Tiganis Lab research
About Professor Tony Tiganis
Professor Tony Tiganis is internationally-recognised as an expert on cellular signalling. His work has led to fundamental discoveries across the fields of metabolism, immunology and cancer with regular last author publications in top-ranking journals that have been highly influential.
He is one of Australia’s leading scientists in obesity and type 2 diabetes research and leads Monash University’s Biomedicine Discovery Institute Metabolism Diabetes & Obesity Program, arguably one of Australia’s leading programs in metabolism research.
More recently, Prof Tiganis has shifted his attention to understanding how obesity and type 2 diabetes contribute to the development of other diseases, especially cancer. In developed countries, obesity and type 2 diabetes are considered to be leading drivers of some 13 different types of cancer, including liver cancer and breast cancer which are the focus of research in the Tiganis lab.
The Tiganis lab investigates the signalling pathways underpinning the development of obesity, type 2 diabetes and co-morbidities, including non-alcoholic fatty liver disease and cancer.
The Greek physician Hippocrates (460-377 BCE) the father of modern medicine recognised the influence of obesity on health stating that ‘sudden death is more common in those who are naturally fat than in the lean’ and that ‘corpulence is not only a disease itself, but the harbinger of others’. Obesity has now reached epidemic proportions and is the single most important driver of morbidity and mortality in the modern world.
At present >25% of the world’s population is overweight. Excess body weight is a leading factor in overall disease burden worldwide and if left unabated will lead to falls in overall life expectancy.
Obesity is a key contributor to a myriad of human diseases including type 2 diabetes, cardiovascular disease, autoimmune diseases, liver disease, chronic kidney diseases and some 13 different cancers.
Educational and lifestyle intervention approaches have done little to curb the escalating trend toward the overweight and obese state. At present, 650 million people worldwide are obese and this is predicted to rise to 1 billion by the year 2030. Thus, it is imperative that we develop new therapies to assist with weight loss, as well as specific therapies for the diseases that obesity triggers.
Our goal is to dissect the molecular mechanisms and develop new therapies for obesity and its comorbidities.
To this end we take a multidisciplinary and integrative approach that spans the fields of neuroendocrinology, metabolism, immunology and cancer to understand the complex pathophysiological process contributing to the development of obesity, type 2 diabetes and complications such as liver disease and cancer.
Our research is undertaken at Monash University’s Biomedicine Discovery Institute, and since 2016 also at the Peter MacCallum Cancer Centre. Our strategic presence across these world-renowned institutions affords us access to expertise in metabolism, cancer and immunotherapy and clinicians who can facilitate the translation of our findings to the clinic.
- Defining CNS and peripheral mechanisms governing energy balance and glucose homeostasis
- Understanding how exercise promotes metabolic health
- Understanding how obesity and type 2 diabetes affect the development of cancer
- Developing next generation CAR T and CAR NK cells to combat cancer
Visit Professor Tiganis' Monash research profile to see a full listing of current projects.
Our researchers are committed to understanding the causes of metabolic disease and obesity,
and the links between obesity and other health issues.
Understanding the role of ROS in metabolism & ageing
Supervisors: Prof. Tony Tiganis and Dr. Chrisa Xirouchaki
According to the World Health Organisation, the proportion of people worldwide greater than 60 years old will double in the next three decades. By 2031 more than 6 million Australians (~19%) will be over 65 years old and this will increase to 9-11 million by 2061 (~25%). The incidence of type 2 diabetes increases markedly with age. It is therefore anticipated that our ageing population will be accompanied by a dramatic increase in the incidence of type 2 diabetes. One of the main reasons for the increasing onset of type 2 diabetes with age is the development of insulin resistance. The age-associated decline in insulin sensitivity has been attributed to reductions in physical activity and associated weight gain and decreases in muscle mass (sarcopenia). However, the precise cellular and molecular mechanisms by which physical inactivity facilitates the development of insulin resistance remain unknown. Our exciting unpublished studies demonstrate that decreased exercise-induced reactive oxygen species (ROS) production in skeletal muscle with ageing may be a key driver of insulin resistance.
Projects are available to explore how perturbations in redox balance contribute to the age-associated decline in insulin sensitivity and the development of type 2 diabetes.
Targeting the brain to combat obesity & diabetes
Supervisors: Prof. Tony Tiganis and Prof. Zane B. Andrews
Large genome-wide association studies and meta-analyses indicate that >20% of BMI variation may be accounted for by common genetic variation and have highlighted the principal importance of CNS pathways in obesity. The hypothalamus is critical in the control of energy balance and glucose homeostasis. Within the hypothalamus, the arcuate nucleus is proximal to a ‘leaky’ blood brain barrier that allows for the entry of circulating factors, such as leptin and insulin. Leptin and insulin act on hypothalamic neurons to coordinate appetite/feeding, energy expenditure and glucose homeostasis.
Our work has identified fundamental mechanisms by which the brain controls body weight and glucose metabolism. In particular, our work published in Cell in 2015 defined the critical role of brain in responding to insulin and leptin to increase energy expenditure by promoting the conversion of white adipocytes that store fuels into brown-like adipocytes that expend energy. We have shown the brain’s capacity to respond to peripheral signals in obesity is abrogated by the activities of protein tyrosine phosphatases (PTPs) and that this contributes to weight gain and diabetes. We have shown these PTPs can be effectively drugged via the intranasal route to promote weight loss in obesity. These findings have formed the basis of a translational program with chemists and clinicians at Monash University aimed at combating obesity in humans with an intranasal spray.
