Projects per year
Personal profile
Biography
Tony’s general research interest is in understanding cellular signalling networks and tissue crosstalk in human disease. He was educated at The University of Melbourne and completed his PhD with Prof. Bruce E. Kemp, St Vincent’s Institute, Melbourne, before pursuing post-doctoral training with Prof. Nicholas K. Tonks, Cold Spring Harbor Laboratory, NY. He established an independent laboratory at Monash University in 2000. He is an Editor for FEBS Journal, Molecular & Cellular Biology and Science Advances.
Tony holds an appointment at Monash University, Melbourne, Australia and heads the Monash Biomedicine Discovery Institute Metabolism, Diabetes and Obesity Program. He leads a multidisciplinary team focused on understanding the molecular mechanisms contributing to the development of obesity and diabetes and determining how obesity and metabolism affect tumour cells and the immune system to promote the development of cancer.
Biography
Current appointments/positions
2000- Laboratory Head
Department of Biochemistry and Molecular Biology
Monash University
Melbourne, Australia
2015- Head, Metabolism, Diabetes and Obesity Program
Monash Biomedicine Discovery Institute
Monash University
2016- Professor, tenured
Department of Biochemistry and Molecular Biology
Monash Biomedicine Discovery Institute
Monash University
2016- Laboratory Head
Peter MacCallum Cancer Centre
Melbourne, Australia.
2016- Director, Monash Metabolic Phenotyping Facility
Monash University Platforms
Monash University
2019- Professor Adjunct
Department of Comparative Medicine
Yale School of Medicine
Yale University
New Haven, USA.
2019- Consultant
Regeneron Pharmaceuticals
Tarrytown, NY, USA.
2020- Scientific Advisory Board Member
DepYmed Inc.
Farmingdale, NY, USA.
Previous Appointments/Positions
2016-2020 NHMRC Principal Research Fellow
Department of Biochemistry and Molecular Biology
Monash University
2016-2020 Head, Cancer Metabolism Program
Peter MacCallum Cancer Centre
2009-2014 Deputy Head of Department (Research)
Department of Biochemistry and Molecular Biology
Monash University
2010-2015 NHMRC Principal Research Fellow
Department of Biochemistry and Molecular Biology
Monash University
2010-2015 Professor, non-tenured
Department of Biochemistry and Molecular Biology
Monash University
2006-2009 NHMRC Senior Research Fellow (Level A)
Department of Biochemistry and Molecular Biology
Monash University
2006-2009 Associate Professor, non-tenured
Department of Biochemistry and Molecular Biology
Monash University
2003-2005 Senior Lecturer, Non-tenured
Department of Biochemistry and Molecular Biology
Monash University
2001-2002 Lecturer (non-tenured)
Department of Biochemistry and Molecular Biology
Monash University
2000-2005 Monash University Logan Fellowship, Non-tenured
Department of Biochemistry and Molecular Biology
Monash University
2000-2003 NHMRC R. Douglas Wright Fellow
Department of Biochemistry and Molecular Biology
Monash University
1999 Senior Research Officer
St. Vincent’s Institute of Medical Research
Fitzroy, Victoria 3065, Australia.
1997-1998 Post-Doctoral Research Fellow (C.J. Martin Fellow)
St. Vincent’s Institute of Medical Research
1995-1997 Post-Doctoral Research Fellow (C.J. Martin Fellow)
Cold Spring Harbor Laboratory
Cold Spring Harbor, NY 11724, USA.
1994-1995 Research Officer
St. Vincent’s Institute of Medical Research
Awards and Honours
1990 Melbourne University Postgraduate Scholarship
1995 C.J. Martin Fellowship, NHMRC
1998 AMRAD Post-Doctoral Award
1999 St. Vincent’s Hospital Research Week, Senior Investigator Prize
1999 Finalist, Metcalf Research Fellowship
Walter and Eliza Hall Institute of Medical Research
2000-2005 Logan Research Fellowship, Monash University.
