Associate Professor Matt Dun

Associate Professor Matt Dun
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2020 Project Grant
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2018 Project Grant
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2018 Project Grant
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2018 Project Grant
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2018 Project Grant
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2017 Project Grant
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Travel Grant
2017 Travel Grant
Equipment Grant
2017 Equipment Grant
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2016 Project Grant
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2016 Project Grant
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2016 Project Grant
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2015 Project Grant
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2015 Project Grant
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2015 Project Grant
Travel Grant
2015 Travel Grant
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2014 Project Grant
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2013 Project Grant
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2013 Project Grant
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2012 Project Grant

Biography

Dedication, collaboration, and hard work are the hallmarks of Associate Professor Matt Dun’s medical research career, which employs cutting edge technologies to develop new treatments for children diagnosed with the most aggressive forms of cancer.

Associate Professor Dun is a National Health and Medical Research Council (NHMRC) Investigator, and Chad Tough Defeat DIPG New Investigator, decorated with 27 national and international awards including the NSW Premier’s Outstanding Cancer Research Fellow 2019, a Tall Poppy Science award in 2020 and an International DIPG Big Hero Award in 2022 (presented to him Washington DC). In 2022 alone, he has attracted almost $3 million in research funding and in the past 10 months published in the most prestigious journals including Science Signaling, Neuro-Oncology, Nature Genetics and Cancer Discovery.

This year also marks the early stages of translation of Associate Professor Dun’s extensive pre-clinical efforts into clinical trials. Discoveries from his team the Cancer Signalling Research Group (DunLab) have led to the commencement of an adaptive combination therapy international phase II clinical trial (NCT05009992) for patients diagnosed with diffuse midline glioma (DMG). Through a collaboration with clinical colleagues in the US, all patients in the trial will receive the combination of ONC201 (dopamine receptor antagonist) and paxalisib (PI3K/Akt inhibitor, discovered for DMG in his lab). It is hoped that such strategic combination of therapies will start to increase the numbers of long-term survivors, and thereby provide hope for families diagnosed with the worst of childhood cancers.

 

What are your research interests?

My research program is focused on developing new anti-leukaemia drugs and determining their mechanism of action, synthesised in collaboration with the University of New South Wales. This targeted anti-cancer approach is complemented by a program of discovery research focused on furthering our understandings into how common gene mutations regulate the growth, survival and proliferation of cancer cells.

I am also interested in how normal healthy stem cells stored in the bone marrow grow and develop (cellular signalling) in response to signals or growth factors from the immune system. Hence, I have a research program studying the molecular switches regulated by the activity of protein phosphatases.

Finally, all of the complex and intricate activities of our cells (cellular physiology) are regulated through the actions of proteins, therefore I have a significant interest in methods that help us study the composition and function of proteins. Techniques such as mass spectrometry and biochemical techniques that can help us to understand the function of individual proteins and proteins that form complexes.

 

Why did you get into research?

The ability to make discoveries that one day may improve the health of our community is an honour that not many professions can lay claim to. Also research is about choosing your own adventure and I love that about the job.

 

What would be the ultimate goal for your research?

The end goal is to take one of our basic research discoveries and translate it into an improved health outcome for our community. I am committed to the training of talented local students and mentoring them in their research careers. This increased intellectual property helps to grow our community, providing increased economic and health benefits. 

Specialised/Technical Skills 

  • Characterisation of protein expression
  • Proteomic profiling including iTRAQ and SILAC
  • Phosphoproteomics
  • Quantitative posttranslational modification analysis
  • DNA mutational analysis
  • Cellular imagery
  • Identification of protein-protein interactions via Co-immunoprecipitation
  • Far-Western blotting and Blue Native PAGE
  • Cell culture
  • Functional assays, the generation of recombinant proteins and polyclonal antibodies.

