Taking science to the next generation

For 25 year old, Shalini Guleria, science presents a world of curiosity and opportunity. It is this outlook that has led her to the position of PhD candidate at ONJCRI, while also pursuing ways to bring the magic of science to young children.

At the ONJCRI, Shalini’s research is focused on understanding the role of adipose tissue, or fat, in mammary gland development and also in breast cancer progression.

As part of the Cancer Single Cell Genomics Laboratory, Shalini explains that she is, “using a range of innovative techniques to explore this area and understand the underlying mechanisms in relation to cancer”.

As well as completing her PhD, Shalini is also the founder of a social enterprise called Science Box, which started in late 2018 in New Zealand. The aim of Science Box is to empower children to be involved in science.

“I know that there are so many children out there aged between 5 and 12 who fear science,” says Shalini.

“This was confirmed when I heard a young girl say science was too hard, mostly for boys and you had to be super clever to do it,” she said.

Her vision is to empower children of all ages, socioeconomic backgrounds and demographics to enjoy the magic of science. Science Box aims to explore different science concepts in engaging ways while using household items.

In recognition of her outstanding achievements, Shalini was recently named one of New Zealand’s YWCA’s Y25: 25 women, 25 years and under, doing incredible things. The YWCA describe these women as some of the most inspirational young women, including some truly exciting, dynamic forces in the start-up scene.

“This is an incredible honour to be recognised amongst some trail blazing young women and also a big acknowledgement to my team at Science Box for their continual support,” said Shalini.

Shalini’s PhD supervisor and Head of the Cancer Single Cell Genomics Laboratory, Dr Bhupinder Pal says, “It is inspiring to see Shalini use her research expertise and love of science to encourage a new generation. We are all incredibly excited for Shalini on receiving this recognition”.

So, where to from here? Shalini says, “apart from completing my PhD and using my research to make a difference for people with breast cancer, I also want to make an impact on STEM education by taking Science Box global!”

Given all that Shalini has achieved already, it is not hard to believe that these goals will indeed become a reality.

Congratulations Shalini, on this well deserved recognition.

Find out more about Science Box https://www.sciencebox.co.nz


Cancer research and charity are all in a day’s work

As a former international student, Pat Thilakasiri – a researcher in the Cancer Therapeutics Development Group at the Olivia Newton-John Cancer Research Institute (ONJCRI) - knows all too well what it’s like to move far away from family and friends to study in a new country.

Many international students leave their usual support networks behind to follow their dream of studying abroad. Many need to undertake part-time or casual work to support themselves while on a student visa.

When news broke of the Coronavirus pandemic, Pat had an inkling that international students would be seriously impacted, so he quickly began to prepare a strategy to support those he thought would be in need.

“With the threat of mass job losses, and without Australian citizenship, I knew early on that many international students would not have money for food, medical or legal assistance, and I knew they would not be eligible for government assistance,” he said.

Pat reached out to his network on Facebook and after a rush of offers to help, on 29 March 2020 he was able to send out his first lot of food packages, containing grocery items that would last for up to two weeks.

“Lockdown meant that many people lost their jobs. There was a group of people that no-one could seem to help – international students. They didn’t have money to pay rent or feed themselves. They were in deep trouble, they were on their own, and we needed to help them,” says Pat.

Pat’s ‘food bag’ initiative for international students has since spread to all the states and territories around Australia (there are groups in each state and territory to coordinate) with some international groups following suit.

So far, Pat estimates they have helped around 3,000 international students across Australia, with the majority located in Victoria and New South Wales. Pat and his supporters are still packing food bags from four distribution centres around Victoria that they have set up.

This isn’t the first time Pat has helped those in need. He coordinated similar projects for people affected by the Boxing Day tsunami in 2004, devastating floods, and for individuals needing housing, or school books.

So, how does he juggle all of this with his full-time job as a scientist at ONJCRI (plus a weekly volunteer job as radio show host on a community radio station)? It’s all about time management, he says. It’s done outside of working hours and he has a lot of people to help him.

“All of us come together. People have donated a lot of food, housing and professional services for these students, including doctors, psychologists and lawyers, who have provided their services free of charge. No money is collected or exchanged – it’s all about providing food and services.”

Pat is working on gastric and breast cancer projects at ONJCRI and, along with his team, is repurposing a drug, Bazedoxifene, and its analogues to treat cancers by targeting the JAK STAT3 pathway (a chain of interactions between proteins in a cell which is involved in processes such as immunity, cell division, cell death and tumour formation).

