Liver Cancer Unit

Help fight the fastest increasing cause of cancer mortality in Australia

A problem doesn’t go away if you ignore it, and liver cancer has been ignored by the general public for far too long.

We’ve reached the point where liver cancer is the fastest increasing cause of cancer mortality in Australia. It also sits as the third most common cause of cancer death, worldwide.
1,643 people a day are dying of liver cancer.

The stats paint a very scary picture, but here at GMRF we see beyond the numbers and figures. The real impact of liver cancer is not in its numbers but in the countless lives it is devastating each day.

As we are based at Greenslopes Private Hospital and conduct a range of clinical trials in cancer treatment, we see firsthand this disease taking the lives of people who should have many years still ahead of them.

With your help, we are doing something about, and we have a very clear vision for our research…

We are committed to innovative research that can change cancer from a death sentence to a treatable chronic illness within our lifetime.

It’s an ambitious but achievable goal – with support. You can help fight this rapidly increasing cancer.

GMRF has the only dedicated liver cancer research facility in Queensland.

That is what your donation to GMRF can achieve – creating solutions to one of the biggest health issues our country, and indeed our world, is facing.

Head of the Liver Cancer Unit, Dr Jason Steel, describes the focus…

“At present there is only a single drug that can improve survival times of patients with liver cancer. It prolongs live by months and rarely cures the cancer. Many people do not respond to this treatment yet it is our best drug currently available.  We need new treatments that can give hope to patients who have advanced liver disease. Our work looks at new ways to target and kill cancer with the hope that new treatments will come out of this work.”

In short…

We’re not the ‘all of the eggs in one basket’ types, which is why we have developed a multi-pronged approach when it comes to tackling liver cancer. Our current research focus is in three key areas

Development of a cancer killing virus:  We are starting to test whether our new viruses can be used as a treatment for liver cancer. We will test whether they can specifically target and kill the cancer while leaving normal cells untouched.

Immunotherapy for liver cancer: we are examining new drug combinations to block and kill the cells that inhibit our immune system killing the cancer. We will start to look at combining these blocking agents with cancer vaccines.

Anti-metastatic therapies: We are evaluating new drugs we have identified that have the potential to block the spread of cancer. We will also attempt to find a number of new drugs that might also show these characteristics.

 

 

 

 

600,000
people die from
liver cancer
every year

our projects

In detail…

Immunology of liver cancer

In the process of cellular transformation, from normal cells to cancer, the cell undergoes a number of mutations, which often leads to the expression of tumour-associated antigens (TAAs) on the surface of these cancer cells. The immune system can recognise these TAA and generate an immune response targeted against the tumour.

These TAA are not expressed or have reduced expression on normal cells making them good targets for the immune system.  However, cancer cells have developed ways to subvert the immune system so that it is ineffective against the cancer. One of the focus areas of our research is to examine how liver cancer is able to achieve this.  To do this we use mouse models, cell culture and human patient samples. Once we identify ways in which the cancer can subvert the immune system, we can identify ways to inhibit them leading to stronger immune responses against the liver cancer.

Immunotherapeutic approaches to liver cancer

Here we use our knowledge of the immunology of liver cancer to develop ways to teach our immune system to target and kill the cancer.  Our research focuses on developing liver cancer vaccines and other immune-stimulatory therapies to achieve this.  Using genetically modified viruses as vaccines we direct the immune system to kill the liver cancer without harming normal cells, thereby reducing the side-effects commonly seen with other cancer treatments, such as chemotherapy and radiation. We use mouse models of liver cancer to pre-clinically test our immunotherapy strategies.

Liver cancer stem cells

Increasing evidence supports the concept that a specialized population of cancer cells within a tumour possess characteristics of self-renewal and have the ability to give rise to all cell types in a particular cancer.

These 'cancer stem cells' also exhibit characteristics that render them resistant to both radiation and chemotherapy. There is also increasing evidence that the cancer stem cell may be responsible for tumour recurrence following tumour remission. One of the major focuses of our research is to investigate liver cancer stem cells to understand the origins of liver cancer and to develop treatments to target the liver cancer stem cell.

