Looking To The Past To Find Answers For The Future

“I know from personal experience how destructive cancer can be for both patients and their families,” says Elnaz Tavancheh, one of ONJCRI’s talented PhD students and winner of the 2020 Ronnie Goldberg scholarship.

The loss of two grandparents to cancer is what inspired Elnaz to pursue a career in cancer research. Arriving from her native Iran in 2014, her research sees her turning to historical tumour and blood samples to make a difference to those diagnosed with Stage III melanomas.

She is using an archival dataset from Melanoma Research Victoria, at the Victorian Comprehensive Cancer Centre, to identify molecular and immunological markers in melanomas to help improve the prediction of relapses.

“From the dataset I have identified 100 patients whose archival tumour and blood donations are suitable for study. The samples are around 10 years old which means we know each person’s outcome. Without their selfless donations, we couldn’t conduct this research, so I’m very grateful to them,” says Elnaz.

Melanoma is a type of skin cancer that develops in skin cells called melanocytes and usually occurs on the parts of the body that have been overexposed to the sun. Australia has the world’s highest incidence of melanoma.

Elnaz’s research focuses on patients with Stage III melanoma who have received treatment but where the risk of future relapse remains. Currently, oncologists use a variety of measurements like tumour thickness to predict a patient’s risk of relapse, but for many patients this is not very accurate.

“Stage III melanoma has huge potential for successful intervention and treatment in a clinical setting if we can better predict which patients are going to relapse,” says Elnaz, who is completing her PhD under the supervision of Tumour Immunology Laboratory Head Associate Professor Andreas Behren and postdoctoral research fellow Dr Jessica Duarte.

“What we have discovered so far in cancer research is only the tip of the iceberg — I picked this career to make a difference for people with cancer and to contribute to new and better treatments and I feel like I’m achieving that.

“I love what I’m doing. My supervisors have a huge amount of knowledge. They’re supportive, but give me the freedom to think independently, make decisions and push beyond my limits,” she says.


A new way to understand cancer

When a team of international researchers made headlines around the world after determining the entire human genome, the news caught the attention of then Dr Wei Shi.

It was 2003 and Wei had just arrived in Melbourne from his native China to take up a postdoctoral research fellowship at Deakin University’s School of Information Technology.

“This important milestone gave birth to the field of bioinformatics. At the time I was simply fascinated by this achievement and made the decision to switch my career from computer science to become part of this exciting new discipline called bioinformatics,” says Wei.

Bioinformatics combines biology, computer science, mathematics and statistics to develop methods and software tools for understanding complex biological data.

Wei worked for nine years in Professor Gordon Smyth’s Bioinformatics and Cancer Genomics Lab at the Walter and Eliza Hall Institute of Medical Research (WEHI), where he was promoted to Lab Head in 2016.

In April 2020, Wei was recruited to ONJCRI where he established the Institute’s first Bioinformatics and Cancer Genomics Lab. Since coming on board, Wei has made a huge impact on ONJCRI research by contributing his bioinformatics expertise to many research projects in collaboration with most of the labs at ONJCRI. These projects investigate multiple different cancer types such as gastrointestinal cancer, breast cancer and brain cancer.

Wei’s work has been cited in more than 22,000 studies, and he was named on the Web of Science Highly Cited Researcher list in 2018, 2020 and 2021. This award recognises the world’s most influential researchers and illustrates the multidisciplinary relevance of his work.

Wei’s work on developing and improving bioinformatic methodologies benefits research has a large impact far beyond cancer research. The paper he and his colleague Dr Yang Liao published in NAR Genomics and Bioinformatics in 2020 is a case in point. The paper demonstrates that a time-consuming process called ‘Read Trimming’ can be excluded from the RNA-sequencing process without having a negative impact on results.

“Instead of convincing people to do something, I want to convince them not to do something,” explains Wei. “Our work in this 2020 paper shows that if researchers exclude the computationally intensive ‘Read Trimming’ from their sequence analysis process, they can reduce analysis time by 40 per cent yet gain similar results. Our method is faster and easier.”

Wei’s expertise has led to many collaborations here at ONJCRI and with researchers around Australia and the world.

“I’m passionate about bioinformatics research. I’m really excited every day by what we’re doing — developing new methods that will make a difference to basic science and the way that it impacts on clinical care.”


International Collaboration Key To Driving A Change In Biliary Cancer Outcomes

Biliary cancer is a rare but aggressive type of cancer that forms in the tubes that carry digestive fluid — or bile — through the liver. The cancer claims the lives of more than 700 Australians every year, and several thousands in parts of Asia, particularly North East Thailand.

But a three-year NHMRC grant awarded in 2020 and the power of international collaboration are hoping to change these statistics, with a study that is investigating novel immunotherapy treatments and expanding our knowledge of this poorly understood disease.

“Cancers of the biliary tract are often diagnosed very late,” says Professor John Mariadason, study lead and Head of ONJCRI Gastrointestinal Cancers Program and Oncogenic Transcription Laboratory

“These cancers are also relatively rare, making them difficult to study and understand. For patients, this contributes to their poor prognosis and few effective treatment options. We’re hoping to change that with our research.”

The research grant builds on existing collaborative research with scientists from La Trobe University School of Cancer Medicine, Australia; Khon Kaen University, Thailand; and Keio University, Japan.

John and his Lab have been collaborating with the international researchers for the past four years, publishing a breakthrough paper in 2019, identifying specific genetic changes in 25 biliary cancer cell lines that could inform personalised treatment plans.

The team which includes medical oncologist Oliver Klein and translational scientist A/Prof Andreas Behren at the ONJCRI then discovered that some biliary cancer patients respond to immunotherapy. They also found that the biology of biliary tumours could be broken down into two main groups — the first is when the cancer cells still resemble the normal cells, and the second is when the cells have changed their shape quite considerably.

Using this information, the international team are now exploring novel immunotherapies for biliary tract cancer and seeking to understand why only some patients respond to these treatments. They will also conduct hypothesis-driven drug screening to target the two groups of biliary cancers.

“The Thai and Japanese teams see a lot of biliary tract cancer patients as they’ve worked with this cancer for a long time and have developed expertise in this area,” says John.

Because biliary cancer is rare, the team will combine tumour samples from Australia, Japan and Thailand to discover trends that can inform cancer behaviour and response to treatment.


Understanding Gamma Delta T Cell Function in Cancers

Understanding Gamma Delta T Cell Function in Cancers

PhD Project 2021

Supervisor: Dr Lisa Mielke

 

The Mucosal Immunology and Cancer Laboratory focuses on identifying new immune targets that can be explored to develop novel therapeutics to treat bowel cancer. We study heterogeneous populations of T cells, known as intraepithelial lymphocytes (IELs) that are unique to the gastrointestinal tract. Our preliminary studies show that one population of IELs, known as gamma delta T cells, play a protective role in preventing development and progression of bowel cancer. We are working closely with the Tumour Immunology Laboratory that shares an interest in therapeutically exploiting gamma-delta T cell subsets in multiple cancer types. In this project we will collaboratively study a range of surface receptors and cell-cell crosstalk molecules predicted to modify the function of gamma delta T cells and their ability to engage other immune cell subsets and prevent cancer growth and metastasis. We will study the role of these molecules in gamma delta T cell function, in disease models and patient samples. We will use various techniques including flow cytometry, immunofluorescent microscopy and single cell RNA sequencing. We will determine if gamma delta T cell surface receptor expression can be exploited therapeutically to limit bowel cancer progression. Please contact lisa.mielke@onjcri.org.au for more information about this project and entry requirements for study with La Trobe University and the Olivia Newton-John Cancer Research Institute.