In addition to this important research, it’s clear that charity is also a huge part of Pat’s life.

“I think as a human you should always help other people. It is our ultimate duty to help whoever is in trouble. In this case, Coronavirus doesn’t distinguish whether you are white, whether you are from Sri Lanka, whether you are rich or poor. It’s simple - when people are in need, people should help each other.”


Early access to new National Drug Discovery Centre

ONJCRI Director, Prof Matthias Ernst has been named as one of two inaugural recipients of subsidised access to the newly opened National Drug Discovery Centre (NDDC) at the Walter and Eliza Hall Institute of Medical Research.  The NDDC has been established to offer researchers in Australia access to state-of-the-art high-throughput screening to fast track the discovery and development of new medicines, so patients can benefit sooner.

The announcement was made on Thursday 12 March by Federal Health Minister the Hon Greg Hunt MP and Victorian Health Minister the Hon Jenny Mikakos MP at the opening of the NDDC.

This significant investment will enable Prof Ernst, and his team, to progress their pivotal work that aims to uncover how to make cancer more visible to the immune system and enhance the effect of anti-tumour immune therapies.

“We will identify lead compounds to inhibit a molecule in immune cells that otherwise suppresses the capacity of a patient’s immune system to kill cancer cells,” he said.

“Once these lead compounds have been identified, they provide a starting point to develop novel drugs and to test their efficacy in treating breast, bowel, pancreatic and other solid tumours”.

The announcement provides an exciting opportunity for Prof Ernst and his team to focus on scientific advances in cancer immunotherapy.

“Ultimately, these findings would serve as a starting point for the development of new anti-cancer drugs that could treat breast, bowel, pancreatic and other solid tumours,” Professor Ernst said.

Congratulations also to A/Prof Anthony Don, from the University of Sydney and Centenary Institute who was announced as the other NDDC recipient. A/Prof Don will, who will lead a project to develop new drugs that reverse systemic insulin resistance that causes type 2 diabetes.


Consumer Advocates

Consumer Advocates

Volunteer Position

We are always keen to partner with members of our community who have a shared interest in seeing changes in how cancer is treated and managed.” Consumer Advocates are people who have been affected by cancer – either they have had cancer themselves and are in disease-free remission, they are receiving treatment for cancer, or they are a family member or friend of someone affected by cancer. And while they will work directly with our researchers they are not expected to have a scientific background.

Our Advocates are highly valued and respected members of the ONJCRI volunteer team. It is a personally rewarding experience that provides a unique opportunity to directly inform our cancer research.

If you would like to know more about being an Advocate, please email consumeradvocate@onjcri.org.au


Activation of a distinct genetic pathway can slow the progress of metastatic breast cancer

Metastasis, the spread of tumour cells to distant sites, is the major cause of death for people impacted by cancer.  With no therapeutic cure available, it is clear that new treatments are needed urgently.

In a study published today in the international journal, Cancer Research a journal of the American Association for Cancer Research, investigators at the Olivia Newton-John Cancer Research Institute (the La Trobe University School of Cancer Medicine) have shown that when the protein bone morphogenetic protein-4 (BMP4) is switched off, breast cancer can become more aggressive. BMP4 is active during fetal development and is maintained during adulthood in some healthy organs, including the breast.

In this study, led by investigators Dr Bedrich Eckhardt (a Susan G Komen Postdoctoral Fellow) and Prof Robin Anderson (Head of the Translational Breast Cancer Program), it was hypothesised that restoring BMP4 activity would block the ability of breast tumours to metastasise.

“At its core, this study has demonstrated that high levels of the BMP4 protein in breast cancer patients is associated with a better outcome, linked to a reduction in metastatic breast cancer,” said Prof Anderson.

'This is an exciting finding as there has been no reduction in the rates of mortality for people with metastatic breast cancer for over 20 years,” said Prof Anderson.

This translational research study revealed that levels of the BMP4 protein are often reduced in late stage breast cancer. But when BMP4 levels were restored in preclinical models of metastatic breast cancer, it could block distant metastasis in multiple organs including the lung and bone.  These findings have been achieved through collaboration with researchers at Peter MacCallum Cancer Centre, Fiona Stanley Hospital (University of Western Australia) and MD Anderson Cancer Center (University of Texas, USA).

