Kolling Institute NEWS
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Our teams leading the fight against diabetes
New approach to identify those with silent heart disease
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Researchers to support upcoming space missions
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Northern Sydney Local Health District
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MESSAGE FROM THE ACADEMIC DIRECTOR
As you look through this newsletter, I hope it will give you a clear picture of the scope of research currently underway at the Kolling Institute, and its impact on how care is delivered in hospitals and in the community. With our focus on high-quality, translational research, our work is increasingly informing models of care and crucially, our understanding of particular conditions. It is pleasing to see the range of activity throughout the Kolling in each of our priority research areas. Our researchers are making considerable progress in their investigations into musculoskeletal conditions, heart and kidney disease and in the fields of neuroscience and pain. All these areas present a significant challenge for the community, and with an ageing population, we expect the challenges will only increase. That’s why it’s so important our researchers are at the forefront of progress and improved standards of care, and that they are supported with a robust strategic framework. We have made good inroads in the last 12 months implementing the Kolling Research Plan and I’m pleased to report that the key goals are being met from increased funding to better health outcomes and greater collaboration. Our researchers are increasingly working with national and international
peers, and operating within a diverse research ecosystem including our health and university partners, and industry representatives. Our researchers are also being supported with new infrastructure and in recent months capabilities were strengthened with the installation of $750,000 of new high-tech equipment. This substantial investment will enable our cancer and neuroscience teams to undertake research they simply couldn’t do before, and provide them with valuable information about how cells function in disease and health. This vital information will inform a new approach. In the last few months, the Kolling continued to host a range of specialised events, including a Space Colloquium involving some of the brightest minds in Australia’s space medicine community. This was a successful event and one which we expect will lead to a greater focus on research to support future missions in space. Pleasingly, we have seen increasing engagement with our Kolling Seminar Series, which have featured leading Australian and international presenters. The seminars offer an opportunity to hear the very latest research progress in a specific area, and it’s encouraging they are being well attended.
A busy schedule of upcoming events is planned including the Kolling Symposium on November 23rd at the Northside Conference Centre. Planning is also underway with the NORTH Foundation, local Rotary clubs and the Ku-Ring-Gai Stealers Softball/Baseball Club for a Hit-A-Thon on March 3rd 2024 to raise awareness and funds for road safety research initiatives. It was lovely to meet with the family of the late Bill Walsh during a recent visit to the Kolling. Bill was one of the first people to undergo chemotherapy at Royal North Shore Hospital and he raised a remarkable amount of funding to establish the Bill Walsh Cancer Research lab many years ago. His legacy continues to help those today and I would like to thank his family for their continued interest in our life- saving work. I would like to take this opportunity to welcome Adjunct Professor Anthony M. Schembri AM to his new role as Chief Executive of the Northern Sydney Local Health District. We look forward to working closely with him and building on our culture of research excellence and improved wellbeing. Read on to learn more about the latest focus for our researchers and their efforts to lift the standard of care we all receive.
Professor Jim Elliott
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KOLLINGNEWS | SEPTEMBER 2023
Researchers saving those with silent heart disease
For many years we’ve understood that heart disease is linked to unhealthy habits and underlying health issues, but our researchers at the Kolling Institute are pioneering a new approach to identify and treat those with the disease without the traditional risk factors. In Australia, a heart attack occurs every nine minutes, often with a tragic outcome or lifelong consequences. Many of these attacks are associated with smoking, high blood pressure, diabetes and high cholesterol, where arteries have been damaged and obstructed by plaque. But our researchers are turning their focus to a group of patients who have developed silent cardiovascular disease, without any warning signs. This group accounts for an alarming 25 per cent of people who have had a heart attack without any of the standard modifiable risk factors. Internationally recognised researcher and Royal North Shore Hospital interventional cardiologist Professor Gemma Figtree said we’ve seen an increase in patients like this over the last 10 years, and worryingly, many fared poorly after initial hospital treatment. “A greater number of them died within 30 days of the initial heart attack compared to patients with traditional risk factors, and women were disproportionately affected,” she said. “This group has until now, not been the focus of research or disease management, but we are working to gain a better understanding of how the disease develops in these patients and how we can capture them early and save lives. “It’s estimated 1.3 million people worldwide die each year due to heart attacks without the usual risk factors.
