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Dr Matt Dun

Cancer Institute NSW EC Fellow

School of Biomedical Sciences and Pharmacy

Career Summary

Biography

Research Philosophy 

Dedication, collaboration and hard work are the hallmarks of my medical research career focused on providing novel insights into some of the most common and devastating types of cancer; acute myeloid leukaemia (AML), paediatric T cell acute lymphoblastic leukaemia, breast and prostate cancers. 

My PhD program of research was achieved by publication, with distinction, in less than three years and decorated by eleven national and international research awards. During which I was fortunate to be mentored by two of the Universities most respected scientists in Prof. John Aitken and Prof. Brett Nixon. The significant contributions made to my field by PhD resulted in my dissertation being awarded the Annual Vice Chancellors Award for Research High Degree Excellence (2012), and has subsequently laid the foundations for me to achieve my ambitions of developing a successful and internationally competitive research program here at the University of Newcastle and the Hunter Medical Research Institute (HMRI).

My research program in collaboration with Dr Nicole Verrills and Dr Anoop Enjeti is focused on developing new anti-leukaemia drugs synthesised in collaboration with the UNSW Chemistry Department (Prof Morris). This targeted anti-cancer approach is complemented by a program of discovery research focused on furthering our understandings into how common gene mutations regulate growth, survival and proliferation in cancer cells.This work is funding by the Cancer Institute of NSW whom awarded me an esteemed Early Career Research Fellowship 2014-2016 ('Identifying novel therapeutic targets for the treatment of acute myeloid leukaemia (AML)'). I am also interested in cellular signalling regulated by growth factors in stem cells and have a program of research studying the molecular switch from quiescences to activation regulated by protein phosphatases.

I have been very fortunate to receive the support of the HMRI whose public advocacy has helped to develop my research program. Specifically, generous support from the Life Governor of the HMRI Jennie Thomas and Mrs Alyson Gearing has enabled me to study and work in the laboratories of field leading scientists in Belgium and Denmark. Further, the Estate of the Late Mr James Scott Lawrie and the Hunter Ski Club Project Grants has enabled me to continue my work into developing new treatments for AML and other paediatric blood diseases.

I am very fortunate to have extensive national and international collaborators with field leading scientists and haematologists. These opportunities provide my group with access to the world's most sophisticated technologies and relevant patient samples. These technologies are bridging the very large gap that currently exists between cancer genomics and proteomics. Our sophisticated studies are helping to identify new bona fide biomarkers for the development of new-targeted therapies to treat AML, ALL, breast cancers and prostate cancer.

Aside from research, I am committed to scientific advocacy and the promoting of the research achievements of our young local researchers. I am a Director of the Australian Society for Medical Research (ASMR) and locally I have formed the ASMR Newcastle committee, which now hosts 'The ASMR Satellite Scientific Meeting' annually at the HMRI. This meeting showcases the recent research achievements of young Hunter based scientists and clinicians. The meeting also helps to encourage postgraduate and student interactions and fosters collaborations between researchers affiliated within the Faculty of Health and Medicine, the Faculty of Science and Information Technology and the HMRI. If you would like information on this conference please contact Dr Nicole Ryan Nicole.Ryan@newcastle.edu.au

My goal is to continue to attract talented students to join my research program while continuing to generate the required research funding to enable us to translate our important medical discoveries into new treatments options for cancer patients.

If you are interesting in joining my team or supporting my research please contact me at: Matt.Dun@newcastle.edu.au.

Research Expertise

Since the completion of my PhD I have commenced my postdoctoral training within the Faculty of Health and Medicine Priority Research Centre for Cancer Research at the Hunter Medical Research Institute (HMRI), associated with the Hunter Cancer Research Alliance (HCRA) and in collaboration with the Calvary Mater Hospital Medical Oncology Department. My Research Program is focused on elucidating the biochemical mechanisms that underpin novel anti-cancer therapies for improved treatment of acute myeloid leukaemia (AML), paediatric T cell acute lymphoblastic leukaemia (T ALL), breast and prostate cancers. In this context, my technical strengths in many aspects of cell analysis, including: characterisation of protein expression, proteomic profiling including iTRAQ and SILAC, phosphoproteomics, DNA mutational analysis, cellular imagery, identification of protein-protein interactions via Co-immunoprecipitation, Far-Western blotting and Blue Native PAGE, cell culture, functional assays and the generation of recombinant proteins and polyclonal antibodies has been recognised. My ever growing knowledge and skill base has benefited from close association with national and international colleagues. Funding in 2015 enabled me to conduct leukaemia genomics and animal training at the VIB KU Leuven in Belgium, and funding from  2013 and 2014 has enabled me to spend three months working at Institut for Biokemi og Molekylær Biologi at the Syddansk Universitet where I worked with experts in proteomic assays, including phosphoproteomics, membrane proteomics, glycoproteomics, iTRAQ and SILIC. These phosphoproteomics studies utilised Hunter AML patients samples and is allowing us to determine the role oncogenic signalling has on growth and survival of the cancer which will help us identify novel treatment targets and identify the disease causing mutations that are associated with recurrent DNA mutations These complex investigations are aimed at unravelling the pathogenesis of disease, with the resulting data providing us with a better understanding of each condition. Following this sabbatical I was fortunate to present my work on AML at the American Association of Cancer Research in Washington DC.

In 2013 I received the Australian Society for Medical Research Recipient of the NSW Office for Health and Medical Research Postdoctoral Award for Excellence in Medical Research. This award was presented at the ASMR NSW Scientific Meeting. Commencing 2014 my research program is strongly supported thanks to the Cancer Institute of NSW Early Career Research Fellowship. This funding is for three years and aims to 'Identify novel therapeutic targets for the treatment of Acute Myeloid Leukaemia'. These experiences are helping me to establishing a firm foundation for a productive career in cancer cell biology. My ambitions are to attract talented students and integrate my many technical skills on Australian patients samples and to use model systems to further elucidate the mechanisms of disease. Please contact me if you are interesting in joining my team. Matt.Dun@newcastle.edu.au

Teaching Expertise

• 2012 - 2014: Lecturer, HUBS1202 Human Genomics and Biomolecular Analysis. • 2012 - : Head Tutor, HUBS3302 Bioinformatics and Functional Genomics. • • 2011: Lecturer and Head Demonstrator, BIOL2020 Animal Physiology & Development. • 2011: Head Demonstrator, BIOL3020 Reproductive Physiology & Development head demonstrator. • 2011: Demonstrator, BIOL3001 Advanced Laboratory Skills. • 2010: Lecturer and Head Demonstrator, BIOL2020 Animal Physiology & Development. • 2010: Head Demonstrator, BIOL3020 Reproductive Physiology & Development head demonstrator. • 2010: Demonstrator, BIOL3001 Advanced Laboratory Skills. • 2009: Head Demonstrator, BIOL2020 Animal Physiology & Development. • 2009: Head Demonstrator, BIOL3020 Reproductive Physiology & Development head demonstrator. • 2009: Demonstrator, BIOL3001 Advanced Laboratory Skills. I am a lecturer for the Bachelor of Biomedical Science degree specifically, HUBS1202 Human Genomics and Biomolecular Analysis and HUBS3302 Bioinformatics and Functional Genomics. During my PhD I carried a significant teaching load, lecturing 2nd year Physiology for Biotech/Science students and spending almost 500 hours as Laboratory Head Demonstrator. Also during my studies I played Rugby Union for the University of Newcastle and was awarded runner up for Sports Person of the Year, awarded a University Blue and represented NSW in rugby union for five consecutive years. I was also awarded the Representative Player of the Year for the Newcastle and Hunter Rugby Union and in the same year was awarded the NSW Country Rugby Union Championships Player of the Tournament.

Administrative Expertise

Professional memberships:  • 2015 – Director the Australian Society for Medical Research. • 2014 –, Hunter Cancer Research Alliance Flagship Program in Implementation Scientific Committee Member • 2014, Convenor of the Australian Society for Medical Research (ASMR) Satellite Scientific Meeting • 2013 –, Committee Member of the Australian Society for Medical Research (ASMR) • 2012 –, Member of the American Association of Cancer Research (AACR) • 2012 –, Member of the Australian Leukaemia and Lymphoma Group (ALLG) • 2012 –, Member of the Australian Society of Medical Research (ASMR) • 2011 – 2012. Society of Reproductive Biology (SRB) Australian Student Representative to council • 2010 – 2012. Young Investigators of Reproductive Biology Epididymis Council Co-Chair (International Society) • 2010 – 2012. Priority Research Centre Reproductive Biology Meetings Co-Organiser (Reproductive Sciences, Eggs to Embryos and Mothers and Babies Groups) • 2010. University of Newcastle Research Higher Degree Committee, Conference Organising Chair

Collaborations

• Dr Nicole Verrills Medical Biochemistry, The University of Newcastle and HMRI.

• Dr Anoop Enjeti, Clinical Haematologist, The Calvary Mater Hospital.

• Dr Andrew Wei, Clinical Haematologist, The Alfred Hospital and Monash University.

• Prof Jan Cools and Dr Charley De Bock at the Department of Human Genetic VIB KU Leuven Belgium.

• Prof Martin Larsen, Institute of Biochemistry and Molecular Biology, The University of Southern Denmark.

  • • Prof Steve Ackland, Dr Jenntte Sakoff and Dr Jayne Gilbert, Medical Oncology, The Calvary Mater Hospital and HMRI.

• Prof Hubert Hondermarck, Professor of Medical Biochemistry, The University of Newcastle.

• Prof Martin Larsen, Institute of Biochemistry and Molecular Biology, The University of Southern Denmark.

• Prof Jonathan Morris and Hamish Toop, Chemistry Department, University of New South Wales.

• Prof Richard Locke, Dr Anthony Don and Dr Anchit Khanna Lowy Cancer Research Centre, Prince of Wales Clinical School, Faculty of Medicine, The University of New South Wales.

• Prof Jenny Martin, Clinical Pharmacologist, The Calvary Mater Hospital, The University of Newcastle and HMRI.

• Prof Brett Nixon, Reproductive Science Group, The University of Newcastle and HMRI.

• A/Prof Brett Nixon, Reproductive Science Group, The University of Newcastle and HMRI.


Qualifications

  • PhD (Biological Science), University of Newcastle
  • Bachelor of Biotechnology, University of Newcastle
  • Bachelor of Biotechnology (Honours), University of Newcastle

Keywords

  • Cancer
  • Leukaemia
  • Proteomics
  • Biochemistry
  • Nucleic Acids
  • Phosphoproteomics
  • Protein Chemistry
  • Biochemical Assays
  • Chemical Proteomics
  • Anti-Cancer Drug Targeting

Fields of Research

Code Description Percentage
060109 Proteomics and Intermolecular Interactions (excl. Medical Proteomics) 30
110106 Medical Biochemistry: Proteins and Peptides (incl. Medical Proteomics) 30
111201 Cancer Cell Biology 40

Professional Experience

UON Appointment

Title Organisation / Department
Cancer Institute NSW EC Fellow University of Newcastle
School of Biomedical Sciences and Pharmacy
Australia

Academic appointment

Dates Title Organisation / Department
1/12/2013 -  Cancer Instititue NSW Early Career Fellowship Cancer Instititue NSW
School of Biomedical Sciences and Pharmacy, Medical Biochemistry
Australia
1/01/2013 -  Conference Chair - The Australian Society for Medical Research, Satellite Scientific Meeting Convenor The Australian Society for Medical Research
1/10/2011 - 1/12/2013 HMRI Cancer Research Program Chemical Proteomics Postdoctoral Fellow University of Newcastle
HMRI Cancer Research Program
Australia

Membership

Dates Title Organisation / Department
1/01/2013 -  Membership - The Australian Society for Medical Research The Australian Society for Medical Research
Edit

Publications

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


Chapter (2 outputs)

Year Citation Altmetrics Link
2017 Nixon B, Dun MD, Aitken RJ, 'Proteomic Analysis of Human Spermatozoa', Immune Fertility: Impact of Immune Reactions on Human Fertility, Springer Nature, Switzerland 3-22 (2017) [B1]
DOI 10.1007/978-3-319-40788-3_1
Co-authors John Aitken, Brett Nixon
2010 Dun MD, Mitchell LA, Aitken RJ, Nixon B, 'Sperm-zona pellucida interaction: Molecular mechanisms and the potential for contraceptive intervention', Fertility Control, Springer, Berlin 139-178 (2010) [B1]
Citations Scopus - 11
Co-authors Brett Nixon, John Aitken

