DNA discoveries advancing medical research
New target could reduce pancreatic cancer spread
Cancer mutations discovered in so-called ‘junk’ DNA
Welcome
Dear Garvan family,
At Garvan, we ask tough research questions to find better ways to diagnose, prevent and treat disease. Your partnership is critical to helping us answer them.
I’m delighted to introduce this final issue of Breakthrough for 2024 and share with you the latest research updates from the Institute.
A key focus of Garvan this year has been to refine the strategic direction that will let us drive extraordinary science with the power to improve health for all.
This has included recruiting exceptional research talent like Dr Ankur Sharma, who is building on his discovery that cells in the tumour microenvironment undergo similar genomic changes to developing embryos. This groundbreaking research is already progressing a new personalised immunotherapy approach for liver cancer to clinical trials and has potential to lead to vaccines targeting cancer – a demonstration of what is possible when our unique strengths in the fields of cancer, genomics and immunology combine.
Disease touches all of us, and this research would not be possible without your vision. Featured here on page 4 is Phillip, one of Garvan’s generous Partners for the Future, who decided to leave a gift in his Will as an investment in the future of his grandchildren and loved ones.
On behalf of us all at Garvan, I wholeheartedly thank you for your support in making transformative science possible. I wish you a restful and joyous holiday season.
Yours,
Professor Benjamin Kile Executive Director
Our strategy for discovery
In November, the Garvan Institute achieved a significant milestone, with Executive Director Professor Benjamin Kile officially launching Garvan’s Strategic Plan 2025-2028.
The Strategy presents a bold research vision for Garvan, centred around our scientific strengths in cancer, genomics and immunology.
It describes ambitious initiatives and refined objectives that will lead to more innovation in our discoveries, accelerate their translation to the clinic, develop our exceptional research talent and build institutional sustainability that will see the Institute thrive and grow in the decades to come.
Thank you for joining us on this exciting next chapter of Garvan’s story. We look forward to updating you on its progress in our upcoming issues.
To read our Strategic Plan visit: garvan.org.au/strategic-plan
Cover image: Molecular illustration of a nucleosome
Discoveries in Focus
Welcome Dr Ankur Sharma
In June this year, we welcomed Dr Ankur Sharma to Garvan’s Faculty. Dr Sharma brings with him leading expertise in cancer biology and an existing program of clinical translation.
He joined Garvan from the Harry Perkins Institute of Medical Research in Western Australia. Dr Sharma has a unique vision and an ability to foster local and international collaborations, recognised by being awarded the prestigious 2024 CSL Centenary Fellowship to develop mRNA vaccines that target tumour cells.
Dr Sharma says: “I am honoured to join Garvan’s passionate research community to embark on this next exciting chapter of my work. My team is ready to join
Guardians of the immune system
Dr James Cremasco
This image, captured by Dr James Cremasco, offers a rare glimpse at the inner workings of one of our body’s most formidable defenders: the natural killer (NK) cell. These microscopic assassins patrol our bodies, seeking out and destroying virus-infected or cancerous cells using granules full of enzymes.
Measuring about 12 micrometres across – roughly one-tenth the width of a human hair – the cell’s membrane is shown in vibrant orange, forming a protective barrier. Within, the cell’s ‘muscles’ – F-actin filaments – appear in cyan, providing shape and mobility. The magenta spots represent Granzyme B, a protein that acts as the NK cell’s weapon, capable of triggering cell death in its targets.
Finally, the blue coloured areas show Rab27a, a protein crucial for delivering the cell’s deadly cargo. Studying the function of cells helps us learn how they can malfunction, leading to over- or underactive immune responses.
This research is vital for developing treatments for autoimmune diseases and immune deficiencies, as well as cancer immunotherapies.
Garvan’s unwavering commitment to develop the next generation of medical therapies.”
To read more please visit: garvan.org.au/ankur-sharma
Dr Ankur Sharma
DNA Detectives
Phillip’s hope for future generations
Have you ever seen a platypus in the wild? Recently I’ve been involved in a local project to find populations of these elusive monotremes in Hornsby Shire. We sample creek water, searching for DNA fragments to prove their existence. My two young granddaughters help me, despite being just seven and nine. Their fascination with this process warms my heart. We also do educational bushwalks and participate in a live critter’s day, netting lake water to observe tiny aquatic life.
The platypus project reminds me of Garvan’s work. Both
involve looking for something that may be there, could be there, but is hard to spot. Using science to confirm existence is a smart approach. Once you know it’s there, you can focus resources on finding and addressing it.
Recently, I read about the Queensland government using similar technology to test waterways for crocodiles. Another elusive creature, this one seriously dangerous to humans. It struck me how this method of detecting traces of DNA can be applied in different contexts. In fact, Garvan researchers have worked on a similar idea to detect early signs of cancer. By looking for tiny amounts of tumour DNA in blood samples, the goal is to spot cancer early or check how well treatment is working.
