An emerging but critical technology to the field, RUN DIPG was able to purchase the 10x Genomics Chromium, Xenium and Visium package at the end of 2023. Together, the platform will greatly enhance the resolution of the Dun Lab’s ability to precisely interrogate the biological drivers of DIPG/DMG. Rather than analysing features within an entire tissue sample, they will be able to analyse the components within individual tumour cells, including quantification and localisation, as well as the interactions between tumour cells and other cell types. Being able to map tumour growth patterns and the complex interplay between the tumour and surrounding cells, will provide crucial insight into where and how tumours are progressing. Consequently, the Dun Lab can now investigate new sequential combination therapy approaches that aim to switch treatment before resistance develops (rather than the current ‘use to failure’ paradigm that has not provided long term survival).

This machine helps the Dun Lab understand the safety of experimental DIPG therapies. Where a new drug or treatment approach is tested in research mice, Dr Duchatel and Dun lab researchers analyse the blood of the mice post-treatment. Just like your GP may order you a blood test to understand your health, the haematology analyser will identify whether the experimental therapy has caused unacceptable stress on liver, kidney or other organ systems – critical information required prior to moving to human clinical trials.

In memory of Ms Jemima Gazley (and home to the likeness of many precious friends since), the Wish Lab is a bespoke cell culture facility established at University of Newcastle. ‘Cell Culture’ refers to growing DIPG/DMG cancer cells in a controlled environment, using flasks (think bottle-shaped petri dish) to store, feed and grow cells for study purposes. The Wish Lab is also home to the ‘JEM-BOT’, a cell culture robot used to streamline repetitive handling tasks in a high-throughput manner. Forming the base of all DIPG/DMG experiments carried out by the Dun Lab, the Wish Lab is in constant use at UON.

A key tool of the Dun Lab, the irradiator allows the team to mimic the effects of radiation therapy in the lab environment. Given RT is the only standard-of-care offering for patients diagnosed with DIPG/DMG, this equipment ensures the Dun Lab can study how to improve response to radiation treatment, and its effect in combination with other experimental therapies.

A research laboratory is a complex setting. There’s academic and professional staff, there’s undergraduate and postgraduate students, there’s volunteers, visitors and of course, the boss! With RUN DIPG’s funding, the Dun Lab welcomed a Research Assistant to the team in 2020, a critical extra set of hands to support the multiple projects ongoing within the University of Newcastle team. A research assistant has a scientific background, plus technical training to ensure experimental assays are performed in a scientifically rigorous, safe, and efficient manner.

Ms Mika Persson (finally) joined the Dun Lab in 2020… hailing from Sweeden, and unable to enter Australia throughout the COVID-19 lockdowns, Mika found herself commencing her postgraduate studies in the laboratory of Prof Dun’s mentor at Southern Denmark University. Supported by RUN DIPG, Mika has been paying particular attention to the surface of DIPG tumour cells throughout her tenure as she searches for a novel characteristic that can be targeted using immune-based therapies. As immune therapy has revolutionised the survival of melanoma and some blood cancers, we are hopeful Mika can find a similarly effective target for DIPG/DMG.

Izac Findlay commenced his PhD in 2022, investigating the ‘Pharmaco-Phospho-Proteo-Genomics of Paediatric High-Grade Glioma’ – in lay terms, understanding the interplay between genes, proteins and protein activity in high-risk brain cancer, and finding drugs that will target these intricate features. Izac has diligently prepared an enormous number of DIPG tumour samples for inclusion in his project, the next phase seeing him undertake training in data analysis and integration at the Swiss Federal Institute of Technology Lausanne with thanks to RUN DIPG’s continued support.

French collaborator Dr Clara Savary joined the Dun Lab in 2023 for 12 weeks thanks to the support of RUN DIPG. As a bioinformatician, Dr Savary shared critical knowledge and workflows with the Dun Lab team as they endeavour to interpret the datasets generated through their work. RUN DIPG has provided further support in 2024, with a second visit to University of Newcastle allowing Dr Savary to work more closely with each team member on their specific projects.

