Dr Ryan Duchatel

Dr Ryan Duchatel

Postdoctoral Fellow

School of Biomedical Sciences and Pharmacy (Medical Biochemistry)

Targeting the path of most resistance

Dr Ryan Duchatel, a Postdoctoral Fellow with the University’s School of Biomedical Sciences and Pharmacy, is on a mission to identify combination therapies that inhibit a rare but deadly form of childhood brain cancer.

Ryan Duchatel in a lab

In the second half of 2017, Dr Ryan Duchatel was finishing up his PhD in experimental pharmacology with a focus on schizophrenia. Looking around for a new challenge, Ryan took a position beside established researcher Dr Matt Dun and turned his focus to fighting leukemia.

Soon after, the focus of Ryan’s new team turned to diffuse intrinsic pontine glioma (DIPG). A childhood cancer with a median diagnosis age of 6-7, DIPG has a 1% survival rate at two years from discovery, and is uniformly fatal. It manifests as a tumour of the brain stem, ultimately destroying messaging that controls movement, hearing, speech and finally, breathing.

Discovering that current treatment in the form of radiation therapy only offers transient, short acting benefits, Ryan set about developing new targets for chemotherapy based on identifying proteins that control how DIPG cells grow and survive.

Roadblocks to survival pathways

Moving away from the scattergun approach of radiation therapy, Ryan is using proteomics to look for DIPG specific gene mutations and protein pathways to target with novel drug treatments.

“We’ve spent probably 18 months non-stop, doing long hours of research seven days a week, trying to come up with different treatment paradigms”, Ryan explains.

Recent large scale sequencing studies on DIPG donor tumours have identified a genetic mutation called H3K27M, which drives disease initiation. This detection has provided vital clues as to which co-occurring protein pathways may be vulnerable to inhibition. Ryan is working on inhibiting one specific growth and survival protein pathway called Phosphoinositide 3-kinase (PI3K), which is over expressed in more than 80% of DIPG patients.

Perpetually aggressive, DIPG cells eventually adapt to the inhibitors, changing the proteins they use to grow, and bypassing pathways initially blocked by targeted drug therapies.

“Cells are able to make themselves resistant. But we are trying to identify those main drug protein pathways that cells can use and inhibiting all of their different options – essentially putting in roadblocks to their growth. Hopefully that'll one day lead to killing the tumours”.

“We've been able to identify new drug combinations, to synergistically target together. So instead of two plus two equals four, two plus two equals eight. And you can only really do that by utilising this type of protein analysis.”

From the lab to the clinic

Using donor tissue and animal models, Ryan examines the impact of combination therapies not just on the targeted cells, but the entire system.

“There are lots of different drugs that you can use to kill DIPG cells in a Petri dish. But that doesn't necessarily mean that they'll work in a patient. So, animal models work as our pseudo patients.”

To ensure the efficacy of possible treatments, Ryan also cultures cells to directly test the ability of combination therapies to cross the blood brain barrier, a physical barrier in the brain which prevents toxins, but also helpful chemotherapies, from crossing into the brain.

This work on new combinations of therapies is already being translated into clinical practice.

“The data we've got has helped put a PI3K inhibitor called paxalisib into clinical trials for DIPG in the United States. It was first developed for the use in an aggressive adult brain cancer called glioblastoma, but now those trials have seen paxalisib gain a rare disease designation by the FDA to treat patients with DIPG.”

Collaboration and supports

Ryan has been instrumental in assisting Dr Matt Dun in the development of The Cancer Research Signalling Group at HMRI. Initially reliant on donations and support from global experts and local community such as local charity RUN DIPG (www.rundipg.org), and although still in its infancy, the DIPG program is already informing global therapies, sharing lab materials and data with the best fellow DIPG researchers in the world.

A close bond with the brain cancer community and awareness of the demographic he is working to save, means Ryan is more motivated than ever to pinpoint effective therapies.