Throughout my life, I’ve tried to look forward, to see the next problem or consider a solution rather than a temporary fix. I’ve lost people to incurable illness, which has made me passionate about prioritising prevention in medical research.
Our bodies are complex and react in so many different ways. This is why I believe there should be individual solutions in medicine, not a one-size-fits-all approach. The answers often lie deep in our individuality – we just need to find them.
Garvan’s approach to personalised medicine has inspired me to leave a gift in my Will to support their work. It gives me hope for future generations, including my granddaughters.
Like Phillip, would you consider a gift in your Will? To request our Bequest Giving brochure or for a no obligation conversation, please contact Claire Swinn on (02) 9295 8527 or bequests@garvan.org.au or visit garvan.org.au/bequest
Running with heart
This year’s City2Surf saw an incredible 76 participants join ‘Team Garvan’, raising more than $41,600 in support of our groundbreaking research. A heartfelt thank you to everyone for your support and generosity.
A special mention to our long-time supporters at Belmadar, who once again rallied their team of staff, family and friends to support Garvan’s blood cancer research. The team went above and beyond, exceeding their goal and raising over $31,000!
Belmadar have steadfastly supported Garvan’s research in acute myeloid leukaemia since 2015 in tribute to their late founder Domenico Marrocco.
Support from community champions, like Belmadar, is crucial to accelerating Garvan’s medical research discoveries. You too can make a big difference to medical research by fundraising for Garvan.
If you’d like to participate in a community event, or get your workplace involved, we’d love to hear from you.
To contact us please call (02) 9295 8110 or email community@garvan.org.au
Garvan immunologist receives national recognition
Professor Stuart Tangye, Head of the Immunology and Immunodeficiency Lab at Garvan, has been awarded the prestigious 2024 UNSW Eureka Prize for Scientific Research. This achievement recognises his groundbreaking work in the field of human immunology, which has significantly advanced our understanding and treatment of rare immune diseases.
For over two decades, Professor Tangye has dedicated his career to investigating the mysteries of the immune system. His research has identified new genetic variants linked to rare immune diseases, leading to many diagnoses and targeted treatments. These discoveries have provided hope to those with rare immune conditions and shortened the time it takes for patients to receive an accurate diagnosis.
“Receiving the prize is a humbling honour, and a real thrill, but more importantly, it’s an opportunity to shine a light on rare immune diseases and the patients and their families affected by them. Our work is about improving lives, one gene and one case at a time,” says Professor Tangye.
The Australian Museum Eureka Prizes are among the most esteemed awards in Australian science, celebrating excellence in research, innovation, leadership and communication.
Professor Tangye’s research is supported by John Brown Cook Foundation and The Corio Foundation.
You can give the gift of a longer, healthier life for everyone by supporting life-changing medical research. Donate to Garvan's research on behalf of a friend or loved one and you’ll help support scientists in discovering better treatments for some of the most devastating diseases affecting society today.
We have a range of personalised cards available for the festive season, birthdays, special occasions, and in sympathy including both print at home and virtual cards.
Team Garvan
Professor Stuart Tangye
New target could reduce pancreatic cancer spread
We are one step closer to a breakthrough that could help to reduce the spread of one of the most lethal cancer types.
Microscopic view inside mouse model of pancreatic cancer tumour
The colours indicate different components: Blood vessels Tumour cells Collagen – the connective tissue making therapy penetration challenging
Treating pancreatic cancer is extremely challenging and often comes with a poor prognosis. With a fiveyear survival rate of just 12%, there’s a critical need for innovative treatments to tackle this relentless disease.
Garvan scientists have now identified a molecule called nidogen-2 as a potential driver of pancreatic cancer progression and metastasis. This discovery could pave the way for a promising new treatment approach for the aggressive cancer, which is often resistant to conventional treatment options.
Pancreatic tumours contain a dense scaffolding tissue, which has been a major barrier to treatment and is a key reason behind the cancer’s well-known chemotherapy resistance.
However, the research team, led by Dr Brooke Pereira, found that blocking nidogen-2 can increase the effectiveness of chemotherapy and reduce the cancer’s spread.
“Our findings suggest that lowering nidogen-2 could improve the way we treat pancreatic cancer and lead to significantly less metastasis – which is one of the main causes of death in pancreatic cancer,” says Dr Pereira.
Using an innovative technique called tissue decellularisation, which involves removing all cells from tumour samples while keeping their scaffolding components, the researchers observed that nidogen-2 levels were higher in more aggressive tumours.
blood vessels to deliver chemotherapy drugs into the tumour effectively – it’s one of the biggest challenges in treating pancreatic cancer. By targeting nidogen-2, we were able to normalise the tumour blood vessels,” says Dr Pereira.