Journal article (33 outputs)

Year Citation Altmetrics Link
2018 Nixon B, Johnston SD, Skerrett-Byrne DA, Anderson AL, Stanger SJ, Bromfield EG, et al., 'Proteomic profiling of crocodile spermatozoa refutes the tenet that post-testicular maturation is restricted to mammals.', Mol Cell Proteomics, (2018)
DOI 10.1074/mcp.RA118.000904
Co-authors Elizabeth Bromfield, Brett Nixon
2018 Zhou W, De Iuliis GN, Dun MD, Nixon B, 'Characteristics of the epididymal luminal environment responsible for sperm maturation and storage', Frontiers in Endocrinology, 9 (2018) [C1]
DOI 10.3389/fendo.2018.00059
Citations Scopus - 3Web of Science - 2
Co-authors Geoffry DeiuliIs, Brett Nixon
2018 Almazi JG, Pockney P, Gedye C, Smith ND, Hondermarck H, Verrills NM, Dun MD, 'Cell-Free DNA Blood Collection Tubes Are Appropriate for Clinical Proteomics: A Demonstration in Colorectal Cancer.', Proteomics. Clinical applications, 12 e1700121 (2018) [C1]
DOI 10.1002/prca.201700121
Co-authors Nikki Verrills, Hubert Hondermarck, Craig Gedye, Peter Pockney
2018 Wang TE, Li SH, Minabe S, Knapman AL, Dun MD, Maeda KI, et al., 'Mouse quiescin sulfhydryl oxidases exhibit distinct epididymal luminal distribution with Segment-Specific sperm surface associations', BIOLOGY OF REPRODUCTION, (2018)
DOI 10.1093/biolre/ioy125
Co-authors Brett Nixon
2018 Nixon B, De Iuliis G, Hart H, Zhou W, Mathe A, Bernstein I, et al., 'Proteomic profiling of mouse epididymosomes reveals their contributions to post-testicular sperm maturation', Molecular and Cellular Proteomics, (2018)
Co-authors Elizabeth Bromfield, Andrea Mathe, Brett Nixon, Geoffry DeiuliIs, Muhammad Jamaluddin
2018 Zhou W, Sipilä P, De Iuliis G, Dun MD, Nixon B, 'Analysis of Epididymal Protein Synthesis and Secretion', Jove-Journal of Visualized Experiments, 138 (2018) [C1]
DOI 10.3791/58308
Co-authors Geoffry DeiuliIs, Brett Nixon
2018 Brzozowski JS, Bond DR, Jankowski H, Goldie BJ, Burchell R, Naudin C, et al., 'Extracellular vesicles with altered tetraspanin CD9 and CD151 levels confer increased prostate cell motility and invasion', Scientific Reports, 8 1-13 (2018) [C1]
DOI 10.1038/s41598-018-27180-z
Citations Scopus - 1Web of Science - 1
Co-authors C Scarlett, Kathryn Skelding, Danielle Bond, Judith Weidenhofer
2018 Staudt D, Murray H, Alvaro F, Enjeti A, Verrills N, Dun M, 'Targeting Oncogenic Signaling in Mutant FLT3 Acute Myeloid Leukemia: the Path to Least Resistance (2018)
DOI 10.20944/preprints201809.0435.v1
2018 Li X, Dun MD, Faulkner S, Hondermarck H, 'Neuroproteins in Cancer: Assumed Bystanders Become Culprits', PROTEOMICS, 18 (2018) [C1]
DOI 10.1002/pmic.201800049
Citations Scopus - 1
Co-authors Hubert Hondermarck
2018 Walters JLH, De Iuliis GN, Dun MD, Aitken RJ, McLaughlin EA, Nixon B, Bromfield EG, 'Pharmacological inhibition of arachidonate 15-lipoxygenase protects human spermatozoa against oxidative stress.', Biology of reproduction, 98 784-794 (2018) [C1]
DOI 10.1093/biolre/ioy058
Co-authors Elizabeth Bromfield, Geoffry DeiuliIs, John Aitken, Brett Nixon, Eileen Mclaughlin
2018 Jamaluddin MFB, Ko YA, Kumar M, Brown Y, Bajwa P, Nagendra PB, et al., 'Proteomic profiling of human uterine fibroids reveals upregulation of the extracellular matrix protein periostin', Endocrinology, 159 1106-1118 (2018) [C1]

Copyright © 2018 Endocrine Society The central characteristic of uterine fibroids is excessive deposition of extracellular matrix (ECM), which contributes to fibroid growth and bu... [more]

Copyright © 2018 Endocrine Society The central characteristic of uterine fibroids is excessive deposition of extracellular matrix (ECM), which contributes to fibroid growth and bulk-type symptoms. Despite this, very little is known about patterns of ECM protein expression in fibroids and whether these are influenced by the most common genetic anomalies, which relate to MED12. We performed extensive genetic and proteomic analyses of clinically annotated fibroids and adjacent normal myometrium to identify the composition and expression patterns of ECM proteins in MED12 mutation-positive and mutation-negative uterine fibroids. Genetic sequencing of tissue samples revealed MED12 alterations in 39 of 65 fibroids (60%) from 14 patients. Using isobaric tagged-based quantitative mass spectrometry on three selected patients (n = 9 fibroids), we observed a common set of upregulated (.1.5-fold) and downregulated (,0.66-fold) proteins in small, medium, and large fibroid samples of annotated MED12 status. These two sets of upregulated and downregulated proteins were the same in all patients, regardless of variations in fibroid size and MED12 status. We then focused on one of the significant upregulated ECM proteins and confirmed the differential expression of periostin using western blotting and immunohistochemical analysis. Our study defined the proteome of uterine fibroids and identified that increased ECM protein expression, in particular periostin, is a hallmark of uterine fibroids regardless of MED12 mutation status. This study sets the foundation for further investigations to analyze the mechanisms regulating ECM overexpression and the functional role of upregulated ECM proteins in leiomyogenesis.

DOI 10.1210/en.2017-03018
Citations Scopus - 1Web of Science - 1
Co-authors Manishkumar Jhamb, Muhammad Jamaluddin, Rodney Scott, Hubert Hondermarck, Mark Baker, Pradeep Tanwar
2018 Degryse S, de Bock CE, Demeyer S, Govaerts I, Bornschein S, Verbeke D, et al., 'Correction to: Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia (Leukemia, (2018), 32, 3, (788-800), 10.1038/leu.2017.276)', Leukemia, (2018)

© 2018, The Author(s). Following the publication of this article the authors noted that data describing precisely where phosphorylation sites in proteins modulated following JAK1 ... [more]

© 2018, The Author(s). Following the publication of this article the authors noted that data describing precisely where phosphorylation sites in proteins modulated following JAK1 or JAK3 inhibition in mutant T-ALL samples was not clearly annotated. Therefore an additional sheet has been added to Supplementary Table 2.

DOI 10.1038/s41375-018-0241-7
Co-authors Nikki Verrills
2018 Degryse S, De Bock CE, Demeyer S, Govaerts I, Bornschein S, Verbeke D, et al., 'Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia', Leukemia, 32 788-800 (2018) [C1]

© 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. Mutations in the interleukin-7 receptor (IL7R) or the Janus kinase 3 (JAK3) kinase occur frequen... [more]

© 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. Mutations in the interleukin-7 receptor (IL7R) or the Janus kinase 3 (JAK3) kinase occur frequently in T-cell acute lymphoblastic leukemia (T-ALL) and both are able to drive cellular transformation and the development of T-ALL in mouse models. However, the signal transduction pathways downstream of JAK3 mutations remain poorly characterized. Here we describe the phosphoproteome downstream of the JAK3(L857Q)/(M511I) activating mutations in transformed Ba/F3 lymphocyte cells. Signaling pathways regulated by JAK3 mutants were assessed following acute inhibition of JAK1/JAK3 using the JAK kinase inhibitors ruxolitinib or tofacitinib. Comprehensive network interrogation using the phosphoproteomic signatures identified significant changes in pathways regulating cell cycle, translation initiation, mitogen-activated protein kinase and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT signaling, RNA metabolism, as well as epigenetic and apoptotic processes. Key regulatory proteins within pathways that showed altered phosphorylation following JAK inhibition were targeted using selumetinib and trametinib (MEK), buparlisib (PI3K) and ABT-199 (BCL2), and found to be synergistic in combination with JAK kinase inhibitors in primary T-ALL samples harboring JAK3 mutations. These data provide the first detailed molecular characterization of the downstream signaling pathways regulated by JAK3 mutations and provide further understanding into the oncogenic processes regulated by constitutive kinase activation aiding in the development of improved combinatorial treatment regimens.

DOI 10.1038/leu.2017.276
Citations Scopus - 2Web of Science - 1
Co-authors Nikki Verrills
2017 Ong LK, Page S, Briggs GD, Guan L, Dun MD, Verrills NM, et al., 'Peripheral Lipopolysaccharide Challenge Induces Long-Term Changes in Tyrosine Hydroxylase Regulation in the Adrenal Medulla', Journal of Cellular Biochemistry, 118 2096-2107 (2017) [C1]

© 2016 Wiley Periodicals, Inc. Immune activation can alter the activity of adrenal chromaffin cells. The effect of immune activation by lipopolysaccharide (LPS) on the regulation ... [more]

© 2016 Wiley Periodicals, Inc. Immune activation can alter the activity of adrenal chromaffin cells. The effect of immune activation by lipopolysaccharide (LPS) on the regulation of tyrosine hydroxylase (TH) in the adrenal medulla in vivo was determined between 1 day and 6 months after LPS injection. The plasma levels of eleven cytokines were reduced 1 day after LPS injection, whereas the level for interleukin-10 was increased. The levels of all cytokines remained at control levels until 6 months when the levels of interleukin-6 and -4 were increased. One day after LPS injection, there was a decrease in TH-specific activity that may be due to decreased phosphorylation of serine 31 and 40. This decreased phosphorylation of serine 31 and 40 may be due to an increased activation of the protein phosphatase PP2A. One week after LPS injection, there was increased TH protein and increased phosphorylation of serine 40 that this was not accompanied by an increase in TH-specific activity. All TH parameters measured returned to basal levels between 1 month and 3 months. Six months after injection there was an increase in TH protein. This was associated with increased levels of the extracellular regulated kinase isoforms 1 and 2. This work shows that a single inflammatory event has the capacity to generate both short-term and long-term changes in TH regulation in the adrenal medulla of the adult animal. J. Cell. Biochem. 118: 2096¿2107, 2017. © 2016 Wiley Periodicals, Inc.

DOI 10.1002/jcb.25839
Co-authors Peter Dunkley, Nikki Verrills, Phil Dickson, Linkooi Ong
2017 Murray HC, Dun MD, Verrills NM, 'Harnessing the power of proteomics for identification of oncogenic, druggable signalling pathways in cancer', Expert Opinion on Drug Discovery, 12 431-447 (2017) [C1]

© 2017 Informa UK Limited, trading as Taylor & Francis Group. Introduction: Genomic and transcriptomic profiling of tumours has revolutionised our understanding of cancer. H... [more]

© 2017 Informa UK Limited, trading as Taylor & Francis Group. Introduction: Genomic and transcriptomic profiling of tumours has revolutionised our understanding of cancer. However, the majority of tumours possess multiple mutations, and determining which oncogene, or even which pathway, to target is difficult. Proteomics is emerging as a powerful approach to identify the functionally important pathways driving these cancers, and how they can be targeted therapeutically. Areas covered: The authors provide a technical overview of mass spectrometry based approaches for proteomic profiling, and review the current and emerging strategies available for the identification of dysregulated networks, pathways, and drug targets in cancer cells, with a key focus on the ability to profile cancer kinomes. The potential applications of mass spectrometry in the clinic are also highlighted. Expert opinion: The addition of proteomic information to genomic platforms¿¿proteogenomics¿¿is providing unparalleled insight in cancer cell biology. Application of improved mass spectrometry technology and methodology, in particular the ability to analyse post-translational modifications (the PTMome), is providing a more complete picture of the dysregulated networks in cancer, and uncovering novel therapeutic targets. While the application of proteomics to discovery research will continue to rise, improved workflow standardisation and reproducibility is required before mass spectrometry can enter routine clinical use.