Affiliations

  • PRC for Cancer (PRC-Cancer)
  • Australian Society for Medical Research (ASMR)
  • Australasian Proteomics Society (APS)
  • American Association of Cancer Research (AACR)
  • Haematology Department, The Calvary Mater Hospital
  • Institute of Biochemistry and Molecular Biology, The University of Southern Denmark
  • Chemistry Department, The University of New South Wales
  • Lowy Cancer Research Centre, Prince of Wales Clinical School, Faculty of Medicine, The University of New South Wales
  • Department of Human Genetics, VIB, KU Leuven, Belgium
  • The Alfred Hospital and Monash University
     

2022

Taming free radicals to increase response to standard-of-care treatments for children with high-risk leukaemias
Project Grant
Researchers:

Associate Professor Matt Dun

Description:

Associate Professor Matt Dun from the HMRI Precision Medicine Research Program won for his work in taming free radicals to increase response to standard-of-care treatments for children with high-risk leukaemias that become treatment resistant.

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2020

Targeting NAPDH oxidases enzymes to improve the treatment of high-risk paediatric leukaemias
Project Grant
Researchers:

Dr Matt Dun

2018

Tetraspanin CD9; more than just an exosome marker - A novel biomarker to target for prostate cancer
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Description:

Currently the major hurdle facing the successful treatment of solid cancers is the development of metastases (tumour spread), and our lack of understanding of what controls this process.

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Developing new treatments for resistance in acute myeloid leukaemia
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Researchers:
Description:

Treatment for the most common and deadly form of blood cancer (acute myeloid leukaemia) hasn’t changed in over 40 years. New treatments fail because leukaemia’s genes have a high propensity to mutate, causing rapid resistance to therapies. We have discovered that these gene mutations cause chemical-modifications to the cells defence systems. Unrestrained growth of these cancerous cells results in the production of excess reactive by-products that progressively change the cancer, making long-term treatment response and patient survival unlikely. This project will test whether targeting these chemical-modifications will be a more effective new treatment strategy.

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Targeting DNA repair for the improved treatment of blood cancers
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Researchers:

Dr Matt Dun, Dr Nikki Verrills

Description:

By inhibiting a key player in the DNA repair pathway we could improve the effectiveness of chemotherapeutic treatments.

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Early detection and monitoring of DIPG
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Researchers:
Description:

Half of all malignant childhood gliomas arise in the brainstem, most frequently in the ventral pons as diffuse intrinsic pontine gliomas (DIPG). The anatomical location of the tumour precludes surgical resection, leaving only radiotherapy as the established therapy. Unfortunately, radiotherapy is only temporarily beneficial, and occasionally completely fails, leaving patients without treatment option.

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2017

JAK3 Signalling in T-cell ALL: KU Leuven - VIB, COOLS - UoN-HCRA, DUN collaboration
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Researchers:
Description:

To aid international collaboration with KU Leuven - VIB in Belgium.

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Tetraspanin CD9; more than just an exosome marker - A novel biomarker to target for prostate cancer
Project Grant
Description:

Currently the major hurdle facing the successful treatment of solid cancers is the development of metastases (tumour spread), and our lack of understanding of what controls this process.

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Determining the mechanisms underpinning leukaemic transformation for children suffering from Shwachman-Diamond Syndrome (SDS)
Project Grant
Researchers:

Dr Matt Dun, Dr Nikki Verrills, Dr Jeremy Robertson

Description:

Shwachman-Diamond-Syndrome (SDS) is an inherited disease that affects 1 in every 76,000 children. Dysfunction of the child’s blood and circulatory system occurs in nearly all patients, causing increased rates of infection and decreased capacity to transport oxygen. Unfortunately, the overall survival of a young person with SDS is only 35 years, and this is attributed to sepsis, organ failure and most frequently the development of leukaemia. 