Ryan credits Stanford University researcher Associate Professor Michelle Monje, who runs one of the largest DIPG research labs in the world, with facilitating their initial lab work through the donation of tissue samples and cell lines.

“Working on DIPG is an amazing collaborative experience,” Ryan explains.

“We get emails all hours of the night from different people all around the world. We share data and samples and compare results.”

“It's good to know via feedback from the international DIPG research community, that the research we're doing is on the right track to make a real difference.”

Ryan Duchatel in a lab

Targeting the path of most resistance

Dr Ryan Duchatel, a Postdoctoral Fellow with the University’s School of Biomedical Sciences and Pharmacy, is on a mission to identify combination therapies that inhibit a rare but deadly form of childhood brain cancer.

Read more

Career Summary

Biography

Dr Ryan John Duchatel is an Early Career Researcher, achieving his PhD in Experimental Pharmacology in November 2018. This work examined the neurobiology, and immune and genetic fingerprints underpinning schizophrenia contributing to the understanding of the development of schizophrenia, through alterations in neurodevelopment during pregnancy.

Dr Duchatel has since transitioned to the Cancer Signalling Research Group (CSRG) of Dr Matthew Dun as a Post-Doctoral Fellow, based at University of Newcastle, Hunter Medical Research Institute. A specialist in DIPG neurosphere in vitro modelling, Dr Duchatel belongs to a team of staff and students investigating the molecular mechanisms underpinning a rare and deadly form of paediatric brain cancer - 'Diffuse Intrinsic Pontine Glioma' or 'DIPG'. The group combines cellular and molecular biology techniques, in vitro and in vivo modelling utilising patient samples, together with high-resolution, quantitative proteomics. He leads the patient derived xenograft, in vivo DIPG modelling of the CSRG, necessary for translation of the group's pre-clinical findings to the clinical trial setting.

Dr Duchatel's current research project, in conjunction with field-leading DIPG research collaborators (Nazarian, Mueller - DIPG Research Centre of Excellence, Switzerland) investigates new and improved treatment strategies to overcome the limitations of current investigative therapies for children with DIPG. Primarily focused on inhibitors of cell growth pathways controlled by 'PI3K' (Phosphoinositide 3-kinase), this has led to the first, high-resolution, quantitative proteomic analysis of DIPG, and identified the compensatory signalling pathways activated in response to PI3K inhibition, which are now under investigation for clinical utility.

Dr Duchatel engages with both the scientific and lay communities to further the reach and relevance of his research. As the Deputy Chair of the Hunter Cancer Research Alliance’s (HCRA), Future Leaders Group, and member of the 2020 HCRA symposium committee and community engagement committee, his position affords him the opportunity to raise awareness and profile of cancer research. He serves on the scientific advisory committee of the Hunter Cancer Biobank, Australia.


Qualifications

  • Doctor of Philosophy, University of Newcastle
  • Bachelor of Biomedical Sciences, University of Newcastle
  • Bachelor of Biomedical Sciences (Hons), University of Newcastle

Keywords

  • Acute Myeloid Leukaemia
  • Brain Cancer
  • Cancer Biology
  • Diffuse Intrinsic Pontine Glioma
  • Molecular Oncology
  • Neurobiology
  • Neuroscience
  • Schizophrenia

Languages

  • English (Mother)

Professional Experience

UON Appointment

Title Organisation / Department
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Publications

For publications that are currently unpublished or in-press, details are shown in italics.