After a long search for the qualified candidate, Yuanhao Jiang joined the University of Newcastle team in June as the RUN DIPG Warrior Jack Scholar. A specialist project based in bioinformatics, Yuanhao will investigate the effect of DNA methylation (a chemical modification that occurs within the body) in DIPG, and how this phenomenon impacts the cell signalling pathways that control tumour growth. Assessing a large number of DIPG/DMG samples, Yuanhao will look at whether tumours group in a certain way based on methylation patterns, and whether this grouping aligns with response or resistance to certain therapies. As we know, there are no specified treatment for DIPG (other than palliative radiation therapy) and so we are hopeful the project will shed some light on which tumours need which treatments.

The crux of DIPG/DMG tumours undoubtedly lies in their biology; Prof Matt Dun and the Dun Lab were able to focus on the gene-controlled features of these tumours in 2020 thanks to RUN DIPG’s support.

Building on preliminary data generated by PhD student Izac Findlay, RUN DIPG funded a pilot study alongside Kids’ Cancer Project to understand whether more/better treatment targets can be identified when we consider both the gene and protein characteristics of a tumour. This is a novel approach; standard analysis provided to paediatric cancer patients includes genome analysis, whereas protein analysis is often unfeasible given the larger amount of tumour tissue required and intricate techniques required to perform the assay. However, if it can be shown that the detailed and expensive work of proteomics can find more/effective treatment targets, this will encourage further funding in support of the approach.

Our largest grant funding to-date, 2023 saw us partner with Tour De Cure to provide $1.2M in project support over the coming years. Led by long term Dun Lab member, Dr Evie Jackson, the team at University of Newcastle will investigate how to improve patient response to the most promising anti-DIPG therapies we have – radiation, paxalisib and ONC201. Despite being awarded her PhD in November 2023, Dr Jackson is considered an emerging expert on DIPG cancer cell biology. Her efforts alongside Dun Lab team members 2018-2021 saw paxalisib and ONC201 enter international clinical trial, and we are keen to see what comes of her dedication in the project at hand.

Dr Ryan Duchatel and the Early Career DIPG Researchers of the Dun Lab were supported in their endeavours to participate in, and contribute towards, national and international collaborative projects thanks to RUN DIPG’s funding awarded March 2023. Highlights to-date include Dr Duchatel and Dr Evangeline Jackson’s attendance of the Society of Neuro-Oncology Annual Meeting 2023, held in Vancouver Canada. As well as a second-to-none networking opportunity, Evangeline received the Marit Mary Swenson Award for Pediatric DMG/DIPG for best ‘abstract’ – the short form description of her latest research findings relating to paxalisib and ONC201 (used in the PNOC022 clinical trial).

RUN DIPG are proud to support the work of Dr Jason Cain at the Hudson Institute, Clayton Victoria. Also a member of the DMG-ACT Pre-clinical Working Group (supporting the latest DMG clinical trial), RUN DIPG has awarded Dr Cain a $64,191.70 contribution to support his team identify new therapies for DIPG. Focused on understanding the mechanisms that drive DIPG/DMG development and progression, we are proud to support critical research needed to improve DIPG survival.

Aiming to understand and enhance the effect of two promising anti-DIPG therapies, RUN DIPG are proud to support the work of Professor Javad Nazarian, at the Children’s National Hospital, Washington D.C, with an $80,000 commitment. Oral therapies ONC201 and paxalisib (that will be studied in the international clinical trial ‘Combination Therapy for the Treatment of Diffuse Midline Gliomas’) will be the focus of Dr Nazarian’s work. His team will look to find ways to improve the rate and duration of response to these two drugs (having previously been deemed safe for paediatric patients) by testing unique triple drug therapy approaches. This work is an extension of past collaborative projects between Prof Nazarian and Professor Matt Dun at the University of Newcastle, Hunter Medical Research Institute. Considered a field leader in DIPG/DMG research, we are looking forward to the insights Prof Nazarian and his team’s work will provide, so that more children may receive robust benefit from ONC201 and paxalisib therapies in their fight against diffuse midline glioma.