The team

Dr Jason Steel

Dr Jason C Steel, Ph D

Dr Steel obtained his PhD in Cancer Gene Therapy from Charles Sturt University in 2004.  The following year, Dr Steel  was awarded a National Institutes of Health - Fogerty International Research Fellowship to train at the National Cancer Institute in America. While there, Dr Steel worked within cancer gene therapy and the Cytokine Immunology and Immunotherapy Laboratories of  Professor John Morris and Dr Thomas A Waldmann. During Dr Steel’s 6 years at the NIH he gained extensive experience in cancer immunology and immunotherapy and saw some of his work translated into human clinical trials for cancer.  He was awarded the prestigious NIH Fellows Award for Research Excellence on three separate occasions as well as the Society for Immunotherapy of Cancer Presidential Travel Award.  

In 2010, Dr Steel moved to the University of Cincinnati College of Medicine in the US as an Assistant Professor in the Hematology and Oncology Department.  At the University of Cincinnati Dr Steel‘s lab worked on the development and pre-clinical testing of cancer vaccines, cancer immunology and the identification and characterisation of cancer stem cells.    

In 2014, Dr Steel returned to Australia to take up a research position at UQ and the Gallipoli Medical Research Foundation where he is working on how liver cancer escapes detection of the immune system and how we can counter this by teaching our immune system to attack the liver cancer.



Dr Aparna Jayachandran

Dr Aparna Jayachandran is a laboratory-based early career cancer researcher within the Gallipoli Medical Research Institute and the Faculty of Medicine at the University of Queensland. She is currently appointed as a Research Officer within the Liver Cancer Unit. Dr Jayachandran’s research work has focused on her expertise in the research areas of Hepatocellular Carcinoma (HCC) biology, epithelial -mesenchymal transition (EMT), cancer stem cells (CSC) and metabolic reprogramming. During her PhD (University of Giessen, Germany & Mount Sinai School of Medicine, New York, USA), she identified the relevance of EMT in organ fibrosis.

During her postdoctoral training at LICR, Melbourne, Australia, she investigated how metabolic reprogramming and EMT of melanoma cells can boost their motility. After joining the Liver Cancer Unit in October 2015, she is extending her knowledge into HCC biology. She is currently investigating the mechanistic associations between EMT, metabolic reprogramming, immune evasion and CSCs, so as to identify and develop druggable targets in HCC.

 

Liver Research Unit

Your hardworking liver

Let’s be honest, most of us don’t give much thought to our liver. This workhorse of an organ is quietly plugging away in the background, performing around 500 functions in our body such as removing toxins and producing bile which aids in digestion fat.

Your liver can do a lot, but it struggles to handle the excessive levels of salt and sugar many of us consume in our modern, processed diet.

It is when the build-up of toxins gets too much for this overworked organ that you become at risk of developing fatty liver disease.

The liver health crisis flying under the radar

With one in three adult Australians developing fatty liver disease, it’s fair to say it is reaching epidemic proportions in this country. The big problem is many people aren’t even aware they have it. Fatty liver disease often presents no symptoms, particularly in the early stages, and can progress to even more significant health concerns.

Fatty liver disease is associated with an increased risk of heart disease and diabetes. Worse still, if fatty liver disease reaches cirrhosis, which is hardening and scarring of the liver, progression to liver cancer becomes a real possibility. Click here to read more about our liver cancer research.

So what are we doing about the epidemic of fatty liver disease?

As it stands, the best known treatment for fatty liver disease is dramatic life-style changes. The Gallipoli Medical Research Foundation (GMRF) Liver Research Unit is working to better understand fatty liver disease so we can better treat it.

The Liver Research Unit receives 100% of its funding from GMRF donors, and this team is committed to producing results that can provide solutions for people who are suffering from an illness of the liver.

the most common
risk factor for
liver cancer is
chronic viral
hepatitis

Our research focus

Your hardworking liver

Co-Toxic Liver Disease:

A major focus of the Liver Research Centre’s work is the pathophysiological basis of the co-toxic effects of iron, alcohol and steatosis on the liver, and to establish the role that iron plays in accelerating the progression of liver diseases due to alcohol and/or non-alcoholic fatty liver disease. We have a number of animal models to study the interrelationships between alcohol, high fat diets and iron. The role that iron plays in the progression of advanced liver disease of all aetiologies is also a core area of a study in the centre. We are studying the effects of increased liver iron stores on waiting list mortality and on the natural history of advanced liver disease, hoping ultimately to improve the duration and quality of life of affected patients.

