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PROJECTS2019-09-10T10:03:16+10:00

Research Project: Understanding DIPG biology

One of the biggest contributors to there being no treatment for DIPG is a lack of understanding of the basic biology of the disease. Recently, genetic information identified all of the changes in the DNA (mutations) in patients diagnosed with DIPG. One particular mutation, occurs in all patients with DIPG, therefore it is the disease causing mutation. This mutation to a protein called ‘Histone H3’, alters the structure of the proteins holding the DNA together. When Histone H3 is altered, the DNA encoding all of our genes is easily damaged. This leads to additional mutations. Furthermore, the altered structure promotes the activity of genes involved in growth and survival of the damaged cell.

Unfortunately, at the current time, there are no drugs effective at targeting the Histone H3 mutation, therefore it is critical that new research identify genes that can be targeted, and we have commenced a focused research effort to discover ways of targeting H3. We have developed sophisticated models of the H3 mutation in the laboratory and are investigating the biology underpinning the mutation to developed targeted treatments for Histone H3 mutations.

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Research Project: Targeted Treatment for DIPG

We have identified that DIPG cells rely on a specific protein pathway called PI3K, for their survival. Mutations and amplifications of this protein pathway occur in almost all DIPG patients, and therefore PI3K is an attractive therapeutic target in the absence of treatments specific for the Histone H3 mutations. However, PI3K inhibitors have been notoriously ineffective due to their inability to cross the brains protective barrier, the blood-brain-barrier. Targeting this pathway with inhibitors is a promising therapeutic option for children with DIPG. This project aims to overcome the limitations of targeting the PI3K pathway by utilising a new drug that is effective at crossing the blood-brain-barrier and is selective for DIPG cells. This drug is currently in clinical trials for Glioblastoma (GBM) and DIPG.

Additionally, Dr Dun’s research is focused on revealing the protein landscape of DIPG patient samples to get an overall understanding of how these cell differ from normal cells and other cancer cells have we have developed effective treatments of. New precision therapies that have revolutionised the treatment of other more common cancers, target proteins that are altered in cancer, but for patients with DIPG knowing which protein to target has limited the clinical utility of well tolerated FDA approved drugs currently available for other diseases. Therefore, we aim to tailor treatments for individual DIPG patients. Every DIPG diagnosis is different, with a different combination of mutations. In this study we aim to performprotein sequencing on DIPG patient biopsies at diagnosis to help select which drugs will work for each individual patient in real time.

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Research Project: Low THC hemp for improved patient outcomes

Peritumoural oedema or brain swelling is a very serious side effect of glioma and underpins many of the neurological symptoms caused by the tumour. Management of this inflammation sees the use of high-dose corticosteroids use such as dexamethasone, which is thought to suppress inflammation and decrease vasogenic oedema through partial restoration of blood–brain barrier. However, significant side effects are associated with its use, including insomnia, mood changes, headache, dizziness, nausea, stomach pain, leading to considerable extra suffering for these patients. Additionally, recent data also shows that high-dose steroids protects gliomas from the genotoxic stress (cell death) caused by radiotherapy and chemotherapy, reducing treatment efficacy and decreasing overall survival.

For the past 18 months, Dr Dun’s laboratory has been investigating the anti-leukaemia properties of medicinal cannabis, revealing remarkable leukaemia specific anti-cancer activity using plant extracts very low in Δ9-tetrahydrocannabinol (THC, concentration <0.40%). Previously, the majority of studies have shown that the anti-cancer properties of cannabis relate to their THC content. However, the THC content of medicinal cannabis has led to its prohibition due to the serious mental health side effects, limiting its clinical utility.

We are currently testing whether low-THC cannabis (lacking harmful THC) is an effective therapy for DIPG. Additionally, we hope to harness the anti-inflammatory properties of medicinal cannabis, to relieve some of the debilitating symptoms associated with brain inflammation in DIPG – helping children to increase their quality of life.

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Together we make all the difference

Dr Matt Dun awarded Federal Investigator Grant

Dr Matt Dun is a University of Newcastle and HMRI biologist leading leukaemia research projects, but has also become driven to use his knowledge and skills to dig deeper into DIPG

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One person, one family, one community at a time, the Hunter Medical Research Institute (HMRI) fights the illnesses affecting lives throughout the world. Our translational research model aligns over 1600 researchers, students and support staff from Hunter New England Health and the University of Newcastle, inspiring new discoveries to deliver a healthier future.

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