DOI 10.1080/17460441.2017.1304377
Citations Scopus - 3Web of Science - 2
Co-authors Nikki Verrills
2017 Bromfield EG, Mihalas BP, Dun MD, Aitken RJ, McLaughlin EA, Walters JLH, Nixon B, 'Inhibition of arachidonate 15-lipoxygenase prevents 4-hydroxynonenal-induced proteindamage in male germ cells', Biology of Reproduction, 96 598-609 (2017) [C1]
DOI 10.1093/biolre/iox005
Citations Scopus - 5Web of Science - 4
Co-authors Eileen Mclaughlin, Brett Nixon, John Aitken, Elizabeth Bromfield
2017 Hutcheon K, McLaughlin EA, Stanger SJ, Bernstein IR, Dun MD, Eamens AL, Nixon B, 'Analysis of the small non-protein-coding RNA profile of mouse spermatozoa reveals specific enrichment of piRNAs within mature spermatozoa', RNA Biology, 14 1776-1790 (2017) [C1]

© 2017 Taylor & Francis Group, LLC. Post-testicular sperm maturation and storage within the epididymis is a key determinant of gamete quality and fertilization competence. H... [more]

© 2017 Taylor & Francis Group, LLC. Post-testicular sperm maturation and storage within the epididymis is a key determinant of gamete quality and fertilization competence. Here we demonstrate that mouse spermatozoa possess a complex small non-protein-coding RNA (sRNA) profile, the composition of which is markedly influenced by their epididymal transit. Thus, although microRNAs (miRNAs) are highly represented in the spermatozoa of the proximal epididymis, this sRNA class is largely diminished in mature spermatozoa of the distal epididymis. Coincident with this, a substantial enrichment in Piwi-interacting RNA (piRNA) abundance in cauda spermatozoa was detected. Further, features of cauda piRNAs, including; predominantly 29¿31 nts in length; preference for uracil at their 5' terminus; no adenine enrichment at piRNA nt 10, and; predominantly mapping to intergenic regions of the mouse genome, indicate that these piRNAs are generated by the PIWIL1-directed primary piRNA production pathway. Accordingly, PIWIL1 was detected via immunoblotting and mass spectrometry in epididymal spermatozoa. These data provide insight into the complexity and dynamic nature of the sRNA profile of spermatozoa and raise the intriguing prospect that piRNAs are generated in situ in maturing spermatozoa. Such information is of particular interest in view of the potential role for paternal sRNAs in influencing conception, embryo development and intergenerational inheritance.

DOI 10.1080/15476286.2017.1356569
Citations Scopus - 2Web of Science - 2
Co-authors Andy Eamens, Eileen Mclaughlin, Brett Nixon
2017 Watt LF, Panicker N, Mannan A, Copeland B, Kahl RGS, Dun MD, et al., 'Functional importance of PP2A regulatory subunit loss in breast cancer', Breast Cancer Research and Treatment, 166 117-131 (2017) [C1]

© 2017, Springer Science+Business Media, LLC. Purpose: Protein phosphatase 2A (PP2A) is a family of serine/threonine phosphatases that regulate multiple cellular signalling pathwa... [more]

© 2017, Springer Science+Business Media, LLC. Purpose: Protein phosphatase 2A (PP2A) is a family of serine/threonine phosphatases that regulate multiple cellular signalling pathways involved in proliferation, survival and apoptosis. PP2A inhibition occurs in many cancers and is considered a tumour suppressor. Deletion/downregulation of PP2A genes has been observed in breast tumours, but the functional role of PP2A subunit loss in breast cancer has not been investigated. Methods: PP2A subunit expression was examined by immunohistochemistry in human breast tumours, and by qPCR and immunoblotting in breast cancer cell lines. PP2A subunits were inhibited by shRNA, and mutant PP2A genes overexpressed, in MCF10A and MCF7 cells, and growth and signalling in standard and three-dimensional cultures were assessed. Results: Expression of PP2A-Aa, PP2A-Ba and PP2A-B'a subunits was significantly lower in primary human breast tumours and lymph node metastases, compared to normal mammary tissue. PP2A-Aa and the regulatory subunits PP2A-Ba, -Bd and -B'¿ were also reduced in breast cancer cell lines compared to normal mammary epithelial cells. Functionally, shRNA-mediated knockdown of PP2A-Ba, -B'a and -B'¿, but not PP2A-Aa, induced hyper-proliferation and large multilobular acini in MCF10A 3D cultures, characterised by activation of ERK. Expression of a breast cancer-associated PP2A-A mutant, PP2A-Aa-E64G, which inhibits binding of regulatory subunits to the PP2A core, induced a similar hyper-proliferative phenotype. Knockdown of PP2A-Ba also induced hyper-proliferation in MCF7 breast cancer cells. Conclusion: These results suggest that loss of specific PP2A regulatory subunits is functionally important in breast tumourigenesis, and support strategies to enhance PP2A activity as a therapeutic approach in breast cancer.

DOI 10.1007/s10549-017-4403-5
Citations Scopus - 4Web of Science - 2
Co-authors Nikki Verrills
2017 Naudin C, Smith B, Bond DR, Dun MD, Scott RJ, Ashman LK, et al., 'Characterization of the early molecular changes in the glomeruli of Cd151 -/- mice highlights induction of mindin and MMP-10.', Scientific Reports, 7 15987-15987 (2017) [C1]
DOI 10.1038/s41598-017-15993-3
Co-authors Rodney Scott, Leonie Ashman, Danielle Bond, Judith Weidenhofer
2017 de Bock CE, Hughes MR, Snyder K, Alley S, Sadeqzadeh E, Dun MD, et al., 'Protein interaction screening identifies SH3RF1 as a new regulator of FAT1 protein levels', FEBS LETTERS, 591 667-678 (2017) [C1]
DOI 10.1002/1873-3468.12569
Citations Scopus - 1Web of Science - 1
Co-authors Hubert Hondermarck, Rick Thorne
2016 Toop HD, Dun MD, Ross BK, Flanagan HM, Verrills NM, Morris JC, 'Development of novel PP2A activators for use in the treatment of acute myeloid leukaemia', Organic and Biomolecular Chemistry, 14 4605-4616 (2016) [C1]

© The Royal Society of Chemistry. AAL(S), the chiral deoxy analog of the FDA approved drug FTY720, has been shown to inhibit proliferation and apoptosis in several cancer cell lin... [more]

© The Royal Society of Chemistry. AAL(S), the chiral deoxy analog of the FDA approved drug FTY720, has been shown to inhibit proliferation and apoptosis in several cancer cell lines. It has been suggested that it does this by activating protein phosphatase 2A (PP2A). Here we report the synthesis of new cytotoxic analogs of AAL(S) and the evaluation of their cytotoxicity in two myeloid cell lines, one of which is sensitive to PP2A activation. We show that these analogs activate PP2A in these cells supporting the suggested mechanism for their cytotoxic properties. Our findings identify key structural motifs required for anti-cancer effects.

DOI 10.1039/c6ob00556j
Citations Scopus - 7Web of Science - 7
Co-authors Nikki Verrills
2016 Smith AM, Dun MD, Lee EM, Harrison C, Kahl R, Flanagan H, et al., 'Activation of protein phosphatase 2A in FLT3+ acute myeloid leukemia cells enhances the cytotoxicity of FLT3 tyrosine kinase inhibitors', Oncotarget, 7 47465-47478 (2016) [C1]

Constitutive activation of the receptor tyrosine kinase Fms-like tyrosine kinase 3 (FLT3), via co-expression of its ligand or by genetic mutation, is common in acute myeloid leuke... [more]

Constitutive activation of the receptor tyrosine kinase Fms-like tyrosine kinase 3 (FLT3), via co-expression of its ligand or by genetic mutation, is common in acute myeloid leukemia (AML). In this study we show that FLT3 activation inhibits the activity of the tumor suppressor, protein phosphatase 2A (PP2A). Using BaF3 cells transduced with wildtype or mutant FLT3, we show that FLT3-induced PP2A inhibition sensitizes cells to the pharmacological PP2A activators, FTY720 and AAL(S). FTY720 and AAL(S) induced cell death and inhibited colony formation of FLT3 activated cells. Furthermore, PP2A activators reduced the phosphorylation of ERK and AKT, downstream targets shared by both FLT3 and PP2A, in FLT3/ITD+BaF3 and MV4-11 cell lines. PP2A activity was lower in primary human bone marrow derived AML blasts compared to normal bone marrow, with blasts from FLT3-ITD patients displaying lower PP2A activity than WT-FLT3 blasts. Reduced PP2A activity was associated with hyperphosphorylation of the PP2A catalytic subunit, and reduced expression of PP2A structural and regulatory subunits. AML patient blasts were also sensitive to cell death induced by FTY720 and AAL(S), but these compounds had minimal effect on normal CD34+ bone marrow derived monocytes. Finally, PP2A activating compounds displayed synergistic effects when used in combination with tyrosine kinase inhibitors in FLT3-ITD+cells. A combination of Sorafenib and FTY720 was also synergistic in the presence of a protective stromal microenvironment. Thus combining a PP2A activating compound and a FLT3 inhibitor may be a novel therapeutic approach for treating AML.

DOI 10.18632/oncotarget.10167
Citations Scopus - 11Web of Science - 8
Co-authors Nikki Verrills, Leonie Ashman, Kathryn Skelding, Anoop Enjeti
2015 Dun MD, Chalkley RJ, Faulkner S, Keene S, Avery-Kiejda KA, Scott RJ, et al., 'Proteotranscriptomic profiling of 231-BR breast cancer cells: Identification of potential biomarkers and therapeutic targets for brain metastasis', Molecular and Cellular Proteomics, 14 2316-2330 (2015) [C1]

© 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Brain metastases are a devastating consequence of cancer and currently there are no specific biomarkers... [more]

© 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Brain metastases are a devastating consequence of cancer and currently there are no specific biomarkers or therapeutic targets for risk prediction, diagnosis, and treatment. Here the proteome of the brain metastatic breast cancer cell line 231-BR has been compared with that of the parental cell line MDA-MB-231, which is also metastatic but has no organ selectivity. Using SILAC and nanoLC-MS/MS, 1957 proteins were identified in reciprocal labeling experiments and 1584 were quantified in the two cell lines. A total of 152 proteins were confidently determined to be up- or down-regulated by more than twofold in 231-BR. Of note, 112/152 proteins were decreased as compared with only 40/152 that were increased, suggesting that down-regulation of specific proteins is an important part of the mechanism underlying the ability of breast cancer cells to metastasize to the brain. When matched against transcriptomic data, 43% of individual protein changes were associated with corresponding changes in mRNA, indicating that the transcript level is a limited predictor of protein level. In addition, differential miRNA analyses showed that most miRNA changes in 231-BR were up- (36/45) as compared with down-regulations (9/45). Pathway analysis revealed that proteome changes were mostly related to cell signaling and cell cycle, metabolism and extracellular matrix remodeling. The major protein changes in 231-BR were confirmed by parallel reaction monitoring mass spectrometry and consisted in increases (by more than fivefold) in the matrix metalloproteinase-1, ephrin-B1, stomatin, myc target-1, and decreases (by more than 10-fold) in transglutaminase-2, the S100 calcium-binding protein A4, and L-plastin. The clinicopathological significance of these major proteomic changes to predict the occurrence of brain metastases, and their potential value as therapeutic targets, warrants further investigation.

DOI 10.1074/mcp.M114.046110
Citations Scopus - 19Web of Science - 18
Co-authors Kelly Kiejda, Rodney Scott, Murray Cairns, Hubert Hondermarck
2015 Faulkner S, Dun MD, Hondermarck H, 'Proteogenomics: Emergence and promise', Cellular and Molecular Life Sciences, 72 953-957 (2015) [C1]

© Springer Basel 2015. Proteogenomics, or the integration of proteomics with genomics and transcriptomics, is emerging as the next step towards a unified understanding of cellular... [more]

© Springer Basel 2015. Proteogenomics, or the integration of proteomics with genomics and transcriptomics, is emerging as the next step towards a unified understanding of cellular functions. Looking globally and simultaneously at gene structure, RNA expression, protein synthesis and posttranslational modifications have become technically feasible and offer a new perspective to molecular processes. Recent publications have highlighted the value of proteogenomics in oncology for defining the molecular signature of human tumors, and translation to other areas of biomedicine and life sciences is anticipated. This minireview will discuss recent developments, challenges and perspectives in proteogenomics.

DOI 10.1007/s00018-015-1837-y
Citations Scopus - 18Web of Science - 19
Co-authors Hubert Hondermarck
2015 Nixon B, Stanger SJ, Mihalas BP, Reilly JN, Anderson AL, Dun MD, et al., 'Next generation sequencing analysis reveals segmental patterns of microRNA expression in mouse epididymal epithelial cells', PLoS ONE, 10 (2015) [C1]

© 2015 Nixon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and repro... [more]

© 2015 Nixon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The functional maturation of mammalian spermatozoa is accomplished as the cells descend through the highly specialized microenvironment of the epididymis. This dynamic environment is, in turn, created by the combined secretory and absorptive activity of the surrounding epithelium and displays an extraordinary level of regionalization. Although the regulatory network responsible for spatial coordination of epididymal function remains unclear, recent evidence has highlighted a novel role for the RNA interference pathway. Indeed, as noncanonical regulators of gene expression, small noncoding RNAs have emerged as key elements of the circuitry involved in regulating epididymal function and hence sperm maturation. Herein we have employed next generation sequencing technology to profile the genome-wide miRNA signatures of mouse epididymal cells and characterize segmental patterns of expression. An impressive profile of some 370 miRNAs were detected in the mouse epididymis, with a subset of these specifically identified within the epithelial cells that line the tubule (218). A majority of the latter miRNAs (75%) were detected at equivalent levels along the entire length of the mouse epididymis. We did however identify a small cohort of miRNAs that displayed highly regionalized patterns of expression, including miR-204-5p and miR-196b-5p, which were down- and up-regulated by approximately 39- and 45-fold between the caput/caudal regions, respectively. In addition we identified 79 miRNAs (representing ~ 21% of all miRNAs) as displaying conserved expression within all regions of the mouse, rat and human epididymal tissue. These included 8/14 members of let-7 family of miRNAs that have been widely implicated in the control of androgen signaling and the repression of cell proliferation and oncogenic pathways. Overall these data provide novel insights into the sophistication of the miRNA network that regulates the function of the male reproductive tract.

DOI 10.1371/journal.pone.0135605
Citations Scopus - 15Web of Science - 14
Co-authors Eileen Mclaughlin, Brett Nixon, Janet Bristow
2014 Goldie BJ, Dun MD, Lin M, Smith ND, Verrills NM, Dayas CV, Cairns MJ, 'Activity-associated miRNA are packaged in Map1b-enriched exosomes released from depolarized neurons.', Nucleic Acids Research, 42 9195-9208 (2014) [C1]
DOI 10.1093/nar/gku594
Citations Scopus - 55Web of Science - 57
Co-authors Nikki Verrills, Murray Cairns, Christopher Dayas
2014 Sadeqzadeh E, De Bock CE, Wojtalewicz N, Holt JE, Smith ND, Dun MD, et al., 'Furin processing dictates ectodomain shedding of human FAT1 cadherin', Experimental Cell Research, 323 41-55 (2014) [C1]

Fat1 is a single pass transmembrane protein and the largest member of the cadherin superfamily. Mouse knockout models and in vitro studies have suggested that Fat1 influences cell... [more]

Fat1 is a single pass transmembrane protein and the largest member of the cadherin superfamily. Mouse knockout models and in vitro studies have suggested that Fat1 influences cell polarity and motility. Fat1 is also an upstream regulator of the Hippo pathway, at least in lower vertebrates, and hence may play a role in growth control. In previous work we have established that FAT1 cadherin is initially cleaved by proprotein convertases to form a noncovalently linked heterodimer prior to expression on the cell surface. Such processing was not a requirement for cell surface expression, since melanoma cells expressed both unprocessed FAT1 and the heterodimer on the cell surface. Here we further establish that the site 1 (S1) cleavage step to promote FAT1 heterodimerisation is catalysed by furin and we identify the cleavage site utilised. For a number of other transmembrane receptors that undergo heterodimerisation the S1 processing step is thought to occur constitutively but the functional significance of heterodimerisation has been controversial. It has also been generally unclear as to the significance of receptor heterodimerisation with respect to subsequent post-translational proteolysis that often occurs in transmembrane proteins. Exploiting the partial deficiency of FAT1 processing in melanoma cells together with furin-deficient LoVo cells, we manipulated furin expression to demonstrate that only the heterodimer form of FAT1 is subject to cleavage and subsequent release of the extracellular domain. This work establishes S1-processing as a clear functional prerequisite for ectodomain shedding of FAT1 with general implications for the shedding of other transmembrane receptors. © 2014.

DOI 10.1016/j.yexcr.2014.02.012
Citations Scopus - 3Web of Science - 3
Co-authors Rick Thorne, Janet Bristow
2014 Hatchwell L, Girkin J, Morten M, Collison A, Mattes J, Foster PS, et al., 'Salmeterol attenuates chemotactic responses in rhinovirus-induced exacerbation of allergic airways disease¿by modulating protein phosphatase 2A', Journal of Allergy and Clinical Immunology, (2014) [C1]

Background: ß-Agonists are used for relief and control of asthma symptoms by reversing bronchoconstriction. They might also have anti-inflammatory properties, but the underpinning... [more]

Background: ß-Agonists are used for relief and control of asthma symptoms by reversing bronchoconstriction. They might also have anti-inflammatory properties, but the underpinning mechanisms remain poorly understood. Recently, a direct interaction between formoterol and protein phosphatase 2A (PP2A) has been described in¿vitro. Objective: We sought to elucidate the molecular mechanisms by which ß-agonists exert anti-inflammatory effects in allergen-driven and rhinovirus 1B-exacerbated allergic airways disease (AAD). Methods: Mice were sensitized and then challenged with house dust mite to induce AAD while receiving treatment with salmeterol, formoterol, or salbutamol. Mice were also infected with rhinovirus 1B to exacerbate lung inflammation and therapeutically administered salmeterol, dexamethasone, or the PP2A-activating drug (S)-2-amino-4-(4-[heptyloxy]phenyl)-2-methylbutan-1-ol (AAL[S]). Results: Systemic or intranasal administration of salmeterol protected against the development of allergen- and rhinovirus-induced airway hyperreactivity and decreased eosinophil recruitment to the lungs as effectively as dexamethasone. Formoterol and salbutamol also showed anti-inflammatory properties. Salmeterol, but not dexamethasone, increased PP2A activity, which reduced CCL11, CCL20, and CXCL2 expression and reduced levels of phosphorylated extracellular signal-regulated kinase 1 and active nuclear factor ¿B subunits in the lungs. The anti-inflammatory effect of salmeterol was blocked by targeting the catalytic subunit of PP2A with small RNA interference. Conversely, increasing PP2A activity with AAL(S) abolished rhinovirus-induced airway hyperreactivity, eosinophil influx, and CCL11, CCL20, and CXCL2 expression. Salmeterol also directly activated immunoprecipitated PP2A in¿vitro isolated from human airway epithelial cells. Conclusions: Salmeterol exerts anti-inflammatory effects by increasing PP2A activity in AAD and rhinovirus-induced lung inflammation, which might potentially account for some of its clinical benefits. © 2013 American Academy of Allergy, Asthma & Immunology.

DOI 10.1016/j.jaci.2013.11.014
Citations Scopus - 20Web of Science - 18
Co-authors Nikki Verrills, Adam Collison, Joerg Mattes, Paul Foster
2013 Smith TB, Dun MD, Smith ND, Curry BJ, Connaughton HS, Aitken RJ, 'The presence of a truncated base excision repair pathway in human spermatozoa that is mediated by OGG1', JOURNAL OF CELL SCIENCE, 126 1488-1497 (2013) [C1]
DOI 10.1242/jcs.121657
Citations Scopus - 55Web of Science - 45
Co-authors Ben Curry, John Aitken
2012 Dun MD, Anderson AL, Bromfield EG, Asquith KL, Emmett BJ, McLaughlin EA, et al., 'Investigation of the expression and functional significance of the novel mouse sperm protein, a disintegrin and metalloprotease with thrombospondin type 1 motifs number 10 (ADAMTS10)', International Journal of Andrology, 35 572-589 (2012) [C1]
DOI 10.1111/j.1365-2605.2011.01235.x
Citations Scopus - 16Web of Science - 13
Co-authors Kelly Asquith, Elizabeth Bromfield, Eileen Mclaughlin, John Aitken, Brett Nixon
2012 Dun MD, Aitken RJ, Nixon B, 'The role of molecular chaperones in spermatogenesis and the post-testicular maturation of mammalian spermatozoa', Human Reproduction Update, 18 420-435 (2012) [C1]
DOI 10.1093/humupd/dms009
Citations Scopus - 34Web of Science - 32
Co-authors John Aitken, Brett Nixon
2011 Redgrove KA, Anderson AL, Dun MD, McLaughlin EA, O'Bryan MK, Aitken RJ, Nixon B, 'Involvement of multimeric protein complexes in mediating the capacitation-dependent binding of human spermatozoa to homologous zonae pellucidae', Developmental Biology, 356 460-474 (2011) [C1]
DOI 10.1016/j.ydbio.2011.05.674
Citations Scopus - 44Web of Science - 44
Co-authors John Aitken, Kate Redgrove, Brett Nixon, Eileen Mclaughlin
2011 Dun MD, Smith ND, Baker MA, Lin M, Aitken RJ, Nixon B, 'The chaperonin containing TCP1 complex (CCT/TRiC) is involved in mediating sperm-oocyte interaction', Journal of Biological Chemistry, 286 36875-36887 (2011) [C1]
DOI 10.1074/jbc.m110.188888
Citations Scopus - 51Web of Science - 44
Co-authors John Aitken, Brett Nixon, Mark Baker
Show 30 more journal articles

Review (1 outputs)

Year Citation Altmetrics Link
2015 Nixon B, Bromfield EG, Dun MD, Redgrove KA, McLaughlin EA, Aitken RJ, 'The role of the molecular chaperone heat shock protein A2 (HSPA2) in regulating human sperm-egg recognition', ASIAN JOURNAL OF ANDROLOGY (2015) [C1]
DOI 10.4103/1008-682X.151395
Citations Scopus - 23Web of Science - 15
Co-authors John Aitken, Brett Nixon, Kate Redgrove, Eileen Mclaughlin, Elizabeth Bromfield

Conference (29 outputs)

Year Citation Altmetrics Link
2017 Rigby C, Toop H, Al Mazi J, Morris J, Enjeti A, Verrills N, Dun M, 'Novel PP2A Inhibitory Protein in C-KIT Mutant Myeloid Progenitor Cells', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2017)
2017 Mannan A, Panicker N, Kahl R, Skelding K, Dun M, Verrills N, 'Reduced Expression of the Protein Phosphatase 2A Regulatory Subunit B55 alpha in Luminal Breast Cancer: Effect on Tumor Progression and Antihormonal Therapy', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2017)
2017 Chen Y, Al Mazi J, Panicker N, Mannan A, Murray H, Dun M, Verrills N, 'To Quantitate DNA Damage Repair Pathways in Human Cancers VIA Establishment of a Sensitive and Quantitative Mass Spectrometry-Based Assay', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2017)
Co-authors Nikki Verrills
2017 Murray H, Kahl R, Smith N, Enjeti A, Larsen M, Verrills N, Dun M, 'Targeting Error-Prone DNA Double-Strand Break Repair in Acute Myeloid Leukaemia (AML)', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2017)
2017 Panicker N, Mannan A, Watt LF, Copeland B, Dun MD, King S, et al., 'Functional role of the tumor suppressor protein phosphatase, PP2A-B55 alpha, in breast cancer', CANCER RESEARCH, Washington, DC (2017)
DOI 10.1158/1538-7445.AM2017-2375
Co-authors Kathryn Skelding, Nikki Verrills
2016 Sillar J, Murray H, Al Mazi J, Skerrett-Byrne D, Kahl R, Flanagan H, et al., 'QUANTITATIVE, HIGH-RESOLUTION PROTEOMICS FOR A SYSTEMS BIOLOGICAL ANALYSIS OF ACUTE MYELOID LEUKEMIA', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2016)
Co-authors Hubert Hondermarck
2016 Al Mazi JT, Verrills N, Smith N, Pockney P, Hondermarck H, Dun M, 'A COMPARISON BETWEEN DATA-DEPENDENT ANALYSIS AND HIGH-RESOLUTION ACCURATE MASS TARGETED PROTEOMICS APPROACHES FOR THE QUANTIFICATION OF PLASMA BIOMARKERS IN COLORECTAL CANCER', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2016)
Co-authors Hubert Hondermarck
2016 Li X, Al Mazi J, Smith N, Dun M, Hondermarck H, 'DEVELOPMENT OF A HIGHLY SENSITIVE AND SPECIFIC TARGETED MASS SPECTROMETRY ASSAY FOR PSA IN PROSTATE CANCER', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2016)
Co-authors Hubert Hondermarck
2016 Mannan A, Panicker N, Kahl R, Dun M, Skelding K, Verrills N, 'REDUCED EXPRESSION OF THE PROTEIN PHOSPHATASE 2A REGULATORY SUBUNIT B55 alpha: IMPACT ON LUMINAL B BREAST CANCER CELLS PROGRESSION AND DNA DAMAGE REPAIR', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2016)
Co-authors Kathryn Skelding
2016 Murray H, Al Mazi J, Kahl R, Flanagan H, Smith N, Enjeti A, et al., 'DNA-PK INHIBITION SENSITIZES FLT3-ITD AML CELLS TO CYTARABINE AND SORAFENIB', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2016)
2016 Chen Y, Al Mazi J, Panicker N, Mannan A, Dun M, Verrills N, 'DEVELOPMENT OF A SENSITIVE AND QUANTITATIVE MASS SPECTROMETRY-BASED ASSAY FOR THE QUANTITATION OF DNA DAMAGE REPAIR PATHWAYS IN HUMAN CANCERS', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2016)
2015 Watt LF, Panicker N, Copeland B, Kahl RGS, Dun MD, Young B, et al., 'PP2A ¿ a novel biomarker and therapeutic target for poor outcome breast cancer', Proceedings of the Lowy Cancer Conference, Sydney (2015) [E3]
Co-authors Kathryn Skelding, Nikki Verrills
2015 Dun M, Murray H, Al-mazi J, Kahl R, Flanagan H, Smith N, et al., 'IDENTIFICATION AND SYNERGISTIC TARGETING OF FLT3-ACTIVATED PATHWAYS IN ACUTE MYELOID LEUKAEMIA', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2015) [E3]
Co-authors Anoop Enjeti, Nikki Verrills
2015 Al-mazi J, Dun M, Smith N, Verrills N, 'DEVELOPMENT OF NOVEL MULTIPLE REACTION MONITORING (MRM) ASSAY FOR BIOMARKER QUANTITATION IN CANCER CELLS', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2015) [E3]
Co-authors Nikki Verrills
2015 Brzozowski J, Coldie B, Jankowski H, Bond D, Scarlett C, Dun M, et al., 'THE EFFECTS OF ALTERED CD9 AND CD151 EXPRESSION ON PROSTATE EXOSOMES', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2015) [E3]
Co-authors Kathryn Skelding, C Scarlett, Danielle Bond, Judith Weidenhofer
2015 Lehman W, Kahl R, Flanagan H, Verrills N, Dun M, 'DETERMINING THE MECHANISM OF LEUKAEMOGENESIS INDUCED BY SHWACHMAN-DIAMOND SYNDROME (SDS) USING COMPARATIVE AND QUANTITATIVE PROTEOMICS', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2015) [E3]
Co-authors Nikki Verrills
2015 Li X, Flanagan H, Kahl R, Rigby C, Verrills N, Dun M, 'CHEMICAL PROTEOMICS TO IDENTIFY THE MECHANISM OF PROTEIN PHOSPHATASE 2A (PP2A) INHIBITION IN ACUTE MYELOID LEUKAEMIA (AML)', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2015) [E3]
Co-authors Nikki Verrills
2015 Mannan A, Panicker N, Watt L, Kahl R, Dun M, Skelding K, Verrills N, 'ROLE OF REDUCED PROTEIN PHOSPHATASE 2A SUBUNIT, B55A, EXPRESSION IN LUMINAL B BREAST CANCER CELL LINE DNA DAMAGE REPAIR PATHWAY', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2015) [E3]
Co-authors Kathryn Skelding, Nikki Verrills
2015 Panicker N, Watt L, Kahl R, Dun M, Greer P, Skelding K, Verrills N, 'REDUCED EXPRESSION OF PROTEIN PHOSPHATASE 2A SUBUNIT, B55A, IN BREAST CANCER DNA DAMAGE REPAIR PATHWAYS', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2015) [E3]
Co-authors Nikki Verrills, Kathryn Skelding, Peter Greer
2015 Rigby C, Kahl R, Flanagan H, Li X, Enjeti A, Verrills N, Dun M, 'CHARACTERISATION OF A NOVEL PP2A INHIBITORY ONCOPROTEIN IN ACUTE MYELOID LEUKAEMIA (AML)', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2015) [E3]
Co-authors Nikki Verrills, Anoop Enjeti
2015 Udeh R, Kahl R, Flanagan H, Verrills N, Dun M, 'IDENTIFYING THE FUNCTIONAL ROLE OF TSR, A NOVEL DRUG TARGET IN AML', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2015) [E3]
Co-authors Nikki Verrills
2014 Dun MD, Chalkley RJ, Keene S, Bradshaw RA, Hondermarck H, 'Proteomics versus Transcriptomics for the Identification of Cancer Biomarkers: the Case of Brain-derived Metastatic Breast Cancer Cells', MOLECULAR & CELLULAR PROTEOMICS (2014) [E3]
Co-authors Hubert Hondermarck
2014 Dun MD, Kahl RGS, Flanagan H, Cairns MMJ, Smith ND, Enjeti AK, et al., 'IDENTIFICATION OF ONCOGENIC SIGNALLING PATHWAYS IN ACUTE MYELOID LEUKAEMIA (AML) PATIENTS BY PHOSPHOPROTEOMICS', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2014) [E3]
Co-authors Murray Cairns, Anoop Enjeti, Nikki Verrills
2014 De Iuliis GN, Verrills NM, Dun MD, 'IN SILICO ANALYSIS OF THE TARGETS OF SMALL-MOLECULE, ANTI-CANCER COMPOUNDS FOR IMPROVED CANCER THERAPEUTICS', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2014) [E3]
Co-authors Geoffry DeiuliIs, Nikki Verrills
2014 Gilbert J, Dun MD, De Iuliis GN, McCluskey A, Sakoff JA, 'SELECTIVELY TARGETING BREAST CANCER CELLS VIA CHECKPOINT ACTIVATION', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2014) [E3]
Co-authors Geoffry DeiuliIs, Adam Mccluskey, Jennette Sakoff
2013 Dun MD, Smith AM, Kahl RGS, Smith ND, Khanna A, Don AS, et al., 'Unraveling the mechanism of action: drugs that activate the tumor suppressor 2A.', CANCER RESEARCH, Washington, DC (2013) [E3]
DOI 10.1158/1538-7445.AM2013-2038
Co-authors Nikki Verrills
2012 Aitken RJ, Nixon B, Redgrove KA, Dun M, Baker MA, 'The molecular origins of defective sperm function', HUMAN REPRODUCTION, Istanbul, TURKEY (2012) [E3]
Co-authors John Aitken, Mark Baker, Kate Redgrove, Brett Nixon
2011 Dun MD, Aitken JR, Nixon B, 'The CCT/TRiC Complex Is Involved in Mediating Sperm-Oocyte Interaction', BIOLOGY OF REPRODUCTION, Portland, OR (2011) [E3]
Co-authors Brett Nixon, John Aitken
2010 Dun MD, Aitken RJ, Nixon B, 'The Chaperonin Containing TCP-1 (CCT/TRIC) Multisubunit Complex is Involved in Mediating Sperm-Oocyte Interactions', Reproduction, Fertility and Development, Sydney (2010) [E3]
Co-authors Brett Nixon, John Aitken
Show 26 more conferences
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Grants and Funding

Summary

Number of grants 33
Total funding $4,628,896

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


20188 grants / $770,657

Elucidating the role of epididymosomes in the transfer of fertility-modulating proteins and regulatory classes of RNA to maturing spermatozoa$539,427

Funding body: NHMRC (National Health & Medical Research Council)

Funding body NHMRC (National Health & Medical Research Council)
Project Team Professor Brett Nixon, Doctor Matt Dun
Scheme Project Grant
Role Investigator
Funding Start 2018
Funding Finish 2020
GNo G1700434
Type Of Funding Aust Competitive - Commonwealth
Category 1CS
UON Y

Investigation of disease markers in asymptomatic patients with colorectal carcinoma or colonic adenomas$81,337

Funding body: Streck

Funding body Streck
Project Team Doctor Matt Dun, Doctor Peter Pockney, Laureate Professor Rodney Scott
Scheme Research Grant
Role Lead
Funding Start 2018
Funding Finish 2019
GNo G1800707
Type Of Funding C3211 - International For profit
Category 3211
UON Y

Capillary Flow Two Dimensional High Pressure Liquid Chromatography (HPLC) system$75,761

Funding body: NHMRC (National Health & Medical Research Council)

Funding body NHMRC (National Health & Medical Research Council)
Project Team Professor Brett Nixon, Doctor Matt Dun, Doctor Nikki Verrills, Professor Hubert Hondermarck, Associate Professor Mark Baker, Doctor Elizabeth Bromfield
Scheme Equipment Grant
Role Investigator
Funding Start 2018
Funding Finish 2018
GNo G1800470
Type Of Funding Scheme excluded from IGS
Category EXCL
UON Y

Targeting Reactive Oxygen Species Generation as a Novel Treatment Target in Acute Myeloid Leukaemia - RA support$25,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Matt Dun, Doctor Jonathan Sillar, Doctor Anoop Enjeti, Doctor Nikki Verrills
Scheme Project Grant
Role Lead
Funding Start 2018
Funding Finish 2018
GNo G1800399
Type Of Funding C3112 - Aust Not for profit
Category 3112
UON Y

Targeting DNA repair for the improved treatment of blood cancers$20,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Matt Dun, Doctor Nikki Verrills
Scheme Project Grant
Role Lead
Funding Start 2018
Funding Finish 2018
GNo G1800611
Type Of Funding C3120 - Aust Philanthropy
Category 3120
UON Y

Novel therapeutic targets and methods for detection of high grade brain cancers$17,991

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Matt Dun
Scheme Project Grant
Role Lead
Funding Start 2018
Funding Finish 2018
GNo G1800874
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, Mr Ryan Duchatel, Ms Terina Vale
Scheme Isabella and Marcus Paediatric Brainstem Tumour Fund
Role Lead
Funding Start 2018
Funding Finish 2018
GNo G1800977
Type Of Funding C3112 - Aust Not for profit
Category 3112
UON Y

Jennie Thomas Medical Research Travel Grant - Nikita Panicker$4,141

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Miss Nikita Panicker, Doctor Nikki Verrills, Doctor Severine Roselli, Doctor Matt Dun
Scheme Jennie Thomas Medical Research Travel Grant
Role Investigator
Funding Start 2018
Funding Finish 2018
GNo G1800024
Type Of Funding C3120 - Aust Philanthropy
Category 3120
UON Y

20179 grants / $1,305,481

Anticancer Properties of Low THC Hemp and its components$600,000

Funding body: Cancer Institute NSW

Funding body Cancer Institute NSW
Project Team Doctor Mengna Chi, Doctor Matt Dun, Associate Professor Jenny Schneider
Scheme Early Career Fellowship
Role Investigator
Funding Start 2017
Funding Finish 2024
GNo G1700667
Type Of Funding C2210 - Aust StateTerritoryLocal - Own Purpose
Category 2210
UON Y

Anticancer properties of cannabis oil and its individual components$400,000

Funding body: Australian Natural Therapeutics Group Pty Ltd

Funding body Australian Natural Therapeutics Group Pty Ltd
Project Team Doctor Matt Dun
Scheme Research Grant
Role Lead
Funding Start 2017
Funding Finish 2018
GNo G1700581
Type Of Funding C3111 - Aust For profit
Category 3111
UON Y

Targeting activated signalling and oxidative stress pathways in acute myeloid leukaemia$150,000

Funding body: Cancer Institute NSW

Funding body Cancer Institute NSW
Project Team Doctor Matt Dun
Scheme Early Career Fellowship
Role Lead
Funding Start 2017
Funding Finish 2019
GNo G1600806
Type Of Funding C2210 - Aust StateTerritoryLocal - Own Purpose
Category 2210
UON Y

HMRI MRSP Special Infrastructure Scheme Chemidoc$56,600

Funding body: HMRI

Funding body HMRI
Project Team

Matt Dun, Hubert Hondermarck, Murray Cairns, Brett Nixon, Phillip Dickson, Nikki Verrills

Scheme HMRI
Role Lead
Funding Start 2017
Funding Finish 2018
GNo
Type Of Funding Aust Competitive - Non Commonwealth
Category 1NS
UON N

Receptor tyrosine kinase mutations in acute myeloid leukaemia promote PP2A and p53 inhibition through the phosphorylation of SBDS$27,500

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Matt Dun, Doctor Nikki Verrills
Scheme Project Grant
Role Lead
Funding Start 2017
Funding Finish 2017
GNo G1700272
Type Of Funding C3120 - Aust Philanthropy
Category 3120
UON Y

Determining the mechanisms underpinning leukaemic transformation for children suffering from Shwachman-Diamond Syndrome (SDS)$25,000

Funding body: Hunter District Hunting Club Inc

Funding body Hunter District Hunting Club Inc
Project Team Doctor Matt Dun, Doctor Nikki Verrills, Doctor Bryony Ross, Doctor Anoop Enjeti, Dr Jeremy Robertson
Scheme Research Funding
Role Lead
Funding Start 2017
Funding Finish 2017
GNo G1701574
Type Of Funding C3120 - Aust Philanthropy
Category 3120
UON Y

Targeting a tumour suppressor for new cancer therapies $24,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Nikki Verrills, Doctor Matt Dun, Doctor Severine Roselli
Scheme Project Grant
Role Investigator
Funding Start 2017
Funding Finish 2018
GNo G1700588
Type Of Funding C3120 - Aust Philanthropy
Category 3120
UON Y

Developing new treatments for resistance in acute myeloid leukaemia$19,000

Funding body: Zebra Equities

Funding body Zebra Equities
Project Team Doctor Matt Dun
Scheme Research Funding
Role Lead
Funding Start 2017
Funding Finish 2017
GNo G1701507
Type Of Funding C3120 - Aust Philanthropy
Category 3120
UON Y

Jennie Thomas Medical Research Travel Grant$3,381

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Mr David Skerrett-Byrne, Professor Phil Hansbro, Doctor Matt Dun
Scheme Jennie Thomas Medical Research Travel Grant
Role Investigator
Funding Start 2017
Funding Finish 2017
GNo G1701070
Type Of Funding C3120 - Aust Philanthropy
Category 3120
UON Y

20161 grants / $100,000

Targeting DNA repair for the improved treatment of blood cancers$100,000

Funding body: Jurox

Funding body Jurox
Project Team Doctor Matt Dun, Doctor Nikki Verrills
Scheme Research Funding
Role Lead
Funding Start 2016
Funding Finish 2016
GNo G1601127
Type Of Funding C3120 - Aust Philanthropy
Category 3120
UON Y

20155 grants / $1,031,250

High resolution fourier transform mass spectrometry platform for the discovery of novel cancer biomarkers and drug targets using label-free and isobaric-tagged approaches for quantitative proteomics$500,000

Funding body: Cancer Instititue NSW

Funding body Cancer Instititue NSW
Project Team

X. Dong Zhang, M.D. Dun, J. Martin, H. Hondermarck, R.J. Aitken, N.M. Verrills, P. Tanwar, R. Scott, M. Kavallaris (UNSW), D. Saunders (USyd)

Scheme Research Equipment Grant
Role Lead
Funding Start 2015
Funding Finish 2016
GNo
Type Of Funding Aust Competitive - Non Commonwealth
Category 1NS
UON N

Advanced Technical Support for Oncology Single Cell Analysis Technologies$300,000

Funding body: Cancer Institute NSW

Funding body Cancer Institute NSW
Project Team Laureate Professor Rodney Scott, Professor Xu Dong Zhang, Professor Hubert Hondermarck, Conjoint Professor Stephen Ackland, Doctor Craig Gedye, Associate Professor Pradeep Tanwar, Doctor Chen Chen Jiang, Doctor Matt Dun, Professor Paul de Souza, Associate Professor Kevin Spring, Dr Tao Liu
Scheme Research Infrastructure Grants
Role Investigator
Funding Start 2015
Funding Finish 2018
GNo G1500824
Type Of Funding C2210 - Aust StateTerritoryLocal - Own Purpose
Category 2210
UON Y

High resolution fourier transform mass spectrometry platform for the discovery of novel cancer biomarkers and drug targets using label-free and isobaric-tagged approaches for quantitative proteomics.$196,250

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Professor Xu Dong Zhang, Doctor Matt Dun, Professor Jennifer Martin, Professor Hubert Hondermarck, Laureate Professor John Aitken, Doctor Nikki Verrills, Associate Professor Pradeep Tanwar, Laureate Professor Rodney Scott, Professor Maria Kavallaris, Dr Darren Saunders
Scheme Equipment Grant
Role Investigator
Funding Start 2015
Funding Finish 2015
GNo G1500935
Type Of Funding Internal
Category INTE
UON Y

Identification of better diagnostic tools and new treatment options for children suffering from Shwachman-Diamond Syndrome (SDS)$25,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Matt Dun, Doctor Nikki Verrills
Scheme Research Grant
Role Lead
Funding Start 2015
Funding Finish 2015
GNo G1500757
Type Of Funding Grant - Aust Non Government
Category 3AFG
UON Y

Jennie Thomas Medical Research Travel Grant$10,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Matt Dun
Scheme Jennie Thomas Medical Research Travel Grant
Role Lead
Funding Start 2015
Funding Finish 2015
GNo G1501429
Type Of Funding C3120 - Aust Philanthropy
Category 3120
UON Y

20146 grants / $1,289,412

Identifying novel therapeutic targets for the treatment of Acute Myeloid Leukaemia$600,000

Funding body: Cancer Institute NSW

Funding body Cancer Institute NSW
Project Team Doctor Matt Dun, Doctor Nikki Verrills, Associate Professor Martin Larsen
Scheme Early Career Fellowship
Role Lead
Funding Start 2014
Funding Finish 2016
GNo G1300952
Type Of Funding Other Public Sector - State
Category 2OPS
UON Y

Tetraspanin CD9; more than just an exosome marker - A novel biomarker to target for prostate cancer$400,000

Funding body: Construction, Forestry, Mining and Energy Union

Funding body Construction, Forestry, Mining and Energy Union
Project Team Doctor Jude Weidenhofer, Doctor Kathryn Skelding, Doctor Matt Dun, Ms Belinda Goldie, Doctor Danielle Bond
Scheme Research Funding
Role Investigator
Funding Start 2014
Funding Finish 2017
GNo G1400921
Type Of Funding C3120 - Aust Philanthropy
Category 3120
UON Y

Visualisation of microparticles for development of biomarkers and targeted drug delivery mechanisms$125,199

Funding body: Cancer Institute NSW

Funding body Cancer Institute NSW
Project Team Associate Professor Christopher Scarlett, Doctor Kathryn Skelding, Doctor Jude Weidenhofer, Doctor Matt Dun, Doctor Kelly Kiejda, Professor Adam McCluskey, Ms Elham Sadeqzadeh, Professor Hubert Hondermarck, Doctor Rick Thorne, Laureate Professor Rodney Scott
Scheme Research Equipment Grant
Role Investigator
Funding Start 2014
Funding Finish 2014
GNo G1400627
Type Of Funding Other Public Sector - State
Category 2OPS
UON Y

JuLI Stage $71,674

Funding body: NHMRC (National Health & Medical Research Council)

Identifying novel therapeutic targets for the treatment of Acute Myeloid Leukaemia$67,539

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Matt Dun, Doctor Nikki Verrills
Scheme Project Grant
Role Lead
Funding Start 2014
Funding Finish 2017
GNo G1301353
Type Of Funding C3120 - Aust Philanthropy
Category 3120
UON Y

Defining the role of shwachman-bodien diamond syndrome protein (SBDS) in PP2A inhibition in acute myeloid leukaemia (AML).$25,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Matt Dun, Doctor Nikki Verrills
Scheme Project Grant
Role Lead
Funding Start 2014
Funding Finish 2014
GNo G1301442
Type Of Funding Grant - Aust Non Government
Category 3AFG
UON Y

20133 grants / $32,096

Proteomics of Cancer$6,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Matt Dun, Doctor Nikki Verrills, Dr Anoop Enjeti
Scheme Project Grant
Role Lead
Funding Start 2013
Funding Finish 2013
GNo G1300054
Type Of Funding Contract - Aust Non Government
Category 3AFC
UON Y

American Association of Cancer Research, Washington Convention Centre Washington DC USA, 6 - 10 April 2012$1,500

Funding body: University of Newcastle - Faculty of Health and Medicine

Funding body University of Newcastle - Faculty of Health and Medicine
Project Team Doctor Matt Dun
Scheme Travel Grant
Role Lead
Funding Start 2013
Funding Finish 2014
GNo G1201225
Type Of Funding Internal
Category INTE
UON Y

20121 grants / $100,000

Hunter Translational Cancer Research Fellowship$100,000

Funding body: Cancer Instititue NSW

Funding body Cancer Instititue NSW
Scheme ...
Role Lead
Funding Start 2012
Funding Finish 2012
GNo
Type Of Funding Aust Competitive - Non Commonwealth
Category 1NS
UON N
Edit

Research Supervision

Number of supervisions

Completed6
Current12

Current Supervision

Commenced Level of Study Research Title Program Supervisor Type
2018 PhD Proteomic Analysis of Blood Based Biomarkers for the Early Detection of Colorectal Heoplasia PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle Principal Supervisor
2018 PhD Targeting Oxidative Stress for the Improved Treatment of Acute Myeloid Leukaemia PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle Principal Supervisor
2018 PhD Proteogenomic Characterisation of Treatment Resistance in Acute Myeloid Leukaemia with Recurring Driver Mutations PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle Principal Supervisor
2018 PhD Investigation into the Anticancer and Complementary Health Benefits PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle Principal Supervisor
2017 PhD Application of a Sensitive, Robust and Quantitative Parallel Reaction Monitoring (PRM) Assay for Measurement of Activated Signalling Pathways in Breast Cancers PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle Co-Supervisor
2017 PhD Molecular Characterisation of Treatment Resistance in Acute Myeloid Leukaemia. PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle Principal Supervisor
2017 PhD A Novel Biomarker and Innovative Therapeutic Strategy for Oesophageal Cancer PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle Co-Supervisor
2016 PhD Reactive Oxygen Species Promoted Leukaemogenesis; Altered Signalling Pathways as New Drug Targets for the Improved Treatment of Acute Myeloid Leukaemia PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle Principal Supervisor
2016 PhD Reduced Expression of Protein Phosphatase 2A Subunit, PPP2R2A and its Role in Breast Cancer PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle Co-Supervisor
2015 PhD Identifying novel therapeutic targets for the treatment of Acute Myeloid Leukaemia PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle Co-Supervisor
2015 PhD PPP2R2A - A Novel Biomarker and Therapeutic Target for Luminal B Breast Cancer PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle Co-Supervisor
2014 PhD Chronic Obstructive Pulmonary Disease (COPD) PhD (Immunology & Microbiol), Faculty of Health and Medicine, The University of Newcastle Co-Supervisor