Liver Fibrogenesis:

The ultimate end point of nearly all liver insults is hepatic fibrosis and cirrhosis (i.e. liver scarring). Despite recent advances in antiviral therapy, the majority of liver diseases are relentlessly progressive. Therefore, targeting the fibrogenic process to delay disease progression would likely reduce morbidity and mortality from liver disease. Our researchers are investigating potential antifibrotic agents in vitro and in vivo and studying the cellular and molecular mechanisms that underlie the pathogenesis and reversal of hepatic fibrosis.
The ultimate aim of this research is to identify an effective antifibrotic and to conduct a large clinical trial involving human subjects with liver disease.

Non-HFE Haemochromatosis:

It is apparent that approximately 5% of patients with hepatic iron overload do not carry either of the conventional HFE mutations. We have studied a number of families and have demonstrated mutations in various genes involved in iron metabolism in most patients. However, there remain a significant number of patients in whom the iron loading disorder is unexplained. We will extend our clinical observations in this field incorporating the use and development of new diagnostic strategies, as well studies of iron biology in animal models of non-HFE haemochromatosis. We aim to become the primary reference centre for non-HFE haemochromatosis in the Asia-Pacific Region.

Australia, it’s time to love your liver!

The good news is that fatty liver disease is reversible. There are a number of ways you can be reducing your risk of developing fatty liver disease, or reducing its impact if you’ve been diagnosed.

Here are five ways you can love your liver. They might seem hard to accomplish, but the benefit to your liver and overall health will most likely be worth it!

The other thing you can do is start spreading the word about the state of Australia’s liver health. Fatty liver disease has flown under the radar for far too long. We want you to join us in talking to as many people you can so that together we can start reversing the alarming increase of fatty liver disease, and prevent even more people facing a battle with liver cancer.

The team

Professor Darrell Crawford

Darrell Crawford is the Head of the School of Medicine at The University of Queensland and a Professor of Hepatology at that institution. He is a highly respected clinician and clinical scientist with 25 years of service to the discipline of Hepatology with special expertise in disorders of iron overload, liver transplantation medicine and viral hepatitis. Professor Crawford is the past president of the Gastroenterological Society of Australia (2008/2009) which is the peak clinical, research and professional body representing gastroenterologists and hepatologists in Australia. He is a past chairman of the Australian Liver Association (2001-2005), the current President of Council of The Asian Pacific Association for the Study of the Liver and an invited member of its Scientific Program Committee (2014), member of the international advisory board for Abbott Pharmaceuticals as well as national advisory boards for Roche, Schering Plough, Gilead, Jensen Cilag and Novartis. He is a frequent invited speaker at national and international gastroenterology and hepatology meetings.

Professor Nathan Subramaniam

Prof Nathan Subramaniam is Head of the Membrane Transport Laboratory at the Queensland Institute of Medical Research, Professor at the School of Medicine, Director of Non-HFE Research, and Director The Liver Research Centre, University of Queensland. He is an internationally recognised researcher in cell biology, non-HFE iron overload and iron biology, and has made significant impacts in these fields. High impact publications in Science and Nature were the first to describe novel vesicular trafficking receptors. Major publications in Lancet, Blood, Gastroenterology and Hepatology were instrumental in defining the role of the liver as the central regulator of iron homeostasis and the function of transferrin receptor 2 and HFE. He has been invited to present his work at major national and international meetings. He is on the Council of the Gastroenterological Society of Australia, Executive Committee of the Australian Liver Association, and the Queensland ASMR committee. He is an Associate Editor of the World Journal of Gastroenterology and member of 3 other Editorial Boards.

Dr Kim Bridle

Dr Bridle has made a number of important contributions to both haemochromatosis and fibrosis research through publications in high quality journals including The Lancet, Hepatology and The American Journal of Pathology. Dr Bridle’s achievements have been recognised by a number of highly competitive awards including: ASMR Young Investigator Award, Gastroenterological Society of Australia (GESA) Travel Award, American Liver Foundation Post-Doctoral Award, AstraZeneca/GESA Career Development Award, University of Queensland Early Career Researcher Award, Pfizer/GESA Postdoctoral Research Fellowship and a Princess Alexandra Hospital Research Award. Dr Bridle has been an invited speaker at the annual meeting of the Gastroenterology Society of Australia, the Australian and New Zealand Liver Transplant meeting and the Australian Liver Association meeting.

