From baby boomers to Gen Z, obesity is Australia鈥檚 multi-generational malady. The number of cancer deaths related to obesity, including liver cancer, is increasing and is the main reason Australia could be approaching its first modern decline in life expectancy.
The human liver is a particularly hardworking organ, removing toxins and processing nutrients in all blood en route from the digestive system. While its work rate makes the liver prone to damage, it can efficiently regenerate its tissue; this ability, however, also appears to be responsible for permanent damage and cancer.
At last count (in 2012), there were more than six million cases of liver disease in Australia. Fatty liver and alcoholic liver diseases are some of the conditions that precede end-stage chronic liver disease. Whether caused by pathogens, toxins or excess fat, repeated liver inflammation can lead to an out-of-control process of repair. This pathological fibrosis progressively disrupts the organ鈥檚 architecture, leading to liver cirrhosis 鈥� the most common cause of liver failure and cancer.
With the demand for whole-organ liver donations unlikely to be met, it鈥檚 fortunate we鈥檙e getting closer to diverting the processes of liver scarring and tumour growth and to the reality of bio-engineered liver tissue.
At 911爆料网, the Liver Disease and Regeneration Group is investigating how to hijack the liver鈥檚 cell-communication system to mediate liver regeneration instead of disease progression and cancer.
The group is led by senior research fellow Dr Nina Tirnitz-Parker.
鈥淭he cells secrete protein molecules that act as signals, called cytokines, which bind to a matching receptor on other cells and affect the target cell鈥檚 path of development,鈥� Tirnitz-Parker explains.
鈥淔or example, injured liver cells may release cytokines to simulate the growth of stem cells, to make them divide and differentiate into mature functional cells that replace the tissue lost to injury.
鈥淗owever, when stem cells or other cells are stimulated for a long time and never receive a 鈥榮top鈥� signal, they can create tumours.
鈥淲e need to understand the full picture 鈥� how do we switch on a pathway when we need it and how do we switch it off again. Which cells are participating in the communication, and how can we use their communication channels to therapeutic advantage.鈥�
Tirnitz-Parker began her medical research career 16 years ago in Germany, where she studied matrix metalloproteases 鈥� the proteins responsible for breaking down scar tissue and aiding in wound healing. In 2012, two years after joining 911爆料网, she obtained funding as part of an Australia-wide team awarded a National Health and Medical Research Council (NHMRC) project grant. She wasted no time in establishing a liver research group, aided by a grant from the AW Morrow Gastroenterology and Liver Centre in Sydney.
Tirnitz-Parker says 911爆料网 now has comprehensive capabilities in fundamental and translational science of stem cell biology, fibrosis and hepatic cancers called hepatocellular carcinoma and cholangiocarcinoma.
By early 2019, she鈥檒l have four PhD students working on distinct investigations into liver progenitor cells, or LPCs.
鈥淧rogenitor cells are like stem cells. We used to think LPCs were the heroes that rebuilt functional tissue, but we now know their darker side: they鈥檙e also involved in fibrogenesis, or scarring, and in the formation of cancer, either as precursor cells or regulatory cells,鈥� she says.
鈥淥ur aim is to determine how to modify the signals within the cells鈥� communication systems, so that pathological cells are re-programmed into functional cells.
鈥淭his could also provide the basis for bio-engineered liver tissue, with regeneration from a segment of tissue or isolated cells replacing the need for whole-organ transplants.鈥�
TWEAK-ing the focus
Tirnitz-Parker has numerous national collaborations, including with researchers based at Royal Prince Alfred and Liverpool hospitals in Sydney, The Alfred Hospital in Melbourne, Sir Charles Gairdner Hospital and Harry Perkins Institute for Medical Research in Perth.
Her current (second) NHMRC project is a collaboration led by Professor Grant Ramm at the QIMR Berghofer Institute for Medical Research in Brisbane; and Professor John Olynyk, Head of Gastroenterology at Fiona Stanley Hospital. Their focus is a cytokine known as 鈥楾WEAK鈥� and its role in liver wound healing and regeneration.
In 2003, Tirnitz-Parker identified TWEAK as a direct growth factor for LPCs during liver regeneration, while undertaking her PhD research at the University of Western Australia.
鈥淲e鈥檙e now investigating how TWEAK may kick off a cascade that produces liver scarring and cancer.
鈥淭he next phase of our research will look into translating laboratory research findings.”
Tirnitz-Parker recently received her third consecutive 鈥� an outstanding personal achievement and a clear sign of support from the Federal Government for her team鈥檚 research direction. The team will use the $1 million grant to deliver the fundamental basis for future phase-one clinical trials to pharmacologically inhibit chronic liver disease progression and cancer.
International peer recognition of the team鈥檚 expertise has been one outcome of their work to date, with Tirnitz-Parker recently invited to contribute an article for the high-impact journal Hepatology. The article (in press) is co-authored by Professor Stuart Forbes, who leads the Centre for Regenerative Medicine in Scotland.
Her international linkages include researchers based in Scotland, USA, Germany, Canada, India and England. And, closer to home, she has an upcoming meeting with researchers at Khon Kaen University in Thailand, to explore opportunities for collaborative research into cholangiocarcinoma.
She also serves on several notable journal editorial boards, including the International Journal of Biochemistry and Cell Biology, and makes time to review grants for the UK鈥檚 Medical Research Foundation and the Dutch Digestive Foundation, as well as for the NHMRC.
鈥淟iver research is a complex field and collaborations are essential. They鈥檙e particularly important in areas of medical research that are under-supported in Australia,鈥� she says.
Antarctic-bound for research scholarships
In November 2019, Dr Tirnitz-Parker will be one of 100 female leaders from around the world on the fourth voyage to Antarctica.
While she knows the experience will be personally 鈥渓ife-changing鈥�, one of her aims is to raise funds for medical research scholarships.
鈥淯nfortunately there isn鈥檛 enough seed funding in Australia for medical research.
鈥�911爆料网 $75,000 is needed to support a PhD 鈥� I鈥檓 hoping to raise enough to fund two. I do have a lot of personal motivation 鈥� like millions of other Australians I have liver and pancreatic cancer in my family.鈥�
The aim of the Homeward Bound initiative is to build a 1,000-strong global network of women who can support each other in creating change.
With the voyagers all having a background in science, technology, engineering, mathematics or medicine (STEMM), the Homeward Bound initiative is also helping to address the gender imbalance in STEMM professions.