Journal article (8 outputs)

Year Citation Altmetrics Link
2020 Afrin F, Chi M, Eamens AL, Duchatel RJ, Douglas AM, Schneider J, et al., 'Can hemp help? Low-THC cannabis and non-THC cannabinoids for the treatment of cancer', Cancers, 12 (2020) [C1]
DOI 10.3390/cancers12041033
Citations Scopus - 6Web of Science - 8
Co-authors Jennifer Schneider, Matt Dun, Craig Gedye, Andy Eamens
2020 Dun MD, Mannan A, Rigby CJ, Butler S, Toop HD, Beck D, et al., 'Shwachman Bodian Diamond syndrome (SBDS) protein is a direct inhibitor of protein phosphatase 2A (PP2A) activity and overexpressed in acute myeloid leukaemia', Leukemia, 34 3393-3397 (2020) [C1]
DOI 10.1038/s41375-020-0814-0
Co-authors Sam Faulkner, Anoop Enjeti, Hubert Hondermarck, Nikki Verrills, Brett Nixon, Heather Murray, David Skerrett-Byrne, Matt Dun, Geoffry DeiuliIs
2019 Duchatel RJ, Harms LR, Meehan CL, Michie PT, Bigland MJ, Smith DW, et al., 'Reduced cortical somatostatin gene expression in a rat model of maternal immune activation', PSYCHIATRY RESEARCH, 282 (2019) [C1]
DOI 10.1016/j.psychres.2019.112621
Citations Scopus - 3Web of Science - 3
Co-authors Phillip Jobling, Douglas Smith, Pat Michie, Lauren Harms, Paul Tooney, Deborah Hodgson
2019 Duchatel RJ, Shannon Weickert C, Tooney PA, 'White matter neuron biology and neuropathology in schizophrenia', npj Schizophrenia, 5 1-9 (2019) [C1]
DOI 10.1038/s41537-019-0078-8
Citations Scopus - 6Web of Science - 7
Co-authors Paul Tooney
2019 Duchatel RJ, Jackson ER, Alvaro F, Nixon B, Hondermarck H, Dun MD, 'Signal Transduction in Diffuse Intrinsic Pontine Glioma', PROTEOMICS, 19 (2019) [C1]
DOI 10.1002/pmic.201800479
Citations Scopus - 7Web of Science - 6
Co-authors Matt Dun, Brett Nixon, Hubert Hondermarck
2018 Duchatel RJ, Meehan CL, Harms LR, Michie PT, Bigland MJ, Smith DW, et al., 'Increased complement component 4 (C4) gene expression in the cingulate cortex of rats exposed to late gestation immune activation', SCHIZOPHRENIA RESEARCH, 199 442-444 (2018)
DOI 10.1016/j.schres.2018.03.035
Citations Scopus - 11Web of Science - 9
Co-authors Pat Michie, Lauren Harms, Deborah Hodgson, Douglas Smith, Phillip Jobling, Paul Tooney
2018 Duchatel RJ, Meehan CL, Harms LR, Michie PT, Bigland MJ, Smith DW, et al., 'Late gestation immune activation increases IBA1-positive immunoreactivity levels in the corpus callosum of adult rat offspring', Psychiatry Research, 266 175-185 (2018) [C1]

Animal models of maternal immune activation study the effects of infection, an environmental risk factor for schizophrenia, on brain development. Microglia activation and cytokine... [more]

Animal models of maternal immune activation study the effects of infection, an environmental risk factor for schizophrenia, on brain development. Microglia activation and cytokine upregulation may have key roles in schizophrenia neuropathology. We hypothesised that maternal immune activation induces changes in microglia and cytokines in the brains of the adult offspring. Maternal immune activation was induced by injecting polyriboinosinic:polyribocytidylic acid into pregnant rats on gestational day (GD) 10 or GD19, with brain tissue collected from the offspring at adulthood. We observed no change in Iba1, Gfap, IL1-ß and TNF-a mRNA levels in the cingulate cortex (CC) in adult offspring exposed to maternal immune activation. Prenatal exposure to immune activation had a significant main effect on microglial IBA1-positive immunoreactive material (IBA1+IRM) in the corpus callosum; post-hoc analyses identified a significant increase in GD19 offspring, but not GD10. No change in was observed in the CC. In contrast, maternal immune activation had a significant main effect on GFAP+IRM in the CC at GD19 (not GD10); post-hoc analyses only identified a strong trend towards increased GFAP+IRM in the GD19 offspring, with no white matter changes. This suggests late gestation maternal immune activation causes subtle alterations to microglia and astrocytes in the adult offspring.