“As part of the study, we were able to demonstrate how BMP4 activates cellular pathways to block the ability of tumour cells to metastasise,” Dr Eckhardt explains, “and importantly show that key proteins induced by BMP4 are critical to block metastasis by reducing the number of circulating tumour cells within the blood”.

While the ultimate aim is to bring a new therapy into the clinic through clinical trials, the next phase of research will focus on finding a compound that mimics the anti-metastatic actions of BMP4.   

“A current challenge is that BMP4 protein has an active half-life of only 15 minutes or less in the body after administration, so it is not a practical long-term therapy,” said Prof Anderson.  “We will now focus on finding a more therapeutically viable way of mimicking the action of BMP4 in vivo as a new lead therapy for patients with metastatic breast cancer,” said Prof Anderson.

Review the paper in Cancer Research 

Image description: Immunofluorescent staining reveals activation of the BMP-Smad signaling pathway in metastatic breast cancer cells in response to BMP4 stimulation (left panel, not treated; right panel, BMP4 treated). 

 


Researchers discover a new way that immune cells detect cancers and infections

Cancer immunology experts from the Olivia Newton-John Cancer Research Institute (as the La Trobe University School of Cancer Medicine) have joined forces with the Peter Doherty Institute for Infection and Immunity (Doherty Institute) and CSL Limited to determine the molecular basis for how an important component of the immune system, called gamma-delta T cells, detects infections and cancers.

Published in Science, the research team say this breakthrough of discovering how gamma-delta T cells become activated addresses a question that has baffled scientists for 25 years.

Co-lead author, Dr Andreas Behren, ONJCRI Tumour Immunology Laboratory Head said “these findings represent a key advance in our understanding of how gamma-delta T cells function to protect us from disease.”

“We believe that this breakthrough could ultimately lead to the development of new and improved immunotherapy treatments for millions of people worldwide impacted by cancer and infection,” he said.

The study was conducted by University of Melbourne’s Marc Rigau, PhD student at the Doherty Institute, was co-led by Dr Andreas Behren, a Laboratory Head, Dr Adam Uldrich, a Senior Research Fellow at the Doherty Institute, and Professor Dale Godfrey a laboratory head at the Doherty Institute. Prof Jonathan Cebon, ONJCRI Cancer Immunobiology Program Head was also an author on the paper and part of the original research team for the project at ONJCRI’s predecessor the Ludwig Institute.

“This is an exciting finding for the global scientific community,” said Dr Behren, “because there is great potential that these findings could eventually help to develop new immunotherapy treatments for cancer and infections.”

Dr Uldrich explained that gamma-delta T cells are known to respond to the presence of small molecules, known as phosphoantigens, that are produced by bacteria and cancer cells. “This leads to the activation of these gamma-delta T cells and often eradication of the diseased cells,” Dr Uldrich said.

Professor Godfrey said “Up until now, scientists have struggled to understand the fundamental question of how phosphoantigens are detected by gamma-delta T cells.”

“We found that molecules on the surface of the gamma-delta T cells, called T cell receptors, bind to another molecule called butyrophilin 2A1 that is present on many different cell types throughout the body, including cancer cells,” Professor Godfrey said.

“This research project demonstrates the power of collaboration between academia and industry. Nearly a decade ago, we identified Butyrophilin 2A1 as a potential therapeutic target but its precise biological function remained elusive,” said Dr Con Panousis, Senior Director Molecular Biology, CSL Limited and an author on the paper.

“This discovery makes a significant contribution to our understanding of how gamma-delta T cells work and in doing so, paves the way for translating this research into new immunotherapies for the treatment of serious human disease.”

The ONJCRI team will now focus their efforts on the next phase of the project where they will look for opportunities to apply the findings to particular cancers and other diseases.

This research has been made possible thanks to funding from the Australian Research Council, National Health and Medical Research Council, Cancer Council Victoria, the Victorian Cancer Agency and CSL Limited.

The collaborators have filed patents surrounding their discovery.

Read the paper in Science 

Find out more about the Doherty Institute

Find out more about CSL Limited

Cell image description: Part of a melanoma tumour with expression of butyrophilin 2A1 highlighted in green and cell nuclei in blue.


Prestigious grant funding ensures vital breast cancer research continues

Dr Delphine Merino

Dedicated breast cancer researcher Dr Delphine Merino has been awarded the Susan G. Komen Career Catalyst Research Grant to further her vital research into breast cancer metastases.

