Researchers in the Tiganis lab investigate the mechanisms by which obesity and metabolism influence the development of cancer.

Excess body weight is a major and leading factor in overall disease burden. In 2010 overweight and obesity were estimated to cause some 3.4 million deaths worldwide. Obesity is a key contributor to a myriad of human diseases, including cancer.

In developed countries it is estimated that approximately 20% of cancer deaths in women and 14% of cancer deaths in men are linked to obesity. Overall cancer burden is expected to double over the next 10-20 years as a direct consequence of the obesity epidemic.

Obesity increases the risk for varied human malignancies, including endometrial cancer, esophageal cancer, pancreatic cancer, post-menopausal breast cancer, colorectal cancer and liver cancer.

For example the relative risk for endometrial cancer in women with a Body Mass Index (BMI) > 40 kg/m2 is increased by greater than 6 fold. Obesity has been estimated to account for up to 40-60% of endometrial cancer incidence in developed countries.

For men the greatest risk is hepatocellular carcinoma (HCC), where risk of mortality in men with BMIs of 35-40 40 kg/m2 is increased by 4.5-fold times.

The Tiganis laboratory has had a long-standing interest in delineating the CNS and peripheral mechanisms that contribute to the development of obesity and its associated complications.

A key focus of our recently established laboratory at the Peter MacCallum Cancer Centre is to understand how obesity drives the development of cancer, including HCC, endometrial cancer and breast cancer.

More specifically, the Tiganis laboratory in interested in understanding the influence on redox balance and tumour metabolism and how obesity affects tumour immunology and immunotherapy.

People

Dr Florian Wiede, Senior Research Officer; Theme Leader
Dr Kun-Hui Lu, Research Officer
Dr Layla Zhu, Research Officer
Dr Aliki Rasmiena, Research Officer
Pei Goh, Postgraduate Student
Nicole Milanko, Honours Student

Key publications

Metabolism

Loh K, Deng H, Fukushima A, Cai X, Boivin B, Galic S, Bruce C, Shields BJ, Skiba B, Ooms L, Stepto N, Wu B, Mitchell CA, Tonks NK., Watt MJ, Febbraio MA, Crack PJ, Andrikopoulos S, and Tiganis T (2009). Reactive oxygen species enhance insulin sensitivity. Cell Metabolism.10 (4): 260-272.

Dodd GT, Decherf S, Loh K, Simonds SE, Wiede F, Balland E, Merry TL, Münzberg H, Zhang ZY, Kahn BB, Neel BG, Bence KK, Andrews ZB, Cowley MA, Tiganis T (2015). Leptin and Insulin Act on POMC Neurons to Promote the Browning of White Fat. Cell 160(1-2):88-104.

Dodd GT Andrews ZB, Simonds S, Michael NJ, DeVeer M, Brüning JC, Spanswick D, Cowley MA, and Tiganis T (2017). A hypothalamic phosphatase switch coordinates energy expenditure with feeding. Cell Metabolism. 26(2): 375-393.

Cancer

Shields B, Hauser C, Bukczynska PE, Court NW, and Tiganis T (2008). DNA replication stalling attenuates tyrosine kinase signalling to suppress S-phase progression. Cancer Cell.14(2):166–179.

Shields BJ, Wiede F, Gurzov EN, Wee K, Hauser C, Zhu HJ, Molloy TJ, O’Toole SA, Daly RJ, Sutherland RL, Mitchell CA, McLean CA, and T. Tiganis (2013). TCPTP regulates SFK and STAT3 signalling and is lost in triple negative breast cancers. Mol Cell Biol. 33, 557-570

Immunity

Wiede F, Shields BJ, Chew SH, Kyparissoudis K, van Vliet C, Galic S, Tremblay ML, Russell SM, Godfrey DI, and T Tiganis. (2011). T cell protein tyrosine phosphatase attenuates T cell signaling for the maintenance of tolerance in mice. J. Clin. Invest. 121(12):4758-74.

Wiede F, Dudakov JA, Lu KH, Dodd GT, Butt T, Godfrey DI, Strasser A, Boyd RL, Tiganis T (2017). PTPN2 regulates T cell lineage commitment and ab versus gd specification. J. Exp. Med. 214(9):2733-2758.

Research programs

Positions available

Honours and postgraduate projects 2018

Primary liver cancer is one of the world’s deadliest cancers. It is the 5th most common cancer worldwide and represents the 3rd most common cause of cancer death. Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers and is refractory to nearly all currently available anti-cancer therapies with a 5 year survival rate of <9%. In Australia HCC represents the most rapidly rising cause of cancer death. Worryingly the incidence of HCC in developed countries has been increasing driven by the obesity epidemic, the associated development of non-alcoholic fatty liver disease (NAFLD) and its progression to the more aggressive non-alcoholic steatohepatitis that results in liver fibrosis/cirrhosis. As the early stages of NAFLD/scarring are asymptomatic, patients with HCC typically present with advanced disease. Standard chemotherapy responses are poor, in most cases having no impact on overall survival rates, whereas the only targeted FDA-approved drug for HCC, Sorafenib (a multi-targeted oral tyrosine kinase inhibitor) prolongs survival by only 2-3 months. Thus there is an urgent need for new therapeutics.

Projects are available to delineate the role of reactive oxygen species (ROS) in tumour development and determine if selectively targeting redox pathways may be effective in suppressing HCC growth and maintenance.