Dr Katherine Stuart

Dr Stuart graduated from the University of Queensland in 1987. She trained in Gastroenterology and Hepatology at the Mater Adult and Royal Brisbane Hospitals, before spending a year in London with Professor Roger Williams. Upon returning to Brisbane she was the Hepatology Liver Transplant Fellow at the Princess Alexandra Hospital before embarking on a PhD investigating the mechanisms and significance of iron accumulation in cirrhosis. Katherine was the Director of Physician Training at the Princess Alexandra Hospital between 2003 and 2007. She has been the Director of Hepatology at Princess Alexandra Hospital since 2009 and is a senior member of The Queensland Liver Transplant Service. Her research interests include hepatocellular carcinoma and viral hepatitis. Katherine is in private practise at Greenslopes Private Hospital and is an active member of the Clinical Trials Unit at the Gallipoli Medical Research Foundation.

 

Professor Jonathan Fawcett

Professor Fawcett is currently Director of The Queensland Liver Transplant Service and Professor of Hepatopancreaticobiliary Surgery and Consultant Surgeon, University of Queensland. Professor Fawcett’s current clinical interests include all aspects of liver and pancreatic surgery, including laparoscopic resection and liver transplantation with particular experience in transplantation in childhood. His research interests include hepatocellular carcinoma and liver transplantation. Professor Fawcett is a member of numerous professional societies including the General Surgeons Australia; Australian HepatoPancreaticoBiliary Association; Transplantation Society of Australia and New Zealand (currently Treasurer); International HepatoPancreaticoBiliary association; International Liver Transplantation Society and The Transplantation Society. Professor Fawcett is currently Principle Supervisor of one PhD student and is involved with examination and instructing for the Royal Australasian College of Surgeons, evidence of his commitment to training and education of young clinicians.

Dr Mandy Heritage

Mandy undertook her PhD at the Queensland Institute of Medical Research. After 4 years of postdoctoral studies at Oxford University she returned to the LRC in 2007 to undertake research into iron metabolism in co-toxic liver disease.

Ms Lesley Jaskowski

Lesley joined the LRC in 2009. She has over 20 years experience working in hepatitis research. Lesley is now involved in projects examining iron metabolism.

Ms Nishreen Santrampurwala (student)

Nishreen completed her Bachelor of Science in India and undertook her Honours studies at Griffith University. She joined the Liver Research Centre in 2011 as a Research Assistant and commenced her PhD in 2012. She is using next-generation genetic sequencing technology to identify novel molecular pathways which contribute to injury in non-alcoholic fatty liver disease

Dr Laurence Britton (student)

Laurence completed his medical degree at the University of Edinburgh, UK and undertook training in Gastroenterology and Hepatology at the Royal Brisbane and Princess Alexandra Hospitals in Brisbane. He is a part-time lecturer within the Greenslopes Clinical School, University of Queensland and a practising Gastroenterologist at Greenslopes Private Hospital. Laurence commenced his PhD in 2012 and aims to determine how iron influences the progression of non-alcoholic fatty liver disease.

Dr Janske Reiling (student)

Janske completed her medical degree at the University of Maastricht, The Netherlands. She joined the Liver Research Centre in 2013 as a PhD Student. She works closely with Professor Jonathan Fawcett from the Queensland Liver Transplant Service and is studying the mechanisms of bile duct narrowing following liver transplantation. This condition often complicates recovery and is difficult to treat.

Dr Terrence Tan

Terrence completed his medical degree at the University of New South Wales before undertaking advanced training in Gastroenterology and Hepatology at the Royal Perth, Sir Charles Gairdner and Freemantle Hospitals in Perth. Terrence completed his PhD in the Liver Research Centre in 2012. He continues to actively participate in research with particular interest in the role of iron in end-stage liver disease as well as the mechanisms of co-toxic liver injury.

Dr Tanis a graduate of the GMRF PhD Scholarship Program.

Dr Amy Sobbe

Amy conducted her undergraduate degree and Honours degree at the University of Southern Queensland. Amy joined the LRC as a research assistant in 2008 and began her PhD in 2009. She examined antifibrotic treatments in models of cholestatic liver disease. Amy now works as Data Manager in the GMRF Clinical Trials Unit.

Dr Sobbeis a graduate of the GMRF PhD Scholarship Program.