Professor Gemma Figtree
These patients have no current way of accessing effective treatment for their underlying plaque as it silently develops.” In response to these challenges, Professor Figtree is spearheading a new approach and working with physicians, scientists and industry experts to support this group. Researchers are developing a series of blood tests to identify biomarkers of the underlying disease itself in its silent phase, and confirm whether they point to potential new therapeutic targets. They say if a marker could identify even 50 per cent of people with plaque independently of the risk factor profile, it would allow intervention with effective treatments that stabilise plaque and dramatically reduce the number of heart attacks. Professor Figtree said this will be a crucial step forward, revolutionising heart attack prevention.
“Most current medications for heart disease target the known risk factors like high cholesterol and high blood pressure, however we are working to develop medications which could benefit all those at risk of heart disease, not just those with the obvious risk factors,” she said. “It’s important that this cohort, which has been largely invisible until now, is given the focus they need. “We know the development of new drugs can take many years, but we’ve seen with the success of the COVID-19 vaccines that progress can be made in a short period of time, and we’re convinced that by bringing together the best minds from across the globe, we’re in a strong position to effect change and reduce preventable deaths.”
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Kolling researchers leading the fight against diabetes
With a concerning rise in the number of people developing Type 2 diabetes, our researchers at the Kolling Institute are offering an effective way forward to reduce the impact of the serious disease. Type 2 diabetes is the fastest growing chronic disease in the world, and if the current trend continues, it’s anticipated close to three million Australians will have the disease by 2025. It often occurs in those who are over 40, overweight or if there’s a genetic predisposition, but increasingly doctors are seeing young adults and adolescents with the condition. Sadly, many people may have the disease, and not realise it until the condition is well advanced. Kolling researcher and Royal North Shore Hospital endocrinologist Associate Professor Sarah Glastras said Type 2 diabetes is a crippling condition which can increase your chance of kidney failure, heart attack and stroke. “There is no cure but it can be put into remission with lifestyle changes, with evidence suggesting that losing weight can help you manage your diabetes and return to normal blood sugar levels,” she said. “It is an encouraging time with a range of new drugs, innovations and clinical trials in the pipeline which will offer tools and strategies to manage diabetes. “In the next 12 months, there will be new combined medications which we expect will help with weight loss and the maintenance of glucose levels. “These drugs will have the potential to halt the march of diabetes.”
Professor Sarah Glastras
For many people a combined approach of exercise, diet and medication will achieve significant results. “I often tell my patients you can’t change your age or your genes, but we do have control over what we eat and how much exercise we do. Exercise is crucial to improving the body’s metabolism.” “Importantly, there also needs to be greater access to these promising new medications, and a greater focus on the condition.
“Unlike cancer and heart disease, diabetes often doesn’t receive the attention and funding it deserves. There is a stigma associated with obesity and diabetes, a belief that people have brought it on themselves, neglecting the fact that it is a genetically driven disease.”
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KOLLINGNEWS | SEPTEMBER 2023
Professors Jim Elliott, Gordon Cable, Julie Hides and Dr John Cherry
Australian researchers uniquely positioned to support upcoming space missions
The expertise across Australia’s space medicine community was showcased during a special event co-ordinated by the Kolling Institute and the Australasian Society of Aerospace Medicine. Staged over two days, the colloquium involved national and international experts including representatives from the Australian Space Agency, the CSIRO and Boeing.
“Australian clinicians and researchers have been collaborating with international space agencies for years, with some of our research focusing on clinical advances for astronauts. “Our technological sector is also well placed to offer specialised support, with a track record of innovation. “Australian experience has driven advances in radiation protection, wearable sensors and compression suits worn by astronauts to limit the musculoskeletal effects of microgravity.” Dr John Cherry, a director from the Australasian Society of Aerospace Medicine said Australia is in a strong position to support long duration human spaceflight missions. “We are world leaders in rural and remote healthcare, with experience delivering care in some of the most extreme and isolated environments on earth,” he said. “The Australian Antarctic Program for example has developed specialised training and technology to enable a
generalist doctor to provide medical, surgical, anaesthetic and dental care to an isolated team. “Many of the challenges faced in these settings will be experienced by astronauts and space agencies as human spaceflight extends further into space.” Professor Elliott said the Australian space medicine community is keen to see the medical progress as a result of the upcoming space explorations. “It’s anticipated that some of the lessons learned in space will deliver benefits back on earth and help to drive improvements in health outcomes. “For instance, the new knowledge around the deconditioning of astronauts in space could help doctors managing patients with deconditioning after long periods in hospital.”