2000-2003 R. Douglas Wright Award, NHMRC
2006-2010 Senior Research Fellowship, Level A, NHMRC
2009 Deans Award in Excellence in Research
(Distinguished Research Career)
Faculty of Medicine, Nursing and Health Sciences
Monash University
2011-2015 Principal Research Fellowship, NHMRC
2016-2020 Principal Research Fellowship, NHMRC
Research interests
For more than 20 years Prof Tiganis has focussed on understanding the role of tyrosine-phosphorylation-dependent cell signalling in biology and disease. Aberrations in tyrosine-phosphorylation-dependent cell signalling contribute to a wide variety of human diseases. Not surprisingly, drugs targeting protein-tyrosine-kinases (PTKs) have been clinically approved for many disorders. By contrast, protein-tyrosine-phosphatases (PTPs), which function together with PTKs to coordinate tyrosine-phosphorylation-dependent cell signalling, have been comparatively underexplored and erroneously considered undruggable. Prof Tiganis’ long-standing contributions to the field have been instrumental in dispelling common misconceptions that have hampered progress and prevented the exploitation of PTPs as drug candidates alongside their PTK counterparts. His work on PTPs has led to paradigm shifting discoveries and defined new treatment opportunities for diseases such as obesity and cancer now poised for clinical translation.
His PTP centric, but multidisciplinary and integrative research program has led to seminal discoveries across the fields of metabolism, immunology and cancer.
Notable examples include:
1. Defining the importance of redox balance in metabolism and cancer:For more than 10 years his lab has explored the regulation of PTPs by reactive oxygen species (ROS). In 2009 he published a seminal article in Cell Metabolism that established that ROS could promote insulin sensitivity in vivo by inhibiting PTPs in muscle to alleviate the development of insulin resistance, a key pathological feature of type 2 diabetes. This paradigm shifting work challenged the prevailing dogma that ROS were exclusively detrimental in type 2 diabetes. This and subsequent studies from his lab have helped focus the ROS field on the importance of redox balance and underscored the dangers of antioxidants in metabolic health.
Conversely, his lab has also shown how redox imbalance and oxidative stress can result in the oxidation and inactivation of PTPs to perturb hepatic insulin signalling and promote obesity as well as the progressive development of liver disease and liver cancer. The latter seminal study published in Cell in 2018 explained the growing incidence of liver cancer in obese people in the absence of advanced liver disease/fibrosis. This finding overturned the prevailing dogma that liver cancer must be preceded by advanced liver disease. This discovery highlighted the need for independent screening for liver cancer in obese patients. The significance and impact of this work was underscored by the commentaries in leading journals such as Cancer Discov, Cell Metab, Nat Rev Endocrinol, Nat Rev Cancer, Nat Rev Gastroenterol Hepatol and Hepatobiliary Surg Nutr (x4).
His laboratory continues to explore the importance of redox balance and PTPs in obesity, NAFLD, metabolic health and aging.
2. Defining mechanisms governing T cell tolerance and exploiting these for cancer immunotherapy:In the last 10 years hehas explored the regulation of T cell signalling by PTPs and revealed a fundamental mechanism by which T cells differentiate self from foreign pathogens to prevent autoimmunity. This work not only revealed how loss-of-function PTPN2 polymorphisms can contribute to the development of autoimmunity in humans, but also provided the foundation for establishing PTPN2’s critical role in cancer immune surveillance. He has shown that PTPN2 functions as an intracellular checkpoint in T cells, with functions reminiscent of the immune checkpoint PD-1, the blockade of which has revolutionized cancer therapy. He has shown that the inhibition of PTPN2 can similarly enhance the ability of T cells to eradicate cancer. Importantly, he has shown that targeting PTPN2 in CAR T cells, which are highly effective in blood cancers, can extend their utility to combating solid tumours. This work has formed the basis of patents (3 PCT) that have garnered significant attention form the pharmaceutical industry and with Cell Therapies at PMCC an imminent proof-of-concept clinical trial to explore the efficacy of genetically-engineered PTPN2-null CAR T cells in human cancer.
3. Defining mechanisms by which the brain coordinates energy balance and exploiting these to combat obesity:In the last 5 years his work on PTPs in the brain has provided insight into fundamental mechanisms by which the brain controls body weight and glucose metabolism. In particular, his work published in Cell in 2015 defined the critical role of brain in responding to peripheral factors such as insulin and leptin to increase energy expenditure by promoting the conversion of white adipocytes that store fuels into brown-like adipocytes that expend energy. He has shown the brain’s capacity to respond to peripheral signals in obesity is abrogated by the activities of PTPs and that this contributes to weight gain and diabetes. He has shown these PTPs can be effectively drugged via the intranasal route to promote weight loss in obesity. These findings are protected by a patent (PCT) and have formed the basis of a translational program with chemists and clinicians at Monash University aimed at combating obesity and diabetes in humans with an intranasal spray.