DOI 10.1016/j.psychres.2018.05.063
Citations Scopus - 5Web of Science - 4
Co-authors Pat Michie, Lauren Harms, Paul Tooney, Rohan Walker, Douglas Smith, Phillip Jobling, Deborah Hodgson
2016 Duchatel RJ, Jobling P, Graham BA, Harms LR, Michie PT, Hodgson DM, Tooney PA, 'Increased white matter neuron density in a rat model of maternal immune activation - Implications for schizophrenia', Progress in Neuro-Psychopharmacology and Biological Psychiatry, 65 118-126 (2016) [C1]

Interstitial neurons are located among white matter tracts of the human and rodent brain. Post-mortem studies have identified increased interstitial white matter neuron (IWMN) den... [more]

Interstitial neurons are located among white matter tracts of the human and rodent brain. Post-mortem studies have identified increased interstitial white matter neuron (IWMN) density in the fibre tracts below the cortex in people with schizophrenia. The current study assesses IWMN pathology in a model of maternal immune activation (MIA); a risk factor for schizophrenia. Experimental MIA was produced by an injection of polyinosinic:polycytidylic acid (PolyI:C) into pregnant rats on gestational day (GD) 10 or GD19. A separate control group received saline injections. The density of neuronal nuclear antigen (NeuN<sup>+</sup>) and somatostatin (SST<sup>+</sup>) IWMNs was determined in the white matter of the corpus callosum in two rostrocaudally adjacent areas in the 12week old offspring of GD10 (n=10) or GD19 polyI:C dams (n=18) compared to controls (n=20). NeuN<sup>+</sup> IWMN density trended to be higher in offspring from dams exposed to polyI:C at GD19, but not GD10. A subpopulation of these NeuN<sup>+</sup> IWMNs was shown to express SST. PolyI:C treatment of dams induced a significant increase in the density of SST<sup>+</sup> IWMNs in the offspring when delivered at both gestational stages with more regionally widespread effects observed at GD19. A positive correlation was observed between NeuN<sup>+</sup> and SST<sup>+</sup> IWMN density in animals exposed to polyI:C at GD19, but not controls. This is the first study to show that MIA increases IWMN density in adult offspring in a similar manner to that seen in the brain in schizophrenia. This suggests the MIA model will be useful in future studies aimed at probing the relationship between IWMNs and schizophrenia.

DOI 10.1016/j.pnpbp.2015.09.006
Citations Scopus - 18Web of Science - 16
Co-authors Lauren Harms, Pat Michie, Phillip Jobling, Deborah Hodgson, Paul Tooney, Brett Graham
Show 5 more journal articles

Conference (10 outputs)