Projects are available to dissect the role of hypothalamic PTPs in energy balance and glucose homeostasis and to exploit the intranasal route to target hypothalamic PTPs in obesity and the metabolic syndrome.
Understanding how chronic stress promotes obesity & diabetes
Supervisor: Prof. Tony Tiganis
Contrary to popular belief overweight/obesity and diabetes are not just problems of developed nations, but are now also on the rise in low- and middle-income countries. Indeed, the greatest increases in diabetes have occurred in developing nations, especially in the Asian-Pacific region. The question is why is this occurring? Although the reasons are undoubtedly multifactorial and include complex genetic, socioeconomic, lifestyle and environmental factors (e.g. food availability), there is growing evidence that additional factors associated with ‘westernisation’ or modernisation must be contributing to the ever-growing societal BMIs and declining metabolic health.
Chronic stress is a seemingly unavoidable consequence of modernisation. Clinical and epidemiological studies have demonstrated unequivocally that chronic stresses increase morbidity and shorten lifespan in humans. Increasing work-related demands, psychosocial stress, low socioeconomic status and low social rank are widely considered to be major contributors to mortality and the development of chronic diseases.
Projects are available to determine if chronic stress may influence homeostatic mechanisms in the brain that govern energy balance and glucose homeostasis to contribute to obesity and diabetes.
CNS and peripheral mechanism governing energy balance and glucose homeostasis.
Our research investigates mechanisms and how these are influenced -by stress and with age - to contribute to
the development of obesity and type 2 diabetes.
Understanding how obesity drives the development of liver disease & HCC
Supervisors: Prof. Tony Tiganis, Dr. Florian Wiede and Dr. Spencer Greatorex
Obesity is a leading factor in the development of liver disease, with >85% of overweight individuals developing non-alcoholic fatty liver disease (NAFLD). NAFLD encompasses a broad spectrum of liver conditions ranging from simple steatosis, to the more severe and progressive non-alcoholic steatohepatitis (NASH), a condition that results in fibrosis and if left unresolved, cirrhosis (late stage liver disease) and/or liver cancer. Obesity-associated NASH is currently the third leading cause for liver transplantation and is expected to soon surpass hepatitis C as the principal cause for liver transplantation and hepatocellular carcinoma (HCC) in the developed world. At present the molecular mechanisms underpinning the NAFLD continuum and the development of HCC remain unclear. Moreover, there are no effective therapies for NASH with fibrosis/cirrhosis or HCC.
Projects are available to determine the mechanisms by which obesity drives the development of NASH, fibrosis and HCC.
Obesity, NAFLD and liver cancer. Our laboratory is interested in how obesity promotes the development of non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH)/fibrosis and hepatocellular carcinoma (HCC). A key focus is the role reactive oxygen species (ROS) and the importance of redox balance.
Targeting immune checkpoints in HCC
Supervisors: Prof. Tony Tiganis, Dr. Florian Wiede and Dr. Mara Zeissig
HCC is the most rapidly rising cause of cancer death in Australia. The obesity epidemic and the accompanying development of NALFD have become major drivers of HCC in the developed world. If left unresolved, NAFLD can progress and result in severe fibrosis or cirrhosis and/or HCC. There are no effective therapies for advanced HCC. Although surgical resection and liver transplantation are effective for early stage HCC, the majority of patients present with advanced disease, when neither surgery, chemotherapy, ionizing radiation nor targeted therapies (Sorafenib) are effective. Thus, there is an urgent need for the development of effective therapeutics. Pre-clinical studies point towards the suppression of the immune system being fundamental for HCC development. However, recent phase III trials for HCC have been disappointing, with the Merck’s PD-1 blocking antibody Keytruda (pembrolizumab) failing to achieve any significant improvements in survival.
Our pilot studies suggest that the lack of efficacy of anti-PD-1 monotherapy in HCC might be due to HCC engaging multiple redundant immune checkpoints. We posit that the combinatorial targeting of several immune checkpoints will be necessary to combat HCC in obesity.
Projects are available to assess the therapeutic potential of targeting multiple immune checkpoints in HCC.
Understanding how obesity influences the development & treatment of breast cancer
Supervisors: Prof. Tony Tiganis, Dr. Florian Wiede and Dr. Mara Zeissig
The influence of obesity on cancer and immunotherapy. Our laboratory is interested in elucidating how obesity influences the development and treatment of cancer and the extent to which this involves changes in the immune system
There is now compelling evidence for obesity being a key factor in the progression of human malignancies, including breast cancer. Indeed, according to the US Centre for Disease Control, some 40% of all cancers diagnosed in the last decade can be linked to obesity. The increasing prevalence of adult obesity and the alarming increase in childhood obesity, coupled with our ageing population, is creating a perfect storm for obesity-driven cancer that is predicted to double the incidence of cancer in the next 10-20 years.
In addition, to contributing to the genesis and progression of cancer, obesity can also markedly influence therapy. Thus, it is critical that we define the mechanisms by which obesity influences cancer development, progression and therapy to effectively respond to this impending crisis.
Obesity is a marker of poor prognosis in breast cancer in both pre- and post-menopausal women. In particular, more women with triple negative breast cancer (TNBC) are overweight (BMI>25) or obese (BMI>30) than normoweight and obese patients with TNBC have a poor prognosis.
Projects are available to determine the mechanisms by which obesity contributes to the development of TNBC and influences the response to therapy, especially immunotherapy.
We collaborate with many scientists and research organisations around the world. Click on the map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).
Student research projects
The Tiganis Lab offers a variety of Honours, Masters and PhD projects for students interested in joining our group. There are also a number of short term research opportunities available.
Please visit Supervisor Connect to explore the projects currently available in our Lab.