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
Education/Academic qualification
Ph.D., Biochemistry, University of Melbourne
1990 → 1994
B.Sc. (Hons), Pharmacology, University of Melbourne
1986 → 1989
Research area keywords
- Cell Signalling
- protein tyrosine phosphatases (PTPs)
- obesity
- NAFLD
- type 2 diabetes
- cancer
- immunity
- autoimmunity
- cancer metabolism
Network
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The impact of obesity on anti-tumour immunity in triple negative breast cancer
Tiganis, T., Goh, P., Rematta, M., Warnecke, E., McLean, C., Darcy, P. & Baell, J.
1/01/22 → 31/12/25
Project: Research
-
Targeting Immune Checkpoints In Obesity-Driven HCC
Wiede, F., Tiganis, T., Darcy, P., Johnstone, R. W., McLean, C. & Febbraio, M.
1/07/21 → 30/06/23
Project: Research
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Full Application for DoD Breakthrough Award Level 2: Targeting PTPN2 to promote anti-tumor immunity in triple negative breast cancer
Tiganis, T., McLean, C., Loi, S. & Wiede, F.
1/03/21 → 29/02/24
Project: Research
-
Next Generation Cell Therapies for Cancer
Tiganis, T., Huntington, N., Darcy, P., Zhang, Z., Cursons, J. & Vivier, E.
1/12/19 → 31/12/23
Project: Research
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Erratum: Elevated Hypothalamic TCPTP in Obesity Contributes to Cellular Leptin Resistance (Elevated Hypothalamic TCPTP in Obesity Contributes to Cellular Leptin Resistance (2011) 14(5) (684–699), (S1550413111003573), (10.1016/j.cmet.2011.09.011))
Loh, K., Fukushima, A., Zhang, X., Galic, S., Briggs, D., Enriori, P. J., Simonds, S., Wiede, F., Reichenbach, A., Hauser, C., Sims, N. A., Bence, K. K., Zhang, S., Zhang, Z. Y., Kahn, B. B., Neel, B. G., Andrews, Z. B., Cowley, M. A. & Tiganis, T., 1 Nov 2022, In: Cell Metabolism. 34, 11, p. 1892 1 p.Research output: Contribution to journal › Comment / Debate › Other › peer-review
Open Access -
PTP1B Is an Intracellular Checkpoint that Limits T-cell and CAR T-cell Antitumor Immunity
Wiede, F., Lu, K-H., Du, X., Zeissig, M. N., Xu, R., Goh, P. K., Xirouchaki, C. E., Hogarth, S. J., Greatorex, S., Sek, K., Daly, R. J., Beavis, P. A., Darcy, P. K., Tonks, N. K. & Tiganis, T., 1 Mar 2022, In: Cancer Discovery. 12, 3, p. 752-773 22 p.Research output: Contribution to journal › Article › Research › peer-review
Open Access23 Citations (Scopus) -
Insulin signaling in AgRP neurons regulates meal size to limit glucose excursions and insulin resistance
Dodd, G. T., Kim, S. J., Méquinion, M., Xirouchaki, C. E., Brüning, J. C., Andrews, Z. B. & Tiganis, T., 24 Feb 2021, In: Science Advances. 7, 9, 18 p., eabf4100.Research output: Contribution to journal › Article › Research › peer-review
Open Access11 Citations (Scopus) -
Ptpn2 and KLRG1 regulate the generation and function of tissue-resident memory CD8+ T cells in skin
Hochheiser, K., Wiede, F., Wagner, T., Freestone, D., Enders, M. H., Olshansky, M., Russ, B., Nüssing, S., Bawden, E., Braun, A., Bachem, A., Gressier, E., McConville, R., Park, S. L., Jones, C. M., Davey, G. M., Gyorki, D. E., Tscharke, D., Parish, I. A., Turner, S., & 4 others , 29 Apr 2021, In: Journal of Experimental Medicine. 218, 6, 21 p., e20200940.Research output: Contribution to journal › Article › Research › peer-review
5 Citations (Scopus) -
Skeletal muscle NOX4 is required for adaptive responses that prevent insulin resistance
Xirouchaki, C. E., Jia, Y., McGrath, M. J., Greatorex, S., Tran, M., Merry, T. L., Hong, D., Eramo, M. J., Broome, S. C., Woodhead, J. S. T., D'Souza, R. F., Gallagher, J., Salimova, E., Huang, C., Schittenhelm, R. B., Sadoshima, J., Watt, M. J., Mitchell, C. A. & Tiganis, T., 17 Dec 2021, In: Science Advances. 7, 51, 24 p., eabl4988.Research output: Contribution to journal › Article › Research › peer-review
Open Access13 Citations (Scopus)