, inactivated vaccines induce short-lived antibody responses. In this project, the molecular and cellular basis for these differences will be investigated, utilizing novel recombinant viruses as well as transgenic, mutant and wild type mice to address some fundamental questions in immunology. It will involve techniques in immunology, virology, molecular biology and proteomics. This project is relevant for developing improved vaccination strategies.

2. A novel approach to treatment of viral pneumonia

Viral infection-induced pneumonia is a consequence of an over-exuberant immune response associated with dysregulated inflammatory cytokine production. There are no specific treatments available for viral pneumonia. We have developed a novel regime for treatment of viral pneumonia and preliminary results indicate that a combination of an antiviral plus a second compound is very effective in significantly reducing viral load, lung pathology and increasing survival even if treatment is started after onset of symptoms. This project will investigate the mechanisms through which the combination therapy ameliorates pneumonia and will assess the effectiveness of additional compounds. The project will utilize various strains of influenza A virus, wild type, gene knockout and gene knockin mice and will involving immunology, virology, molecular biology, cell signaling and histopathology techniques.

3. Mechanisms of protection of the host by virus-encoded TNF receptor homolog

Tumor necrosis factor (TNF) is a type II transmembrane cytokine (mTNF) expressed on activated cells and cleaved by a metalloproteinase to yield the soluble form (sTNF). Poxviruses encode TNF receptor (vTNFR) homologs of the extracellular domain of mammalian TNFR, which can potentially subvert the host immune response. Ectromelia virus (ECTV), an orthopoxvirus closely related to variola virus (smallpox virus) and a natural mouse pathogen, encodes a vTNFR that is secreted. This project will investigate how vTNFR modulates the host response using genetically engineered mutant viruses and gene knockout/knockin mice. It will use immunology, virology, molecular biology and cell signaling techniques. This project is highly relevant to anti-TNF therapies currently used to treat chronic inflammatory diseases.

4. Mouse and viral schlafen genes in infection and immunity

Some members of the family of human and mouse schlafen (Slfn) genes are involved in the activation and differentiation of immune cells. The mechanisms through which the Slfn proteins mediate their activities or the proteins they interact with are not known. Variola virus (VARV, the causative agent of smallpox in humans) and ectromelia virus (ECTV), a mouse-specific virus causing a smallpox-like disease (mousepox) are both poxviruses, which encode homologs of the mammalian schlafen genes. This project will investigate the mechanisms through which viral schlafen gene expression modulates the host immune response. It will utilize novel, genetically engineered mutant viruses and gene knockout/knockin mice involving immunology, virology, molecular biology and cell signaling techniques.

Fields of Research

  • Immunology (110799)
  • Medical Virology (110804)
  • Humoural Immunology and Immunochemistry (110705)
  • Cellular Immunology (110704)
  • Medical Bacteriology (110801)
  • Virology (060506)
  • Innate Immunity (110707)
  • Autoimmunity (110703)
  • Transplantation Immunology (110708)
  • Tumour Immunology (110709)

Research Objectives

  • Infectious Diseases (920109)
  • Immune System and Allergy (920108)
  • Respiratory System and Diseases (incl. Asthma) (920115)
  • Expanding Knowledge in the Medical and Health Sciences (970111)
  • Cancer and Related Disorders (920102)

Publications

Guna Karupiah has 64 publications, and has edited a book on Gamma Interferon in Antiviral Defense. His published papers appear in world class refereed journals that have an average impact factor of 7.2, placing them in the top 3.3% of international journals in the 2015 SCI Journal Citation Reports. His publications have been cited over 3,800 times as reported by the ISI Science Citation Index. In the last 5 years, his published papers have appeared in world class refereed journals that are in the top 2.5 percentile of international journals.