“This dual effect of enhancing chemotherapy while also reducing metastasis is really exciting. This suggests that targeting nidogen-2 could be a promising new approach for pancreatic cancer.”
Associate Professor Thomas Cox
They also found that reducing nidogen-2 levels in pancreatic tumours led to decreased matrix density, smaller tumours and improved blood vessel structure –something Dr Pereira believes could make a big difference for those undergoing chemotherapy.
“Tumours with less nidogen-2 had blood vessels that were more open – they were wider and more evenly distributed compared to the collapsed and chaotic vessels usually seen in pancreatic cancer. This caught our attention, because you need functional
The researchers’ next step is to develop clinical approaches to target nidogen-2, such as blocking antibodies that bind to it, and combining this with existing chemotherapy regimens to allow drugs to better penetrate the tumour and kill cancer cells.
In the future, the researchers are also hoping to pair this approach with immunotherapy to further improve outcomes for patients.
“Pancreatic cancer has seen minimal improvement in survival for decades, so we urgently need new tactics,” says Professor Paul Timpson, co-senior author of the study and Head of the Invasion and Metastasis Lab at Garvan.
“We believe targeting the tumour scaffolding through nidogen-2 could be a vital step forward in improving treatment of this aggressive disease.”
This research is supported by Mr Len Ainsworth AM, The Ronald Geoffrey Arnott Foundation, Suttons Motors Management and in memory of Franz Loibner.
Prof Paul Timpson, Dr Brooke Pereira and A/Prof Thomas Cox
The role of DNA knots in advancing cancer research
Garvan researchers map 50,000 i-motifs, revealing their potential in cancer diagnostics and treatment.
When you think about DNA, it’s likely the iconic double helix structure that comes to mind. But not all DNA is so beautifully constructed – sometimes it twists into knot-like formations called i-motifs.
In a groundbreaking study, Garvan researchers mapped 50,000 of these i-motifs in the human genome, shedding new light on their potential significance. These knots are concentrated in regions crucial for regulating genes and are found in areas associated with challenging cancer targets.
“The widespread presence of i-motifs near these ‘holy grail’ sequences involved in hardto-treat cancers opens up new possibilities for new diagnostic and therapeutic approaches,” says Associate Professor Sarah Kummerfeld,
Chief Scientific Officer at Garvan and co-author of the study.
This discovery suggests targeting i-motifs could influence gene expression, potentially expanding current treatment options for cancer patients. I-motifs are unusual structures that protrude from the DNA double helix and are composed of cytosine, one of the four main building blocks of DNA. Cytosine typically pairs with guanine, forming the characteristic rungs of a DNA ladder. But in i-motifs, cytosine binds to itself.
“Our findings confirm that i-motifs are not just laboratory curiosities but widespread – and likely to play key roles in genomic function,”
The knot-like i-motif structure protruding from DNA’s double helix was mapped in 50,000 locations in the human genome
says senior author Professor Daniel Christ, Head of the Antibody Therapeutics Lab and Director of the Centre for Targeted Therapy at Garvan.
The potential of i-motifs in cancer therapy is particularly exciting. “We found i-motifs form in a crucial region of oncogenes – those with the potential to cause cancer,” says Cristian David Pena Martinez, first author of the study. “One example is the MYC oncogene, which encodes one of cancer’s most notorious ‘undruggable’ targets, presenting a new opportunity to target disease-linked genes through i-motif structure.”
Timeline of DNA Architecture
Discovery of DNA
Friedrich Miescher discovers a substance in white blood cells called “nuclein,” later identified as DNA.
Double helix structure
Scientists announce the discovery of the double helix structure of DNA, the molecule containing human genes.
1962
1979
1993
Quadruplex DNA
Scientists discover G-quadruplexes, four-stranded DNA structures that help maintain telomeres and regulate genes.
Z-DNA
Discovery of Z-DNA, a left-handed DNA helix, different from the common right-handed B-DNA.
I-motif DNA
Discovery of the i-motif structure, a four-stranded DNA configuration formed in cytosine-rich regions of the genome.
First human genome published
The Human Genome Project generates the first complete human genome sequence.
I-motif sites mapped
Garvan researchers map over 50,000 i-motif sites in the human genome, showcasing their potential role in gene regulation involved in disease.
A/Prof Sarah Kummerfeld, Prof Daniel Christ and Cristian David Pena Martinez
New class of cancer mutations discovered in so-called ‘junk’ DNA
Using AI, Garvan researchers have found potential cancer drivers hidden in so-called ‘junk’ regions of DNA, opening up possibilities for a new approach to diagnosis and treatment.