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MRSP Equipment Grant
Equipment Grant
Researchers:
Description:

ChemiDoc MP System - this equipment will help directly facilitate the advanced research needs of >20 different groups of HMRI: Cancer (Dun, Hondermarck,  Verrills, Skelding, Tanwar, Weidenhofer, Scarlet, Bowden, Thorne etc), Brain and Mental Health  (Cairns, Dickson, Dayas, Jobling, Smith, Brichta, Lim etc) Pregnancy and Reproduction (Nixon,  Aitken, De Iuliis, Roman, Bromfield, Pringle) Information Based Medicine (Scott, Milward, Kiejda), VIVA (Hansbro, Starkey) and therefore an estimated >80 HDR students, ECRs and research assistants. 

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Jennie Thomas Medical Research Travel Grant
Travel Grant
Researchers:

 David Skerrett-Byrne, Prof Phil Hansbro, Dr Matt Dun

2016

Targeting DNA repair for the improved treatment of blood cancers
Project Grant
Description:

Acute myeloid leukaemia (AML) is the most common form of acute leukaemia, and it has the lowest 5yr survival rate at a dismal 24%. Recently, improved technologies have enabled researchers to identify a number of mutations that recur in AML.

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Receptor tyrosine kinase mutations in acute myeloid leukaemia promote PP2A and p53 inhibition through the phosphorylation of SBDS
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Description:

AML (acute myeloid leukemia) is a very aggressive form of leukemia. Tumour suppressor proteins are critically important for normal healthy cells to be protected from genetic mutations. However in AML mutations occur in the genes responsible for stem growth and cell differentiation.

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Tetraspanin CD9; more than just an exosome marker - A novel biomarker to target for prostate cancer
Project Grant
Description:

Currently the major hurdle facing the successful treatment of solid cancers is the development of metastases (tumour spread), and our lack of understanding of what controls this process.

more

2015

Jennie Thomas Medical Research Travel Grant
Travel Grant
Researchers:
Description:

Matt will use his Jennie Thomas medical research travel grant to attend the European Molecular Biology Organisation (EMBO) Targeted Proteomics Course to be held at the Centre for Genomic Regulation, Barcelona, Spain where he will learn the theory and methods necessary to implement targeted proteomics workflow on patient samples which he will then pass onto the researchers of HMRI.
 

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JAK3 Signalling in T-cell ALL: KU Leuven - VIB, COOLS - UoN-HCRA, DUN collaboration
Project Grant
Understanding how lung infections in childhood promote the development of chronic lung diseases in later life
Project Grant
Researchers:
Description:

Early-life lung infections, caused by respiratory bacteria and viruses, lead to permanent alterations in lung structure and function that predispose children to the development of chronic lung diseases such as asthma and emphysema in later-life.

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Tetraspanin CD9; more than just an exosome marker - A novel biomarker to target for prostate cancer
Project Grant
Description:

Currently the major hurdle facing the successful treatment of solid cancers is the development of metastases (tumour spread), and our lack of understanding of what controls this process. 

more

2014

Identification of better diagnostic tools and treatment regimens for children with Shwachman-Diamond Syndrome (SDS)
Project Grant
Description:

Shwachman-Diamond Syndrome (SDS) is an inherited condition affecting bone marrow, the pancreas, skeletal system, and other organ systems. 

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Tetraspanin CD9; more than just an exosome marker - A novel biomarker to target for prostate cancer
Project Grant
Description:

Currently the major hurdle facing the successful treatment of solid cancers is the development of metastases (tumour spread), and our lack of understanding of what controls this process.

more

2013

Defining the role of shwachman-bodien diamond syndrome protein (SBDS) in PP2A inhibition in acute myeloid leukaemia (AML)
Project Grant
Description:

A new treatment for acute myeloid leukaemia

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Identifying novel therapeutic targets for the treatment of Acute Myeloid Leukaemia
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Description:

Finding the ‘disease-causing’ mutations and proteins in Acute Myeloid Leukaemia to develop new treatment strategies.

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2012

Proteomics of Cancer - International Travel Grant
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Researchers: