Dr Ryan Duchatel

Dr Ryan Duchatel

Postdoctoral Fellow

School of Biomedical Sciences and Pharmacy (Medical Biochemistry)

Career Summary

Biography

Research Focus:My PhD in Experimental Pharmacology (Awarded Nov 2018) was focused in neuroscience, examining the neurobiology, immune and genetic fingerprints underpinning schizophrenia characterised by altered neurodevelopment. In particular, I focused on why people with schizophrenia have more inhibitory neurons in their white matter than the healthy population, and hypothesised that the maternal immune system may contribute to this following sustained bacterial and viral infections. My work contributed to the understanding of the development of schizophrenia, through alterations in neurodevelopment during pregnancy. To uncover the link between maternal infection and schizophrenia during my PhD, I developed sophisticated methods necessary to investigate brain related disorders – including confocal microscopy, immunohistochemical staining of fixed brain sections, animal modelling and developed new methods to quantify microglia and astrocytes within the brain. This research project has provided me with the necessary tools to now commence a career in brain cancer research. 

Under the supervision of Dr Matt Dun, I am now investigating the molecular mechanisms underpinning a rare and deadly form of paediatric brain cancer called Diffuse Intrinsic Pontine Glioma (DIPG). I have completed short trips to the laboratories of Dr Jason Cain (Hudson Institute of Medical Research, VIC) and A/Prof David Ziegler (Children’s Cancer Institute Australia, NSW), to establish the cell culture based methods required for growing DIPG patient derived cell lines in our laboratory and to learn how to engraft these cell lines in mice models. I have now established these models in Dr Duns laboratory, placing us as only the second laboratory in Australia to have the expertise and infrastructure to conduct DIPG patient xenografts. To date, I have tested a number of promising compounds, known to cross the blood brain barrier, in an effort to develop new treatments for children suffering DIPG.

Career Summary:I am an early career researcher. I completed a Bachelor of Biomedical Science with Honours Class 1 in 2013, and was awarded a PhD (Experimental Pharmacology) by publication, on the 3rdNovember 2018 at the University of Newcastle. Currently I am a Research Assistant/ now Post-Doctoral Researcher (July 2017 – Present) in the cancer signalling laboratory of Dr Matt Dun.

Research Esteem:My PhD program has been highly successful, resulting in three first author publications in internationally recognised schizophrenia research journals including Schizophrenia Research, Progress in Neuropsychopharmacology and Biological Psychiatry and Psychiatry Research. Another paper is currently under review in NPJ Schizophrenia. I have also presented my work at several international and domestic research conferences, including winning best rapid fire presentation at the Hunter Cancer Research Symposium 2018 for a presentation titled “Utilising novel inhibitors of PI3K in the treatment of DIPG”, and best Pecha Kucha Presentation at the Australian Society for Medical Research, Hunter Region Satellite Scientific Meeting 2019. 

Funding: In 2018 I have assisted in the generation of $166K in DIPG related research funding. This funding has been primarily philanthropic, including funding from the Isabella and Marcus Paediatric Brainstem Tumour Fund ($7000), 3x project grants from the Hunter Medical Resarch Institute ($59,000), and the McDonald Jones Homes Charitable Foundation ($100,000). 

Awards:I have been awarded numerous prestigious research PhD scholarships for my work in Schizophrenia and Neuroscience including:

-       Ian Scott PhD Scholarship in Mental Health from Australian Rotary Health - $29,000

-       A.M Wood PhD Scholarship from the Schizophrenia Research Institute - $15,000

-       Australian Society for Neuroscience (ANS) Travel Scholarship in 2015 - $300 

-       Deputy Vice Chancellors (Research) Honours Achievement Scholarship, 2015 - $1000

Contribution to the field of research:I have been heavily involved in research governance, including acting as the Student Representative on the Biological Psychiatry Australia Executive Committee (2015-2016), the Faculty of Health Research Higher Degree Committee (2014-2016), Faculty Board (2015-2016). 

Currently I serve as a member of the Hunter Cancer Research Alliance (HCRA) Future Leaders Group, and the HCRA Biobank Scientific Committee. 

Community EngagementAs an Ian Scott PhD Scholar from Australian Rotary Health, I have given several presentations at local Rotary Clubs, outlining my research progress and achievements to date, including the Rotary Clubs of Newcastle and Maitland. This is ongoing.

Supervision and Mentoring:I consider student training and their mentoring to be a very large part of my responsibilities as a Research Assistant/Early Post-Doctoral Researcher. I mentor many honours and research higher degree students in Dr Dun’s laboratory. In addition, I have been heavily involved with undergraduate teaching, including acting as lead demonstrator for professional skills, biochemistry and molecular biology courses to the Bachelor of Biomedical Science programs, Bachelor of Pharmacy and Bachelor of Nutrition and Dietetics programs. 


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)

Fields of Research

Code Description Percentage
110106 Medical Biochemistry: Proteins and Peptides (incl. Medical Proteomics) 20
111201 Cancer Cell Biology 80

Professional Experience

UON Appointment

Title Organisation / Department
Postdoctoral Fellow University of Newcastle
School of Biomedical Sciences and Pharmacy
Australia
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Publications

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


Journal article (6 outputs)

Year Citation Altmetrics Link
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 - 1
Co-authors Paul Tooney
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)

© 2019 Alterations in GABAergic interneurons and glutamic acid decarboxylase (GAD) are observed in the brains of people with schizophrenia. Studies also show increased density of ... [more]

© 2019 Alterations in GABAergic interneurons and glutamic acid decarboxylase (GAD) are observed in the brains of people with schizophrenia. Studies also show increased density of interstitial white matter neurons (IWMN), including those containing GAD and somatostatin (SST) in the brain in schizophrenia. Maternal immune activation can be modelled in rodents to investigate the relationship between prenatal exposure to infections and increased risk of developing schizophrenia. We reported that maternal immune activation induced an increase in density of somatostatin-positive IWMN in the adult rat offspring. Here we hypothesised that maternal immune activation induced in pregnant rats by polyinosinic:polycytidylic acid would alter SST and GAD gene expression as well as increase the density of GAD-positive IWMNs in the adult offspring. SST gene expression was significantly reduced in the cingulate cortex of adult offspring exposed to late gestation maternal immune activation. There was no change in cortical GAD gene expression nor GAD-positive IWMN density in adults rats exposed to maternal immune activation at either early or late gestation. This suggests that our model of maternal immune activation induced by prenatal exposure of rats to polyinosinic:polycytidylic acid during late gestation is able to recapitulate changes in SST but not other GABAergic neuropathologies observed in schizophrenia.

DOI 10.1016/j.psychres.2019.112621
Co-authors Paul Tooney, Pat Michie, Deborah Hodgson, Phillip Jobling, Douglas Smith
2019 Duchatel RJ, Jackson ER, Alvaro F, Nixon B, Hondermarck H, Dun MD, 'Signal Transduction in Diffuse Intrinsic Pontine Glioma.', Proteomics, 19 e1800479 (2019)
DOI 10.1002/pmic.201800479
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 - 3Web of Science - 1
Co-authors Douglas Smith, Paul Tooney, Pat Michie, Lauren Harms, Phillip Jobling, Deborah Hodgson
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]

© 2018 Animal models of maternal immune activation study the effects of infection, an environmental risk factor for schizophrenia, on brain development. Microglia activation and c... [more]

© 2018 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 - 4Web of Science - 2
Co-authors Lauren Harms, Rohan Walker, Pat Michie, Douglas Smith, Phillip Jobling, Deborah Hodgson, Paul Tooney
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]

© 2015. Interstitial neurons are located among white matter tracts of the human and rodent brain. Post-mortem studies have identified increased interstitial white matter neuron (I... [more]

© 2015. 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 - 9Web of Science - 7
Co-authors Deborah Hodgson, Phillip Jobling, Pat Michie, Brett Graham, Lauren Harms, Paul Tooney
Show 3 more journal articles

Conference (3 outputs)

Year Citation Altmetrics Link
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 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 Nikki Verrills, Matt Dun
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 Deborah Hodgson, Lauren Harms, Paul Tooney, Brett Graham, Phillip Jobling, Pat Michie
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Grants and Funding

Summary

Number of grants 7
Total funding $221,000

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


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 Doctor 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 Doctor Matt Dun, Associate Professor David Ziegler, Ms 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 / $185,000

Proteomic architecture of diffuse pontine intrinsic glioma$100,000

Funding body: McDonald Jones Charitable Foundation

Funding body McDonald Jones Charitable Foundation
Project Team Doctor Matt Dun, Doctor Frank Alvaro, Doctor Ryan Duchatel, Ms 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$38,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Matt Dun, Doctor Muhammad Fairuz Jamaluddin, Doctor Ryan Duchatel, Doctor Frank Alvaro
Scheme Project Grant
Role Investigator
Funding Start 2018
Funding Finish 2019
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 Doctor 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, Doctor 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 Doctor 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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Dr Ryan Duchatel

Position

Postdoctoral Fellow
Cancer Signalling Group
School of Biomedical Sciences and Pharmacy
Faculty of Health and Medicine

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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