Year Citation Altmetrics Link
2020 Sinclair MR, Jackson ER, Mannan A, Douglas A, Duchatel RJ, Dun MD, 'Preclinical assessment of the safety and efficacy of targeting N-terminal histone tails in combination with emerging therapeutics for the treatment of diffuse midline glioma', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2020)
Co-authors Matt Dun
2020 Mannan A, Germon ZP, Sillar J, Duchatel RJ, Douglas A, McCarthy K, et al., 'Targeting oxidative stress in high-risk pediatric acute lymphoblastic leukemia', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2020)
Co-authors Matt Dun
2020 Afrin F, Chi M, Woldu A, Duchatel R, Douglas AM, Germon Z, et al., 'The use of low-THC cannabis and non-THC cannabinoids in the complementary treatment of acute myeloid leukemia (AML)', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2020)
Co-authors Jennifer Schneider, Matt Dun, Chenchen Jiang
2020 Woldu AS, Afrin F, Jackson ER, Duchatel RJ, Mannan A, Staudt D, et al., 'Investigation of the in vitro antitumor activity of cannabidiol in diffuse midline gliomas', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2020)
Co-authors Matt Dun, Jennifer Schneider
2019 Duchatel R, Jackson E, Patabendige A, Cain J, Tsoli M, Monje M, et al., 'TARGETING PI3K USING THE BLOOD BRAIN BARRIER PENETRABLE INHIBITOR, GDC-0084, FOR THE TREATMENT OF DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)', NEURO-ONCOLOGY, San Francisco, CA (2019)
DOI 10.1093/neuonc/noz036.024
Citations Web of Science - 1
Co-authors Adjanie Patabendige, Matt Dun
2019 Afrin F, Chi M, Woldu A, Duchatel R, Dun MD, 'Anti-Acute Myeloid Leukaemia Properties of Low-THC Cannabis', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2019)
Co-authors Matt Dun
2018 Duchatel R, Jackson E, Verrills N, Cain J, Monje M, Alvaro F, Dun M, 'Investigating ACVR1 and PI3K as Novel Therapeutic Targets in H3.1 K27M+Diffuse Intrinsic Pontine Glioma', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2018)
Co-authors Matt Dun, Nikki Verrills
2018 Staudt D, Duchatel R, Kahl R, Murray H, Scott R, Verrills N, Dun M, 'Development of Novel Model Systems for the Study of Resistance to Targeted Therapies in Acute Myeloid Leukemia', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2018)
Co-authors Matt Dun, Rodney Scott
2018 Germon Z, Sillar J, Murray H, Duchatel R, Al-mazi J, Verrills N, Dun M, 'Intracellular Oxidative Stress Modulates FLT3 Regulatory Proteins Contributing to Oncogenic Signaling in Acute Myeloid Leukemia', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2018)
Co-authors Matt Dun, Nikki Verrills, Heather Murray
2015 Duchatel R, Jobling P, Graham B, Harms L, Michie P, Hodgson D, Tooney P, 'Modelling white matter neuron pathology in schizophrenia using maternal immune activation', JOURNAL OF NEUROCHEMISTRY, Cairns, AUSTRALIA (2015) [E3]
Co-authors Brett Graham, Paul Tooney, Deborah Hodgson, Phillip Jobling, Pat Michie, Lauren Harms
Show 7 more conferences
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Grants and Funding

Summary

Number of grants 9
Total funding $462,522

Click on a grant title below to expand the full details for that specific grant.


20212 grants / $222,522

COMBATT DMG: Combined anti-tumour targeting of diffuse midline glioma$203,522

Funding body: The Cure Starts Now Foundation

Funding body The Cure Starts Now Foundation
Project Team Associate Professor Matt Dun, Dr Jason Cain, Doctor Ryan Duchatel, Jason Cain
Scheme The Cure Starts Now
Role Investigator
Funding Start 2021
Funding Finish 2022
GNo G2000780
Type Of Funding C3212 - International Not for profit
Category 3212
UON Y

Unravelling genomic heterogeneity of diffuse intrinsic pontine glioma$19,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Associate Professor Matt Dun, Doctor Ryan Duchatel
Scheme Research Grant
Role Investigator
Funding Start 2021
Funding Finish 2021
GNo G2100434
Type Of Funding C3120 - Aust Philanthropy
Category 3120
UON Y

20192 grants / $36,000

Moving safe and well-tolerated therapies from the bench to the clinic for the treatment of childhood brain cancer$26,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Associate Professor Matt Dun, Doctor Ryan Duchatel, Doctor Frank Alvaro, Dr Javad Nazarian, Dr Michelle Monje
Scheme Research Grant
Role Investigator
Funding Start 2019
Funding Finish 2020
GNo G1901488
Type Of Funding C3120 - Aust Philanthropy
Category 3120
UON Y

Preclinical research into the potential applications of GDC-0084 in diffuse intrinsic pontine glioma (DIPG)$10,000