Presenters discussed the specific medical, dental, and
psychological needs of astronauts, Australian-designed space suits and opportunities for our space community in NASA’s exploration of the moon and ultimately Mars. Kolling Academic Director Professor Jim Elliott said Australia’s involvement in the Apollo Moon landings is well documented, but perhaps what is not well known is the experience in Australia’s contemporary space industry. “We have a tremendous depth of medical, technological and research expertise in this field,” he said.
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Caitlin Fenech, Dr Karin Aubrey, Dr Neda Assareh and Dr Yo Otsu
New approach delivers breakthrough for pain researchers
Researchers at the Kolling Institute have made important progress towards the development of new treatments for chronic pain by identifying a small group of cells which can control pain responses. The breakthrough comes as approximately 20 per cent of the world’s population suffers from chronic pain, including around 3.4 million Australians. Dr Neda Assareh, a neuroscientist research fellow from the Pain Management Research Centre said medications and psychological support offer some relief, but many people continue to experience ongoing pain without effective treatments, and this often leads to depression and anxiety. She says a large number of people continue to use opioids which can be addictive and ineffective. “Our team however, has been working to develop better and safer treatments for chronic pain by improving our understanding of which pain pathways shape the experience of pain,” she said.
“In this ground-breaking study, we used an advanced bioengineering technique to investigate how the brain organises pain signals, and we found evidence that a never- investigated cell type can control pain. “The study relied on chemogenetics, a technique that allowed us to activate and inactivate a small population of glycinergic neurons in isolation. “These neurons are found in the midbrain periaqueductal gray, a part of the brain which influences pain responses and anxiety linked to pain. “Our study is the first to investigate the role of these neurons in setting pain thresholds, and we found that inhibiting the activity of the glycine- PAG neurons reduced pain responses in both sexes. “It was important to test responses with both sexes as we know that pain affects men and women differently.” Senior researcher Dr Karin Aubrey has welcomed the discovery of this unique group of cells which control pain responses.
“Importantly, there are only a small percentage of these neurons in the midbrain, so by targeting these cells we may be able to develop medications which reduce pain with fewer side effects than existing medicines,” she said. “In the next stage of the program, we will aim to determine how glycine- PAG neurons communicate with higher brain areas, and investigate their ability to alter pain and anxiety outcomes in chronic pain models.” “Our findings are the result of a strong collaborative effort involving senior researcher Yo Otsu, PhD student Caitlin Fenech, and lab assistants Nazim Uddin and Rebecca Power.” The project was made possible with the support of the Ernest Heine Family Foundation and the Pain Foundation. The research has been published in the leading scientific journal eNeuro.
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KOLLINGNEWS | SEPTEMBER 2023
Dr Jun Li and Professor Mark Molloy
Technology giving our researchers the edge Impressive new infrastructure at the Kolling Institute is set to drive progress with our research into cancer and neuroscience.
has welcomed the new technology, saying it will allow researchers to profile gene and protein expression in specific cells of complex tissues such as tumours, brain tissue, liver and kidney cells. “This will in turn, provide valuable new information about how cells function in disease and health,” he said. “It’s wonderful to have this equipment which will help us understand how disease develops. “It will also help us identify new biomarkers indicating which patients are likely to respond to some treatments. “This is important as we continue to see a rise in the number people diagnosed with some cancers. “For example, we are seeing an increase in those under 50 with early onset colorectal cancer, and by 2030, we expect one in 10 cases will be under 50 years old.
“This is a concerning trend, with no clear explanation for the rise in these cases. “A decade ago there was little attention given to this condition, but we now have evidence of increased diagnosis in young people, who sadly, often present with aggressive, advanced disease where treatment options are more limited. “Colorectal cancer is certainly no longer only a disease of the aged.” Bowel cancer research fellow Dr Jun Li has welcomed the opportunity to use the new equipment. “It’s encouraging to have access to these new platforms as it’s allowing us to do research that we simply couldn’t do before,” she said. “This we hope, will lead to a greater understanding of disease, prevention and improved treatment options.”