Past Supervision

Year Level of Study Research Title Program Supervisor Type
2017 Honours Characterisation of low Δ9-tetrahydrocannabinol containing medicinal cannabis for the treatment of acute myeloid leukaemia.
<span style="font-size:12.0pt;font-family:'Arial',sans-serif;">Acute Myeloid Leukaemia (AML) carries a 5-year survival rate of 24%. Current treatments include high dose chemotherapy and bone marrow transplantation; however development of treatment resistance and relapse is common. Cannabis has been used for thousands of years as a traditional medicine and was introduced into western medicine in the nineteenth century. More recently, research into medicinal cannabis has focused on traditional high-THC containing products. Low-THC cannabis is legally defined as having less than 1% &Delta;9-THC and therefore, does not have the phsychotropic effects associated with tradtional cannabis. The aims of this research was to determine whether low-THC cannabis extracts were effective at reducing the survival of AML cells that are sensitive to new precision medicines and AML cells that have formed resistance to these therapies whilst determining whether low-THC cannabis effects the survival of normal healthy cells of the immune system. Two AML cell lines harbouring recurring genetic mutations were used and both show sensitivity to our crude low-THC cannabis extracts. To determine which cannabinoid or unknown chemicals was responsible for the cytotoxic effects we showed, High Performance Liquid Chromatography with Ultraviolet visible light detection (HPLC-UV Vis) was used. During this investigation we have optimised a HPLC-UV Vis technique that resolves thirteen common cannabinoids found in cannabis extracts and used this to analyse what was present in our low-THC containing cannabis extracts. Using various extraction techniques coupled to cytotoxic analysis and HPLC-UV, we have discovered that cannabidiol (CBD) and cannabichromene (CBC) are potentially invovled at inducing cell death of AML cells. Additionally, we have identified an unknown compound whose concentration in each of the extracts reflects the cytotoxicity seen. Future research is still necessary to analyse the unknown compounds and individual activity of compounds, but the research described herein reveals that low-THC containing cannabis is effective at killing AML cells.</span>
Pharmacy, Faculty of Health and Medicine, University of Newcastle Principal Supervisor
2017 Honours Targeting Oxidative Stress for the Improved Treatment of Acute Myeloid Leukaemia
<p style="text-align:justify;line-height:150%;"><span style="font-family:Arial,Helvetica,sans-serif;font-size:small;">Treatment of acute myeloid leukaemia (AML) has remained unchanged over the last 35 years, with standard-of-care chemotherapeutics causing significant side effects and treatment induced death. AML patients often develop resistance to therapies, causing the formation of an even more aggressive untreatable disease that rapidly leads to death. Interest in reactive oxygen species has grown as studies have revealed that high levels of Reactive oxygen species (ROS) are seen in almost all cancer types, including AML. Despite this, the physiological and pathophysiological role that ROS plays in AML has widely remained unknown. It is a possibility that the altered redox environment initiated by the processes of cellular transformation may in fact drive leukaemogenesis. We believe this is through oxidative modifications to crucial regulators of cellular signalling, as well as acquired insults to nucleic acids and lipids, driving increased growth, survival and genomic instability. The altered redox environment may in fact be the cause for the development of drug resistance that is commonly seen during the treatment of an AML patient. These data raise the intriguing possibility of whether ROS may be a novel target for the treatment of AML.</span></p><p style="text-align:justify;line-height:150%;"><span style="font-family:Arial,Helvetica,sans-serif;font-size:small;"><span style="font-size:small;font-family:Arial,Helvetica,sans-serif;">The customary paradigm for the treatment of cancer is to induce ROS formation so that it causes irreversible oxidative damage. Our laboratory has shown that the most common molecular driver of AML, the FLT3 </span><span style="text-decoration:underline;">I</span><span style="font-size:small;font-family:Arial,Helvetica,sans-serif;">nternal </span><span style="text-decoration:underline;">T</span><span style="font-size:small;font-family:Arial,Helvetica,sans-serif;">andem </span><span style="text-decoration:underline;">D</span><span style="font-size:small;font-family:Arial,Helvetica,sans-serif;">uplication (ITD) mutation, leads to cells that produce very high levels of ROS that modify the bone marrow redox microenvironment. Further, using novel and sophisticated proteomics techniques we have shown that AML patients harbouring FLT-ITD+ mutations express proteins showing oxidation of catalytic cysteines in a number of key tumour suppressor proteins such as the protein tyrosine phosphatases (PTPs) which renders them inactive. These novel data may explain the hyperactive activated growth and survival signalling pathways that characterise this subtype of AML. </span></span></p><p style="text-align:justify;line-height:150%;"><span style="font-family:Arial,Helvetica,sans-serif;font-size:small;">The hypothesis for my project is that if we reduce intracellular ROS we may reduce the oxidation of a number of key tumour suppressor proteins we have shown to be inactivated in FLT3-ITD+ AMLs. Through the specific inhibition of ROS production using new FLT3 targeted therapies we will not only inhibit the oncogene responsible for transformation but we will reactivate the negative regulators of the FLT3 pathway, whilst reducing oxidative DNA damage that may help us to overcome issues with resistance and therefore reduce relapse rates and fatalities. </span></p><div><p style="text-align:justify;line-height:150%;"><span style="font-family:Arial,Helvetica,sans-serif;font-size:small;">In the studies described herein, we show that by inhibiting NOX2 we inhibit ROS production. When NOX2 inhibition is combined with FLT3 inhibition, we can induce synergistic cytotoxicity to FLT3-ITD+ AML cells when grown and treated in a model of the bone marrow characterised by low oxygen tension. We also present exciting preliminary mechanistic data showing that the FLT3 regulating PTPs, SHP-1 and DEP-1, are oxidised by ROS produced by NOX2, and that reduced oxidative stress through NOX2 inhibition increased PTP activity by reduced catalytic cysteine oxidation and increased PTP protein expression. </span></p><p style="text-align:justify;line-height:150%;"><span style="font-family:Arial,Helvetica,sans-serif;font-size:small;">The results of my project show NADPH oxidase as a potent source of reactive oxygen species that is responsible for high levels of oxidative stress seen in the most commonly occurring genetic mutation in AML &ndash; FLT3-ITD. ROS produced by the NADPH oxidase-2 complex causes increased DNA damage increasing the genomic instability of these cells and potentially influences the common resistance to therapies that we see. Additionally, my thesis sets the ground-work for a novel treatment paradigm that reduced oxidative stress, which leads to reactivation of intrinsic defence systems that work in cooperation with targeted therapies to synergistically kill AML cells. Finally, the impact of targeting the redox microenvironment in AML and the potential for modulating ROS production for the treatment of AML are discussed, along with the limitations and future directions of this study.</span></p></div><span style="font-size:12.0pt;line-height:150%;font-family:'Times New Roman',serif;"><br clear="all" style="page-break-before:always;" /></span>
Medical Science, Faculty of Health and Medicine, University of Newcastle Principal Supervisor
2016 Honours Prostate cancer: Quantification of proNGF by targeted proteomics
Background. Prostate cancer (PCa) is one of the most prevalent cancers in Australia. The PCa serum biomarker prostate specific antigen (PSA) is used for screening, diagnosis and prognosis, but increasing evidence indicates that PSA testing has serious limitations. Not only does it lack specificity (with false positive and negative detections), but it also fails in identifying the most aggressive forms of PCa that require treatment as compared to the indolent forms of the disease. There is therefore an urgent need for new biomarkers to improve the diagnosis and prognosis of PCa. &nbsp;<br />Preliminary data from our lab have identified the precursor of nerve growth factor (proNGF) as a new potential serum biomarker for PCa. ProNGF expression is increased in cancer cells and positively correlates with PCa aggressiveness. In addition, PCa cells secrete proNGF, and by ELISA increased concentration of proNGF were found in the serum of PCa patients, in particular in case of aggressive tumours. These data suggest that proNGF could be a novel serum biomarker for diagnosis and prognosis of PCa. &nbsp;<br />Aims. This project is focused on developing a targeted proteomic assay (in parallel reaction monitoring - PRM) to reliably quantify proNGF in serum samples. The assay will subsequently be applied for the analysis of PCa serum samples. &nbsp;<br />Methods. After in silico trypsin digestion, two tryptic peptides unique to proNGF were selected with molecular mass and charge appropriate for detection in mass spectrometry. We have obtained the corresponding stable isotope labelled (SIL) peptides and we have established all experimental conditions for their detection in the serum and quantification in PRM mass spectrometry. In particular, we have analysed a series of PCa samples (n=40) of different grade and a series of benign prostatic hyperplasia (BPH, n=20). The results were compared with data obtained by ELISA for proNGF in the same samples. &nbsp;<br />Results. 1. An optimised PRM quantification approach was achieved by analysing twoproNGF SIL peptides LQHSLDTALR and SAPAAAIAAR (by direct injection and in complex serum background). 2. Standard curves for both proNGF SIL peptides in complex serum background were generated and performed to normalise inter-run variability of the mass spectrometer. 3. The average quantity of proNGF endogenous peptide LQHSLDTALR in serum samples was 0.021 &plusmn; 0.050 ng/mL, whereas proNGF endogenous peptide SAPAAAIAAR was undetectable. 4. No significant difference of proNGF peptide LQHSLDTALR quantity was found either between BPH and PCa cancer or across BPH group, low-risk PCa (Gleason 6) and high-risk PCa (Gleason 8 &amp; 9). 5. The correlation factor (r) between PRM data for peptide LQHSLDTALR and the ELISA for proNGF was 0.21, indicating a limited correspondence between data obtained by the two methods. <br />Conclusion. We have developed a PRM based assay for quantifying proNGF in biological samples with a very good specificity/sensitivity (picogram/mL level). However, its use to quantify proNGF in the serum of PCa patients needs further improvements and in particular further optimisation in sample preparation, such as albumin depletion and deglycosylation. Such a PRM assay for proNGF could find biomedical applications beyond PCa, as proNGF has recently been reported to be increased in the cerebrospinal fluid of patients with neurodegenerative disease.&nbsp; <br />6
Medical Science, Faculty of Health and Medicine, University of Newcastle Co-Supervisor
2016 Honours Development of a sensitive, robust and quantitative mass spectrometry assay for the measurement of activated signalling pathways in human breast cancers