Funding body: Kazia Therapeutics Limited

Funding body Kazia Therapeutics Limited
Project Team Associate Professor Matt Dun, Associate Professor David Ziegler, Doctor Heather Murray, Doctor Ryan Duchatel, Doctor Frank Alvaro
Scheme Research Grant
Role Investigator
Funding Start 2019
Funding Finish 2019
GNo G1801161
Type Of Funding C3111 - Aust For profit
Category 3111
UON Y

20185 grants / $204,000

Proteomic architecture of diffuse pontine intrinsic glioma$100,000

Funding body: McDonald Jones Charitable Foundation

Funding body McDonald Jones Charitable Foundation
Project Team Associate Professor Matt Dun, Doctor Frank Alvaro, Doctor Ryan Duchatel, Doctor Heather Murray, Associate Professor David Ziegler
Scheme Postdoctoral fellowship
Role Investigator
Funding Start 2018
Funding Finish 2020
GNo G1801130
Type Of Funding C3120 - Aust Philanthropy
Category 3120
UON Y

Non-invasive detection of DIPG specific DNA and protein using sequential blood collections$57,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Associate Professor Matt Dun, Doctor Muhammad Fairuz Jamaluddin, Doctor Ryan Duchatel, Doctor Frank Alvaro
Scheme Project Grant
Role Investigator
Funding Start 2018
Funding Finish 2020
GNo G1801235
Type Of Funding C3120 - Aust Philanthropy
Category 3120
UON Y

Enhancing the efficacy of new inhibitors targeting the PI3K–AKT–mTOR signalling axis for the treatment of high-grade diffuse intrinsic pontine gliomas (DIPG)$30,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Associate Professor Matt Dun, Doctor Ryan Duchatel, Doctor Adjanie Patabendige
Scheme Project Grant
Role Investigator
Funding Start 2018
Funding Finish 2018
GNo G1801386
Type Of Funding C3120 - Aust Philanthropy
Category 3120
UON Y

Building international collaborations for DIPG research$10,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Ryan Duchatel, Associate Professor Matt Dun
Scheme Jennie Thomas Medical Research Travel Grant
Role Lead
Funding Start 2018
Funding Finish 2018
GNo G1801371
Type Of Funding C3120 - Aust Philanthropy
Category 3120
UON Y

Targeting oncogenic signalling in DIPG using drugs that cross the blood brain barrier.$7,000

Funding body: Australian Communities Foundation

Funding body Australian Communities Foundation
Project Team Associate Professor Matt Dun, Doctor Ryan Duchatel, Ms Terina Vale
Scheme Isabella and Marcus Paediatric Brainstem Tumour Fund
Role Investigator
Funding Start 2018
Funding Finish 2018
GNo G1800977
Type Of Funding C3112 - Aust Not for profit
Category 3112
UON Y
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Research Supervision

Number of supervisions

Completed1
Current1

Current Supervision

Commenced Level of Study Research Title Program Supervisor Type
2020 PhD Molecular Characterisation of Oncogenic Signalling Networks to Develop Treatment Strategies for Diffuse Intrinsic Pontine Glioma PhD (Medical Biochemistry), College of Health, Medicine and Wellbeing, The University of Newcastle Co-Supervisor

Past Supervision

Year Level of Study Research Title Program Supervisor Type
2019 Honours In vitro efficacy of ONC201 in diffuse intrinsic pontine glioma (DIPG) Biochemistry & Cell Biology, Faculty of Health and Medicine, University of Newcastle Co-Supervisor
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Dr Ryan Duchatel

Position

Postdoctoral Fellow
Cancer Signalling Group
School of Biomedical Sciences and Pharmacy
College of Health, Medicine and Wellbeing

Focus area

Medical Biochemistry

Contact Details

Email ryan.duchatel@newcastle.edu.au
Phone (02) 49854489
Mobile (+61) 419268714

Office

Room LS338
Building Life Science
Location Callaghan
University Drive
Callaghan, NSW 2308
Australia
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