The equipment includes a digital spatial profiling system, which is regarded as one of the most exciting technological advances globally in the investigation of tissues. The $525,000 instrument has been made possible following a LIEF grant through the Australian Research Council to Professor Mark Molloy. Co-funding was provided by the University of Sydney and Macquarie University. A new laser capture microscope has been installed at a cost of $250,000. This microscope allows researchers to capture specific tissue regions for sequencing and analysis. It was funded by the Ian Potter Foundation, the Kolling and the University of Sydney. Professor Mark Molloy, Lawrence Penn Chair of Bowel Cancer Research
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Research questions the value of injectable medications for osteoarthritis
Our researchers at the Kolling Institute are encouraging those with osteoarthritis to rely on treatments with a proven track record and avoid quick fixes without the data to show they work. The comments follow a steady rise in osteoarthritis cases nationally, with around three million Australians now living with the condition, and many forced to retire early. The rise in cases has coincided with strong interest in injectable medications, particularly for knee osteoarthritis, such as hyaluronic acid, stem cells and platelet-rich plasma. But Royal North Shore Hospital rheumatologist and world leading osteoarthritis researcher Professor David Hunter said we don’t have the data to show these injections work. “The hyaluronic acid injections are no better than a saltwater injection, but they will cost you a lot more, while we just don’t have good enough evidence for the stem cell injections or the platelet-rich plasma,” said the Kolling Institute researcher. Professor Hunter is disappointed that the latest evidence on treatments is not filtering through to consumers and new resources are not reaching those with osteoarthritis. He would like to see a stronger focus on the core treatments which work. “Individuals with osteoarthritis need to be encouraged to manage their condition using behaviour and lifestyle interventions in the knowledge that the development of disease-modifying drugs might still be some way away,” he said.“Some of the evidence-based treatments
Professor David Hunter
include doing exercises that strengthen the muscles around the affected joint. “We recommend working with a physiotherapist or an exercise physiologist trainer to learn how to strengthen those muscles.” Professor Hunter said staying active and losing weight, if you are carrying extra kilos, are also important steps that can make a difference. “We know that losing five per cent of body weight can improve joint pain and function by 30 per cent. This can have a significant impact.”
Research indicates cortisone injections can be used for short-term relief but not a long-term solution. “One injection may be fine but repeat steroid injections appear to increase the risk of progressing the disease,” he said.
Professor Hunter’s views were published in Nature Reviews Rheumatology.
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KOLLINGNEWS | SEPTEMBER 2023
Back pain cases to rise sharply A new study by researchers at the Kolling Institute estimates more than 800 million people will be living with low back pain by 2050, a 36 percent increase from 2020.
Lead author Professor Manuela Ferreira from Sydney Musculoskeletal Health said our analysis paints a picture of growing low back pain cases globally, putting enormous pressure on our healthcare system. “We need to establish a national, consistent approach to managing low back pain that is informed by research,” she said. “Currently, how we have been responding to back pain has been reactive. Australia is a global leader in back pain research, so we can be proactive and lead by example on back pain prevention.” Senior author Professor Lyn March said we know that most available data comes from high-income countries, making it sometimes hard to interpret these results for low to mid-income countries. “We urgently need more and accurate data from countries of low to mid-income,” she said. Co-author Dr Katie de Luca, from CQ University, said if the right action is not taken, low back pain
The prediction follows an analysis of 30 years of global health data from over 200 countries. Modelling shows the number of back pain cases globally will rise to 843 million people by 2050, while in Australia, it’s expected there will be a 50 percent increase. The biggest jump is likely to be seen in Asia and Africa. Researchers are concerned the trend will only get worse with an inconsistent approach to back pain treatment. They say many commonly recommended treatments have been found to be ineffective, including some surgeries and opioids. Researchers say there’s also a misconception that low back pain mostly affects adults of working age. This study shows that most low back pain cases affect older people, and more women than men.
Professor Manuela Ferreira
can become a precursor to chronic health conditions such as diabetes, cardiovascular disease and mental health conditions, invasive medical procedures, and significant disability.” The study analysed global health data from 1990 to 2020. It is the first study to inform modelling for the future prevalence of back pain. The findings have been published in the Lancet Rheumatology.