Total publications

14

Journal Article

(14 outputs)
YearCitationAltmetrics
2019Eldi P, Chaudhri G, Nutt SL, Newsome TP, Karupiah G, 'Viral Replicative Capacity, Antigen Availability via Hematogenous Spread, and High TFH:TFR Ratios Drive Induction of Potent Neutralizing Antibody Responses', Journal of Virology, 93, (6) ISSN 0022-538X (2019) [Refereed Article]

DOI: 10.1128/JVI.01795-18 [eCite] [Details]

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2018Duncan ML, Horsington J, Eldi P, Al Rumaih Z, Karupiah G, et al., 'Loss of actin-based motility impairs ectromelia virus release in vitro but is not critical to spread in vivo', Viruses, 10, (3) Article 11. ISSN 1999-4915 (2018) [Refereed Article]

DOI: 10.3390/v10030111 [eCite] [Details]

Citations: Scopus - 1Web of Science - 1

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2018Zanker D, Pang K, Oveissi S, Lu C, Faou P, et al., 'LMP2 immunoproteasome promotes lymphocyte survival by degrading apoptotic BH3-only proteins', Immunology and Cell Biology, 96, (9) pp. 981-993. ISSN 0818-9641 (2018) [Refereed Article]

DOI: 10.1111/imcb.12163 [eCite] [Details]

Citations: Scopus - 1Web of Science - 1

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2018Chaudhri G, Kaladimou G, Pandey P, Karupiah G, 'Propagation and Purification of Ectromelia Virus', Current Protocols in Microbiology, 51, (1) ISSN 1934-8525 (2018) [Refereed Article]

DOI: 10.1002/cpmc.65 [eCite] [Details]

Citations: Scopus - 1

Co-authors: Pandey P

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2015Chaudhri G, Tahiliani V, Eldi P, Karupiah G, 'Vaccine-Induced Protection against Orthopoxvirus Infection Is Mediated through the Combined Functions of CD4 T Cell-Dependent Antibody and CD8 T Cell Responses', Journal of Virology, 89, (3) pp. 1889-1899. ISSN 1098-5514 (2015) [Refereed Article]

DOI: 10.1128/JVI.02572-14 [eCite] [Details]

Citations: Scopus - 8Web of Science - 8

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2015Sakala IG, Chaudhri G, Scalzo AA, Eldi P, Newsome TP, et al., 'Evidence for Persistence of Ectromelia Virus in Inbred Mice, Recrudescence Following Immunosuppression and Transmission to Naive Mice', PLoS pathogens, 11, (12) pp. 1-26. ISSN 1553-7366 (2015) [Refereed Article]

DOI: 10.1371/journal.ppat.1005342 [eCite] [Details]

Citations: Scopus - 4Web of Science - 3

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2015Sakala IG, Chaudri G, Eldi P, Buller RM, Karupiah G, 'Deficiency in Th2 Cytokine Responses Exacerbate Orthopoxvirus Infection', PloS one, 10, (3) Article e0118685. ISSN 1932-6203 (2015) [Refereed Article]

DOI: 10.1371/journal.pone.0118685 [eCite] [Details]

Citations: Scopus - 5Web of Science - 5

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2014Andoniou CE, Sutton VR, Wikstrom ME, Fleming P, Thia KY, et al., 'A Natural Genetic Variant of Granzyme B Confers Lethality to a Common Viral Infection', PLoS pathogens, 10, (12) pp. 1-13. ISSN 1553-7366 (2014) [Refereed Article]

DOI: 10.1371/journal.ppat.1004526 [eCite] [Details]

Citations: Scopus - 7Web of Science - 7

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2013Gatto D, Wood K, Caminschi I, Murphy-Durland D, Schofield P, et al., 'The chemotactic receptor EBI2 regulates the homeostasis, localization and immunological function of splenic dendritic cells', Nature Immunology, 14, (5) pp. 446-453. ISSN 1529-2908 (2013) [Refereed Article]

DOI: 10.1038/ni.2555 [eCite] [Details]

Citations: Scopus - 82Web of Science - 86

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2013Horsington J, Lynn H, Turnbull L, Cheng D, Braet F, et al., 'A36-dependent Actin Filament Nucleation Promotes Release of Vaccinia Virus', PLoS pathogens, 9, (3) pp. 1-15. ISSN 1553-7366 (2013) [Refereed Article]

DOI: 10.1371/journal.ppat.1003239 [eCite] [Details]