According to a recent Garvan study, noncoding DNA – the 98% of our genome that doesn’t contain instructions for making proteins – could hold the key to a new approach for diagnosing and treating cancers. The findings reveal mutations in previously overlooked regions of the genome that may contribute to the formation and progression of at least 12 different cancers, including prostate, breast and colorectal.
“Non-coding DNA was once called ‘junk DNA’ due to its apparent lack of function,” says Dr Amanda Khoury, Research Officer at Garvan and co-corresponding author of the study. “Our research has found mutations in these DNA regions that could open an entirely new, universal approach to cancer treatment.”
Garvan researchers focused on mutations affecting binding sites for a protein called CTCF, which helps fold long strands of DNA into specific shapes.
epigenomic features to predict which CTCF sites are likely to be persistent anchors in a total of 12 cancer types. They then assessed more than 3,000 tumour samples from patients diagnosed with the 12 cancer types and found the persistent anchors were rich with mutations.
“Using our machine learning tool, we identified persistent CTCF binding sites in 12 different cancer types,” says Dr Wenhan Chen, first author of the study.
The discovery could lead to early diagnosis and new treatments effective for many cancer types
“We had already identified a subset of CTCF binding sites that are ‘persistent’ – that is they act like anchors in the genome, present across different cell types,” says Dr Khoury. “We hypothesised that if these anchors become faulty, it could disrupt the normal 3D organisation of the genome and contribute to cancer.”
To test this, the researchers developed a new sophisticated machine learning (AI) tool called CTCF-INSITE, which used genomic and
“Remarkably, we found that every cancer sample had at least one mutation in a persistent CTCF binding site.”
“This research confirmed that persistent CTCF binding sites are ‘mutational hotspots’ in cancers. We think these mutations give cancer cells a survival advantage, allowing them to proliferate and spread,” adds Dr Khoury.
These findings could have broad implications for understanding and treating many types of cancer. “Most new cancer treatments have to be carefully targeted to specific mutations not always common amongst different tumour types, but because these CTCF anchors are mutated across multiple different cancer types, we’re opening up the possibility of developing approaches that could be effective for multiple cancers,” says Professor Susan Clark, Head of the Cancer Epigenetics Lab at Garvan and lead author of the study.
Image: Dr Amanda Khoury and Professor Susan Clark
Dr Venessa Chin Emerging Leaders Prize
Speeding up lung cancer diagnosis
Dr Venessa Chin, a medical oncologist and researcher at Garvan, has been awarded the inaugural Emerging Leaders Prize. The prize, established by young philanthropists excited to support brilliant emerging talent at Garvan, will fund her innovative approach to advancing lung cancer care.
Dr Chin’s project aims to streamline the cancer diagnostic process, potentially reducing the time from biopsy to diagnosis from weeks to days. Her method centres on Xenium, a cutting-edge technology capable of analysing hundreds of cellular markers simultaneously.
“Current diagnostic procedures often require multiple biopsies and sequential tests, which can be distressing for patients and delay treatment,”
Dr Chin says. “We’re working to develop a spatiallybased method that could provide comprehensive diagnostic information from a single tissue sample.”
The proposed technique would combine standard pathology with molecular and genomic analyses in one step. If successful, it could significantly reduce the need for repeated biopsies and accelerate commencement of treatment.
Dr Chin’s research has broader implications beyond lung cancer. “While we’re starting with lung cancer, this approach could potentially transform diagnostics for various cancer types,” she adds.
From loss to legacy
When I lost my beloved wife to liver cancer in 2017, it started me on an unexpected journey. As a senior lawyer accustomed to navigating complex cases, I found myself charting a course through indescribable personal loss towards a broader purpose: advancing medical research.
Now semi-retired, I see my monthly donations and legacy gift as an investment in the future of my children and loved ones, as well as mankind at large.
This commitment has taken on further meaning as I’ve faced my own health challenges – prostate cancer and a critical heart condition – and thanks to medical science, received innovative treatments that returned me to virtual normality.
Witnessing Garvan’s expansive work in human biology firsthand during research facility tours has reinforced my resolve. By supporting their efforts, we’re not merely funding a lab; we’re creating a healthier landscape for Australians and beyond.
I invite others to join this endeavour. In honour of our loved ones, we can bring about the discoveries that will reshape medicine’s future.
Would you consider joining us as a Partner for Discovery? Please visit: garvan.org.au/support-us/monthly-giving
Jewellery with purpose
Since 2016, Paspaley has shown unwavering support for Garvan’s cancer research. They generously contribute 20% of the proceeds from each Kimberley bracelet sale. The collection combines hand-selected Australian South Sea Pearls with regional, renewable, aromatic sandalwood for a wearable, timeless style.
To give a gift that means more this holiday, please visit: garvan.org.au/paspaley
Dr Venessa Chin
David, Partner for Discovery
