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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 joint appointments at Monash University and the Peter MacCallum Cancer Centre, 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.

 

Education/Academic qualification

Ph.D., Biochemistry, University of Melbourne

19901994

B.Sc. (Hons), Pharmacology, University of Melbourne

19861989

Research area keywords

  • Cell Signalling
  • protein tyrosine phosphatases (PTPs)
  • obesity
  • NAFLD
  • type 2 diabetes
  • cancer
  • immunity
  • autoimmunity
  • cancer metabolism

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