<p style="text-align:justify;text-justify:inter-ideograph;line-height:150%;"><span lang="EN-US" style="color:windowtext;">Breast cancer is a major national and global health concern. While the overall survival for breast cancer has significantly improved over the past decades, outcomes for patients with triple negative (TNBC) or Luminal B subtype tumuors remains poor. Recent studies have shown that some TNBCs display inactivation of key DNA damage repair (DDR) pathways which renders them hypersensitive to specific DNA damaging chemotherapy. Whether other breast cancer subtypes also have altered DDR pathways is not known, in part because an effective tool for quantifying the activity of DDR pathways is not available. Therefore, we aimed to develop a robust and sensitive assay to quantitate the activity of DDR pathways in breast cancer.</span><span style="color:windowtext;"> Recent studies indicate that </span><span style="color:windowtext;">a targeted proteomics approach, utilising </span><span style="color:windowtext;">quantitative mass spectrometry-based </span><span style="color:windowtext;">parallel reaction monitoring (PRM), may be a useful technique for identification and quantification of such pathways. PRM is a highly selective and specific method for targeted peptide quantification, including peptides with post-translational modifications such as phosphorylation. It is beginning to be implemented for the quantitative study of changes in protein components within cancer cells. Given that cancer associated signalling pathways are regulated by phosphorylation of key protein mediators, we hypothesized that</span><span style="color:windowtext;"> the development of</span><span style="color:windowtext;"> a multiplexed PRM assay for quantitation of key phosphoproteins involved in activated signalling pathways could be a powerful tool for the identification of activated, and potentially &lsquo;druggable&rsquo; pathways in human breast tumours. </span></p><p style="text-align:justify;text-justify:inter-ideograph;line-height:150%;"><span>Sample preparation is the crucial starting point to obtain high-quality mass spectrometry data, therefore a major focus of this thesis was to determine the optimal sample preparation procedure for PRM-based quantitation of phospho-peptides. To do this,</span><span style="color:windowtext;"> the human breast cancer cell line, </span><span lang="EN-US" style="color:windowtext;">BT474, was </span><span style="color:windowtext;">treated +/- bleomycin to induce double stranded DNA breaks (DSBs) and activate DSB repair pathways. Proteins were extracted in either a sodium carbonate buffer or via the commercially available </span><span lang="EN-US">ProteaseMax<sup>TM</sup></span><span style="color:windowtext;"> kit, and enzymatically digested into peptides using trypsin and lysozyme C, and identified by liquid chromatography tandem mass spectrometry (LC-MS/MS). Analysis of the identified peptides demonstrated </span><span lang="EN-US">enhanced tryptic/Lys C digestion efficiency with the sodium carbonate method, and as such this was used for all subsequent experiments. However, phosphorylated peptides only constituted ~1% of the total peptides identified, and the peak intensity for most phospho-peptides was low, making accurate quantitation difficult. Recent studies have shown <a name="OLE_LINK41">enrichment of phosphopeptides</a> using titanium dioxide chromatography (TiO2) significantly increases the number of phosphoproteins identified in discovery MS projects. Whether phospho-peptide enrichment is required for targeted PRM MS approaches however has not been determined. Therefore, a direct comparison of non-enriched versus phospho-peptide enrichment using a range of TiO2 procedures were performed in the BT474 cells. This resulted in high abundance of non-modified peptides in the non-enriched and flow through lysates, while the majority of phosphopeptides were found in TiO2 eluates. The enrichment enabled improved quantitation of specific phosphopeptides by PRM, and thus confirmed that enrichment with at least one TiO2 step was required for quantitative detection of phosphopeptides. </span></p><p style="text-align:justify;text-justify:inter-ideograph;line-height:150%;"><span lang="EN-US">This optimized procedure was then used to quantitate key phosphoproteins involved in growth, survival and DNA damage repair pathways in breast cancer. </span><span style="color:windowtext;">As a positive control we analysed H2AX, a key marker of DSBs, and as expected found increased phosphorylation of pSer139-H2AX in response to bleomycin. We further found increased phosphorylation of </span><span lang="EN-US" style="color:windowtext;">Protein Kinase B (AKT; Thr307 and Ser473), </span><span style="color:windowtext;">checkpoint kinase 2 (CHK2) at Thr386, and the ataxia-telangiectasia mutated (ATM) protein (double phosphorylation at Y175 and S179). In contrast H2AX doubly phosphorylated at S139/Y140, pThr68-CHK2 and pSer367-ATM was reduced. This provides novel insight into the cellular response to DSBs. Importantly, t</span><span lang="EN-US" style="color:windowtext;">his analysis was achieved from average 2 &micro;g of peptides, therefore we believe this assay will be useful for primary patient tissues and hence may be a powerful approach for identifying activated and druggable pathways in human breast tumuors.</span></p>
Medical Science, Faculty of Health and Medicine, University of Newcastle Co-Supervisor
2015 Honours The Role of Reduced Protein Phosphatase 2A Subunit, PPP2R2A (B55α), Expression in Breast Cancer.
&lt;p style="margin-bottom:0cm;margin-bottom:.0001pt;line-height:150%;"&gt;&lt;span style="font-size:12.0pt;line-height:150%;font-family:'Times New Roman',serif;"&gt;Breast Cancer is a disease of global concern, with current treatments lacking selectivity and not showing a response in many patients. Patients with luminal-B like breast cancers in particular have shown reduced sensitivity to endocrine therapies, and have a more aggressive phenotype similar to Triple Negative breast tumours and worse prognosis than luminal-A like breast tumours. A marker and potential therapeutic target was thus need to distinguish these particular patients, as current methods of classification have been shown to be ineffective, especially in distinguishing between luminal-A and B tumours. Recent studies have shown that reduced expression of the &lt;em&gt;PPP2R2A&lt;/em&gt; gene, encoding the B55a subunit of Protein Phosphatase 2a (PP2A), may be such a marker, with highly reduced expression in a majority of luminal-B tumours studied. Reduced expression of this subunit has been found to impair the DNA damage Homologous Recombination (HR) repair pathway in HeLa cervical cancer cells, and furthermore, reduced B55a expression and impaired DNA damage repair in lung carcinomas was found to sensitise these cells to the PARP inhibitor (PARPi) ABT888, through synthetic lethality. &lt;/span&gt;&lt;/p&gt;&lt;p style="margin-bottom:0cm;margin-bottom:.0001pt;line-height:150%;"&gt;&lt;span style="font-size:12.0pt;line-height:150%;font-family:'Times New Roman',serif;"&gt;&lt;/span&gt;&lt;/p&gt;&lt;p style="margin-bottom:0cm;margin-bottom:.0001pt;line-height:150%;"&gt;&lt;span style="font-size:12.0pt;line-height:150%;font-family:'Times New Roman',serif;"&gt;This study therefore investigated the role reduced B55a expression may play in breast cancer cells, to determine whether this is a potential treatment target for low-B55a expressing luminal-B tumours. It was first hypothesised, based on past studies, that reduced B55a expression in breast cancer cells would impair their DNA damage repair pathways. To investigate this, two B55a knockdown models were created in both&lt;span&gt;&amp;nbsp; &lt;/span&gt;MCF7 and ZR751breast cancer cell lines, as well as a control cell line to compare back to. DNA repair efficiency was then examined by inducing DNA damage via Bleomycin and analysing expression of important HR repair proteins. Changes in expression and phosphorylation mediated activation of many of these proteins, as well as prolonged increase of ɣH2AX (marker for DSBs) in B55a-low cells compared to control cells supported the hypothesis that DN repair was impaired in these B55a-low cells. &lt;/span&gt;&lt;/p&gt;&lt;p style="margin-bottom:0cm;margin-bottom:.0001pt;line-height:150%;"&gt;&lt;span style="font-size:12.0pt;line-height:150%;font-family:'Times New Roman',serif;"&gt;&lt;/span&gt;&lt;/p&gt;&lt;p style="margin-bottom:0cm;margin-bottom:.0001pt;line-height:150%;"&gt;&lt;span style="font-size:12.0pt;line-height:150%;font-family:'Times New Roman',serif;"&gt;It was then hypothesised that impaired DNA repair in B55a-low breast cancer cells would further sensitise these cells to DNA damaging agents. To examine this, B55a knockdown and control cells were treated with DNA damaging agents (ɣ-irradiation, Bleomycin, Cisplatin, ABT888), at various doses. However the hypothesis was not supported, as there was no significantly increased sensitivity to these agents in B55a-low cells compared to the control cells.&lt;/span&gt;&lt;/p&gt;&lt;p style="margin-bottom:0cm;margin-bottom:.0001pt;line-height:150%;"&gt;&lt;span style="font-size:12.0pt;line-height:150%;font-family:'Times New Roman',serif;"&gt;&lt;/span&gt;&lt;/p&gt;&lt;span style="font-size:12.0pt;line-height:107%;font-family:'Times New Roman',serif;"&gt;Therefore while this study suggests that DNA repair may be altered and impaired in B55a-low breast cancer cells (and hence luminal-B tumours), this finding is currently not translatable to use as a potential treatment target for patient with luminal-B tumours. However future studies using altered dosage and time course of DNA damaging agents may find a heightened sensitivity of B55a-low breast cancer cell lines, allowing for specific personalised treatment of patients with aggressive luminal-B tumours, using therapeutics that already currently available. &lt;/span&gt;
Medical Science, Faculty of Health and Medicine, University of Newcastle Co-Supervisor
2014 Honours Investigation of the function of tetraspanins CD9 and CD151 on prostate exosomes
Exosomes are nanosized, membranous vesicles secreted by most cells that have been shown to be important for cellular communication. Whilst most research into exosomes has focussed on their function in a diseased state, such as cancer, their role in normal cellular functioning has not been thoroughly investigated. Tetraspanins are a family of transmembrane proteins, including CD9 and CD151, that are abundantly expressed on exosomes, however, their function within exosomes is yet to be fully elucidated. CD9 and CD151 have opposing roles in many solid tumours, including prostate, where CD9 is typically downregulated and CD151 is typically upregulated and both being indicative of poor prognosis. Therefore, this study was designed to investigate the effects that altered CD9 and CD151 in exosomes have on a normal cellular population, and whether alteration of these tetraspanins can make a normal cell more metastatic.&lt;br /&gt;CD9 and CD151 expression was altered in a normal, non-tumourigenic cell line (RWPE1) to express either low CD9 (CD9 low) or high CD151 (CD151 high). Western blot and flow cytometry were used to confirm that these cell lines displayed altered expression of CD9 and CD151 and that their control lines (Scram and Zeo respectively) displayed similar expression to RWPE1 cells. An invasive and metastatic derivative cell line of RWPE1 cells, WPE1-NB26, was used as a tumourigenic control. Exosomes from these cells were then assessed for their ability to attach to and internalise into RWPE1 cells before being used as treatments for RWPE1 cells in a range of functional assays, including adhesion, proliferation, migration and invasion, to assess whether the altered exosomal expression of CD9 and CD151 can influence these cellular behaviours. Exosomes from RWPE1, CD9 low, CD151 high and WPE1-NB26 cell lines were also analysed using a quantitative mass spectroscopy approach to determine changes in their proteome.&lt;br /&gt;There were no differences observed between exosome populations in regards to attachment and internalisation into RWPE1 cells. Treating RWPE1 cells with exosomes also showed no difference in the proliferation of RWPE1 cells over a 72&lt;br /&gt;6&lt;br /&gt;hour period. RWPE1 cell adhesion to Collagen-IV, Fibronectin and Laminin 1 was assessed and revealed no difference for CD9 low exosome treated cells, however, an increase in adhesion was seen with the CD151 high exosome treated cells at 1 (p = 0.0023) and 4 hours (p = 0.0279). Only CD151 high exosome treated RWPE1 cells showed an increase in migration at 20 (p = 0.0186), 24 (p = 0.0068) and 30 hours (p = 0.0038), however no differences were observed in an invasion assay. Proteomic analysis of exosomes revealed that there were 101 proteins with a greater than 2 fold increase and 18 proteins with a greater than 2 fold decrease in abundance compared to RWPE1 exosomes.&lt;br /&gt;The results of this study suggest that alterations of CD9 and CD151 in exosomes have only limited functional effects on a normal cellular population. This study also identified that altering the expression of CD9 and CD151 in exosomes affects their entire proteome. Further characterisation of the effects of CD9 and CD151 expression in exosomes needs to be performed, utilising a panel of tumourigenic cell lines. Therefore due to the alterations on cellular function upon the addition of CD151 high exosomes, it suggests that modified exosomes could represent a therapeutic strategy for prostate cancer.
Medical Science, Faculty of Health and Medicine, University of Newcastle Co-Supervisor
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Research Collaborations

The map is a representation of a researchers co-authorship with collaborators across the globe. The map displays the number of publications against a country, where there is at least one co-author based in that country. Data is sourced from the University of Newcastle research publication management system (NURO) and may not fully represent the authors complete body of work.

Country Count of Publications
Australia 61
Denmark 8
United States 8
Belgium 5
New Zealand 3
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News

Strengthening the defence against Leukaemia

September 25, 2017

Research from UON has revealed a more targeted way of treating an aggressive type of cancer typically prevalent in children.

$1.5m to Newcastle researchers to unlock cancer secrets

February 21, 2014

Three University of Newcastle cancer researchers have been recognised with Cancer Institute NSW Early Career Fellowships, totalling more than $1.5 million.

Dr Matt Dun

Position

Cancer Institute NSW EC Fellow
Molecular Oncology
School of Biomedical Sciences and Pharmacy
Faculty of Health and Medicine

Contact Details

Email matt.dun@newcastle.edu.au
Phone (02) 4921 5693
Fax (02) 4921 6903

Office

Room LS3.33
Building Life Sciences Building
Location Callaghan
University Drive
Callaghan, NSW 2308
Australia
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