Citations: Scopus - 27Web of Science - 20

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2013Tahiliani V, Chaudri G, Eldi P, Karupiah G, 'The orchestrated functions of innate leukocytes and T cell subsets contribute to humoral immunity, virus control, and recovery from secondary poxvirus challenge', Journal of Virology, 87, (7) pp. 3852-61. ISSN 0022-538X (2013) [Refereed Article]

DOI: 10.1128/JVI.03038-12 [eCite] [Details]

Citations: Scopus - 7Web of Science - 7

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2012Chang PP, Lee SK, Hu X, Davey G, Duan G, et al., 'Breakdown in repression of IFN-γ mRNA leads to accumulation of self-reactive effector CD8+ T cells', Journal of Immunology, 189, (2) pp. 701-10. ISSN 0022-1767 (2012) [Refereed Article]

DOI: 10.4049/jimmunol.1102432 [eCite] [Details]

Citations: Scopus - 16Web of Science - 16

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2012Lynn H, Horsington J, Ter LK, Han S, Chew YL, et al., 'Loss of Cytoskeletal Transport during Egress Critically Attenuates Ectromelia Virus Infection In Vivo', Journal of Virology (Online), 86, (13) pp. 7427-7443. ISSN 1098-5514 (2012) [Refereed Article]

DOI: 10.1128/JVI.06636-11 [eCite] [Details]

Citations: Scopus - 16Web of Science - 16

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2011Haque A, Best SE, Unosson K, Amante FH, de Labastida F, et al., 'Granzyme B expression by CD8+ T cells is required for the development of experimental cerebral malaria', Journal of Immunology, 186, (11) pp. 6148-56. ISSN 0022-1767 (2011) [Refereed Article]

DOI: 10.4049/jimmunol.1003955 [eCite] [Details]

Citations: Scopus - 104Web of Science - 102

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Grants & Funding

Guna Karupiah has held prestigious fellowships such as the Fogarty Fellowship (National Institutes of Health (NIH, USA)); the Medical Foundation Fellowship (University of Sydney); and International Research Scholar of the Howard Hughes Medical Institute (HHMI, USA), and has been successful in obtaining national and international competitive research grants. Since 1999, he has obtained individual and collaborative grants totalling over $10 million.

Funding Summary

Number of grants

1

Total funding

$23,875

Projects

Novel combination therapy for effective virus control and amelioration of influenza pneumonia (2019)$23,875
Description
There is currently no treatment available for viral pneumonia. We have developed a novel combination therapy for effective control and amelioration of influenza pneumonia. The drugs we use are currently used in humans, however not for the purpose described in the application. We do not yet know the mechanisms through which the combination treatment affords protection, and if the drugs can be administered through the respiratory route to treat influenza pneumonia effectively.We do not yet know the mechanisms through which the combination treatment affords protection, and whether the drugs can be administered through the respiratory route to treat influenza pneumonia effectively. These questions form the basis of the application. An understanding of both the mechanism(s) through which the treatment works, as well as determining an effective and practical route of delivery, will result in targeted, efficacious, and feasible clinical solutions to treatment of influenza pneumonia.
Funding
The MPST Foundation Ltd ($23,875)
Scheme
Grant
Administered By
University of Tasmania
Research Team
Karupiah G
Year
2019

Research Supervision

Guna is involved in a diverse range of teaching activities. He has extensive tertiary teaching experience in the forms of supervision of Honours, Higher Degree Research and postgraduate medical research students, undergraduate lecturing and research supervision, and international postdoctoral and postgraduate training. Since 1998, he has trained 2 Research Fellows, 5 Postdoctoral Fellows, 15 PhD students and 11 Honours students. In recognition of his contribution to teaching, training and mentoring students, he was recognised as a Senior Fellow of the Higher Education Academy, United Kingdom (2014).

He has a number of exciting Honours and PhD projects (see Current Research Projects).

Current

2

Current

DegreeTitleCommenced
PhDNovel Approaches to Treat Viral Pneumonia2017
PhDDevelopment of Enhanced Drugs Against the Causative Agents of Tuberculosis and Bacterial Pneumonia2018