Groundbreaking personalised medicine research projects have been launched at Garvan with $10 million in highly competitive federal grants. The four grants will enable researchers to investigate tailoring treatments based on individual molecular profiles in diseases like cancer and autoimmunity, thanks to National Health and Medical Research Council funding announced today by Mark Butler, Minister for Health and Aged Care.
The five-year grants foster creative and pioneering research by giving recipients the opportunity to establish new innovative programs that explore emerging research ideas.
The researchers aim to observe immune cells transforming inside the body to understand how immune responses go awry; trace how tumours evolve to refine drug combinations using data integration; investigate cancer’s epigenetic code to combat drug resistance and provide new cancer biomarkers; and develop therapies targeting the specific origin of autoimmunity in patients.
The Garvan projects awarded will commence in 2024 and are all in the Leadership category, reserved for the nation’s foremost researchers tackling major health challenges.
Professor Benjamin Kile, Executive Director of the Garvan Institute, commended the recipients on their success.
“Receiving funding for these projects is a resounding validation of the high-impact work done at Garvan, backed by scientific excellence and world-leading capabilities. More importantly, it represents hope for the millions of people impacted by the diseases our scientists are investigating and addressing,” he says.
Personalised autoimmune disease treatment – Associate Professor Elissa Deenick
Associate Professor Elissa Deenick is spearheading an innovative approach to treating autoimmune diseases, conditions where the body’s immune system mistakenly attacks its own cells – such as systemic lupus erythematosus and thyroiditis. Her goal is to develop personalised therapies that specifically target the origin of someone’s disease, rather than just treating the symptoms and non-specifically suppressing the immune system.
To achieve this, Associate Professor Deenick is developing methods to identify the precise mechanisms behind individual cases of autoimmunity. “By pinpointing the specific drivers of disease in each person, we can tailor treatments to block them directly. This not only improves overall outcomes but also minimises the significant side effects often associated with the standard treatment of immunosuppression,” she says.
The grant will enable Associate Professor Deenick to study the cellular and molecular signatures of autoimmune pathology, leveraging her expertise studying rare diseases of immune dysregulation, known as inborn errors of immunity. Using both advanced multi-omics techniques to analyse patient cells and tissues and bespoke mouse models, she aims to find the drivers of disease in each patient by identifying dysregulated cellular, molecular and metabolic pathways.
As well as advancing autoimmune treatment, Associate Professor Deenick’s transformational project has the potential to bring new insights into the nature of immune diseases themselves, potentially leading to new avenues for prevention.
“In our research, my team is driven to find more effective care for those living with these serious conditions. Understanding heterogeneity – differences between patients – is the key,” she says.
Insights into immune cell fate – Professor Tri Phan
Professor Tri Phan has received a grant to image immune cell interactions as they unfold in the dark spaces deep inside the body’s tissues. His team will used advanced intravital microscopy to capture footage of B cells and other immune players ‘talking’ to each other in real time. This will provide insights into how these cell-cell communications and interactions determine the cell’s fate – for example, whether to remain at rest, or be triggered into becoming an antibody-secreting plasma cell. By understanding the hidden molecular conversations between cells, they hope to elucidate how pathogens, cancers or autoimmunity arise.
“We’ve pioneered techniques to film immune cells deep in living tissues and organs at the ACRF INCITe Centre at Garvan. Now we will map out the signals and contacts between cells that decide their destiny, controlling whether they become activated or suppressed. Using this knowledge from witnessing immune activity live, we can steer cells to prevent disease,” says Professor Phan.
Mapping out the signals from these cells in their niches could reveal why immune responses sometimes go awry, inducing autoimmune attack or allowing cancer growth. By providing insights into our immune system’s inner workings in action, Professor Phan will identify some of the key controllers of immune cell destiny. The ability to influence immune cell fate could transform our approach to fighting infection, preventing cancer, stopping autoimmunity and even repairing weakened bones.
“This precision control will enable a new generation of tailored immunotherapies, vaccines, cancer and autoimmunity treatments,” says Professor Phan.
Understanding cancer’s epigenetic code – Professor Susan Clark
Professor Susan Clark is pushing new frontiers in cancer research by investigating the powerful role of epigenetics in driving cancer. While genetic mutations are recognised as key players in cancer development, epigenetics – changes that control how genes are expressed – also play a major role, yet remain less understood. Professor Clark’s project will use advanced sequencing technologies to explore how alterations in the 3D structure of the ‘epigenome’ – the layer of instructions that organises and regulates DNA’s activity – can lead to harmful gene activity within cancer cells. A major aim is understanding the epigenetic rewiring that enables the development of resistance to therapies like hormone treatments in breast and prostate cancer and that can be used for new biomarkers to detect cancer relapse.
Building on her expertise in studying how the epigenetic code gets scrambled in cancer cells and alters gene activity in harmful ways, Professor Clark will make use of cutting-edge CRISPR gene editing and single-cell sequencing techniques.
“We’ve made great progress decoding cancer genetics over the past decades, but the role of epigenetics remains more enigmatic,” says Professor Clark. “Now we have new tools at our disposal to deeply understand how genetic and epigenetic changes interact in cancer, and their consequences.”
Her vision is that within five years, we’ll have a richer grasp of this key dimension of cancer biology to translate into more effective, targeted drug combinations based on epigenetic therapies, and better monitoring of disease using epigenetic biomarkers.
Can data integration be harnessed against pancreatic cancer? – Associate Professor Marina Pajic
Associate Professor Marina Pajic is pioneering precision medicine-guided therapies to treat pancreatic cancer, one of the deadliest cancers. The five-year survival rate is currently just over 12%, but the tumours vary on a molecular level, suggesting carefully tailored treatment combinations based on each cancer’s profile could be more effective.
“We’re using the latest single-cell sequencing technologies to analyse deep tumour molecular characteristics and using this knowledge, match patients with the optimal therapies for them,” says Associate Professor Pajic.
“The volume of complex data generated by these new technologies requires detailed validation of any findings. Our established preclinical pipelines allow us to do exactly this, to create precision medicine-guided treatment approaches that will make a real difference in the clinic, giving patients a better chance,” she says. “Within five years, we aim to increase access to new, promising therapeutic approaches for patients with pancreatic cancer, and enable monitoring of treatment response in real-time. This will lead to effective identification of treatments and biomarkers, providing a roadmap to improved patient survival.”
Associate Professor Pajic is a leader in pancreatic cancer research, unlocking the potential of precision medicine to address this challenging disease.
Associate Professor Elissa Deenick is a Scientia Associate Professor at UNSW Medicine & Health. Professor Tri Phan and Professor Susan Clark are Conjoint Professors at St Vincent's Clinical School, UNSW Medicine & Health. Associate Professor Marina Pajic is a Conjoint Associate Professor at St Vincent's Clinical School, UNSW Medicine & Health.