Through a partnership between Komen – a USA-based breast cancer funding organisation – and Cancer Australia, the grant cements a joint commitment by the funders to support research that will identify and deliver cures for breast cancer worldwide.

This unique and highly competitive research grant will enable Dr Merino to lead her vital research into breast cancer metastases for the next three years.

As Head of the Tumour Progression and Heterogeneity Laboratory in the Translational Breast Cancer Program at the Olivia Newton-John Cancer Research Institute, Dr Merino and her team aim to identify the most aggressive cells in patient tumours which are responsible for breast cancer progression and mortality.

“The mortality associated with breast cancer is largely due to the spread of breast cancer cells to vital organs in the body,” said Dr Merino.

“There is an urgent need to elucidate the genetic properties of malignant cells responsible for metastatic spread and treatment failure,” she said.

Patients are at the heart of her research. Dr Merino’s research is centred on discoveries that will impact patient survival and personalised medicine.

This grant will enable further research to help characterise the ability of malignant cells to metastasise in different organs and resist current therapies. In identifying which therapy metastatic cells will be susceptible to, outcomes for breast cancer patients can be significantly improved.

“Understanding the genetic properties of cancer cells within a tumour will allow us to implement new therapies to treat patients with recurrent disease,” said Dr Merino.

The study of metastatic breast cancer has been the focus of Dr Merino’s research for a number of years.

“As a dedicated breast cancer researcher, I share with the Susan G. Komen Foundation the ultimate goal of reducing breast cancer deaths by 2026. This prestigious grant will ensure continued momentum in my endeavours toward improving the lives of patients with breast cancer.”

Main image description: Labelling of breast cancer cells


Study reveals that gene knockout can combat obesity

Prof John Mariadason

In what started as a research project into colon cancer, has resulted in a major discovery that could lead to a new treatment for obesity. The study, undertaken at the Olivia Newton-John Cancer Research Institute (ONJCRI) and recently published in Nature Communications, has found that inactivating a gene called HDAC3 specifically in the intestine could protect people from diet-induced obesity.

Obesity, and eating high fat diets increases the risk of developing several types of cancer, including colon cancer. The findings from this study may therefore provide hope for some of the 12.5 million Australian adults who are overweight or obese, while also reducing their cancer risk.

In 2014, Prof John Mariadason, Head of the Gastrointestinal Cancer Program at ONJCRI, began a research study looking at the function of a specific set of proteins called histone deacetylases or HDACs in colon cancer. There are 10 HDAC genes within our bodies, and drugs targeting these proteins are currently used to treat blood cancers.

This pre-clinical study originally aimed to assess if these drugs could also be repurposed for treating colon cancer. As part of this study the researchers inactivated the HDAC3 gene in the intestine and colon of mice to assess its impact on colon cancer development.  During these studies the researchers made the remarkable finding that these mice were protected against obesity.

The normal job of the intestine is to absorb nutrients including lipids or fats, and then move these into the liver.  However, the researchers discovered that when HDAC3 is knocked out, the cells in the intestine start doing an additional job – they break down the lipids within the intestinal cells themselves.  This results in less lipid being available for uptake into the body, and ultimately, over time, in a reduction in weight gain.

On identifying this impact, Prof Mariadason expanded the study with Prof Matthew Watt, Head of Department of Physiology, School of Biomedical Sciences at the University of Melbourne; and Prof Andrew Scott, Head, Tumour Targeting Program ONJCRI, Director, Department Of Molecular Imaging And Therapy, Austin Health. It was found that mice that were fed a high fat diet, which is typical for people with diet-inducted obesity, had a significant reduction in body weight in as little as three months.

‘We have found that there is a new role for the HDAC3 gene in the breakdown of fats,’ said Prof Mariadason.

‘We know that obesity is linked to cancer and if we can block this particular gene then we could protect people from diet-induced obesity and a new obesity treatment could be delivered,’ he said.

The next phase of the obesity treatment study will focus on the delivery of HDAC3 targeting drugs specifically to the intestine, as most drugs are absorbed into the whole body rather than just one specific part.

Prof Mariadason explains, ‘We will now look for opportunities to package the drug differently so it can be delivered directly to the intestine including with the use of nanoparticles.’

The colon cancer study has also continued and findings are expected to be released in the next six months.

 

Publication details:

Dávalos-Salas, M., Montgomery, M.K., Reehorst, C.M. et al. Deletion of intestinal Hdac3 remodels the lipidome of enterocytes and protects mice from diet-induced obesity. Nat Commun 10, 5291 (2019). 