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Sam Hefferan and Dr Kenji Fujita
Travel opportunities creating new partnerships Funding from the Skipper Jacobs Charitable Trust has helped a group
“It was a great opportunity to build international collaborations and promote our translational research at the Kolling. I really appreciate this travel grant,” he said. Another researcher to benefit from the travel grant was Samantha Hefferan from the Murray Maxwell Biomechanics Laboratory. Sam visited the University of Auckland, where she was able to use the lab’s high-tech imaging methods to explore the ultrastructure of human tendons, and the impact of disease and injury. “I valued every moment of my three months in New Zealand. I was challenged every step of the way with both my research and living in an unfamiliar environment,” she said. “I gained a lot during my time, not only learning new technical skills but also understanding more about the complexity of independently planning and developing tailored protocols for my research questions.”
“On top of strengthening our collaboration with research groups at the University of Auckland, I now have the knowledge-base to bring the practical components of planned collaborative projects closer to home for future research students at the Kolling Institute.” Academic Director Professor Jim Elliott thanked the Skipper family for their financial backing of the trust, as well as the NORTH Foundation for their support of the travel program. “It has been instrumental in helping individual researchers, raising the international profile of the Kolling Institute and contributing to crucial research progress.” If you would like to support our researchers, please donate through the NORTH Foundation.
of our young research leaders broaden their experience and establish new collaborations.
Close to $40,000 was shared amongst five early-to-mid career researchers, allowing them to travel nationally and internationally to progress their research and develop new skills. One of those to receive funding is Dr Kenji Fujita, an early-career pharmacist with a PhD working in the Ageing and Pharmacology Research Group at the Kolling Institute. Kenji helped develop techniques to calculate the frailty index in older hospitalised patients, while also leading research into the quality of pharmaceutical care. During his trip he led a three-day workshop in Denmark, visited collaborators in Norway and delivered a presentation in Japan, a country with the highest proportion of older adults in the world.
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KOLLINGNEWS | SEPTEMBER 2023
The family of the late Bill Walsh during a visit to the Kolling to meet with researchers
Act of generosity continues to deliver hope for those with cancer
The Kolling Institute hosted a special visit by the family of the late Bill Walsh who donated vital funds to establish a cancer laboratory within the institute. His family, including his wife, daughters and grandchildren visited the lab to maintain their strong ties with the research team and meet with Academic Director Professor Jim Elliott. Established in 1980, the Bill Walsh Cancer Research Laboratory now has more than 20 members driving progress in pancreatic, lung, ovarian, Mesothelioma, brain and breast cancer research.
Bill Walsh was diagnosed with terminal cancer in 1975 and was one of the first people to be treated with chemotherapy at Royal North Shore Hospital. During his treatment, he discovered that funds for cancer research at the hospital were very low. He was frustrated with the lack of hope for those with cancer and wanted his two young children to have a better chance of survival if they developed cancer later in their lives. Determined to raise money for a cancer research unit, he organised the Bill Walsh Art Union, where he raised almost $500,000. It was the most successful art union to date and the largest single donation to the hospital at the time. Bill Walsh died in 1979 and didn’t see the realisation of his dream, the Bill Walsh Cancer Research Laboratory which had been made possible as a result of his efforts. Professor Elliott said Bill was an inspiration and one of the great pioneers of fundraising for cancer research.
Bill Walsh
“His courage in the face of adversity led to hope for many people with cancer,” he said. “I would like to thank Bill Walsh’s family for taking the time to visit the Kolling and the cancer research lab, and I’d like to encourage other families to consider supporting our crucial translational research.” Royal North Shore Hospital Director of Oncology and cancer specialist Professor Nick Pavlakis also thanked Bill Walsh’s family, saying Bill’s contribution has had lasting benefits. “The Bill Walsh lab has been an important asset not just in integrating the Royal North Shore Hospital clinical teams with lab based research activity, but in introducing many young cancer specialists to lab and translational research, putting many on the path of ongoing cancer research careers.”
The team is at the forefront of discovery, respected for its
contribution to our understanding of specific cancers and improvements in care. Professor Elliott said the visit by Bill Walsh’s family provided the chance to highlight the impressive team and the state of the art facilities. “It also gave us the opportunity to remember Bill Walsh’s extraordinary efforts raising funds for research and those experiencing cancer,” he said.
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