 


New imaging centre to expose the secret life of cancer cells

Researchers at the Olivia Newton-John Cancer Research Institute (ONJCRI) will be able to study cancer tumour cells in greater detail at a state-of-the-art imaging centre thanks to a generous $2m grant by the Australian Cancer Research Foundation (ACRF).

The ACRF Centre for Imaging the Tumour Environment was officially opened on 4 October 2019, and will be used to examine how cancer cells are interacting with other cells around them, in their own micro environment. The insights, provided by imaging machines including Multiphoton and Confocal Microscopes and a NanoString Molecular Barcoding Scanner, will assist the development of new treatments, including new forms of immunotherapy and personalised medicine - relatively new approaches to cancer that are improving survival rates.

ONJCRI researchers will achieve this by studying a variety of tumour samples to investigate how tumour and other cells interact, and better understand which drugs impact specific tumour types. The data from these studies will then be used to identify trends and in turn inform the criteria for targeted treatment options and more personalised cancer treatments.

In the future, these research findings could be provided to clinicians to help inform a patient’s personal treatment plan based on the predicted response of a patient’s unique tumour and cell interactions.

ONJCRI Scientific Director, Prof Matthias Ernst, said the opening of the ACRF Centre for Imaging the Tumour Environment will enable researchers at ONJCRI and the La Trobe Institute of Molecular Science for the first time to observe how cancer cells embed and grow between normal cells.

“The new Centre will literally shine a light on what happens in the immediate environment around a tumour, giving us the information we need to develop effective, targeted anti-cancer therapies,” Prof Ernst said.

“We know that tumour cells coerce and corrupt their environment to their advantage. If we understand the interactions and mechanisms they use to do this, we will better understand how to disrupt these processes that fuel the growth of tumours,” he said.

ACRF CEO, Kerry Strydom said; “We are extremely proud to be part of this next chapter for ONJCRI. At ACRF we believe that to find more effective ways to prevent, detect and treat cancers we must seek to understand it better. This initiative is doing just that. We look forward to the impact of findings from the work being done at this new Centre and the difference this will make in the lives of people diagnosed with cancer.”

Find out more about the ACRF Centre for Imaging the Tumour Environment

Find out more about ACRF


John Brumby retires as ONJCRI’s inaugural Chair - Jenny Macklin to become new Chair

After five years as the inaugural Chair of the Olivia Newton-John Cancer Research Institute (ONJCRI), The Hon John Brumby has announced that he will step down from the role, effective 1 November 2019.

Mr Brumby was instrumental in guiding the direction of the ONJCRI when it commenced in 2015 and has been a strong advocate and representative since this time.  Under his leadership, the research team has grown significantly and the outcomes from these projects are having life-changing impact for people with cancer.  His passion has consistently helped to motivate and drive the work of the ONJCRI team and we acknowledge the impact his leadership has had on the Institute’s success to date, including the more than 230 research collaborations and 140 scientific papers published over the last year.

ONJCRI is thrilled to announce that Ms Jenny Macklin has joined the ONJCRI Board and will take over the role of Chair from 1 November 2019.

Ms Macklin brings passion and enthusiasm to this role, which are sentiments shared among all members of our Board.  She holds a personal desire to drive change for a better community and this was clearly demonstrated during her political career.  Her community focus also aligns well with the ONJCRI mission of creating a future where cancer is a treatable disease while never losing our focus on finding a cure.

As a former economics research analyst, Jenny Macklin understands the complexities of research environments.  This experience is coupled with the delivery of major community impact projects including the implementation of Australia's first national Paid Parental Leave Scheme, the Closing the Gap framework, and the National Disability Insurance Scheme (NDIS).

Ms Macklin retired from politics in early 2019 when she decided to not stand as a candidate for the seat of Jagajaga at the federal election, a position which she held since 1996.  The ONJCRI is also located within this electorate and Ms Macklin has been a passionate supporter and seen the Institute grow firsthand over the past 5 years.

The ONJCRI is sincerely grateful to Mr Brumby for his longstanding support for both the ONJ Wellness Centre and the Research Institute, his commitment and desire to support research breakthroughs that will have direct benefits for people with cancer.  We are very proud that he has been a part of the Institute story so far, and we look forward to continuing to celebrate the success of the Institute through his role as Chancellor of La Trobe University and our shared La Trobe University School of Cancer Medicine.