Dr Heather Murray

Dr Heather Murray

Postdoctoral Researcher

School of Biomedical Sciences and Pharmacy

Career Summary

Biography

My research interests are centred on the use of proteomics for functional characterisation and therapy guidance in cancer, particularly acute leukaemia subtypes. I completed my PhD at The University of Newcastle in 2020; my doctoral research was focused on the phosphoproteomic characterisation of Acute Myeloid Leukaemia (AML) and the therapeutic targeting of DNA repair in AML. I am currently a post-doctoral researcher at the University of Newcastle and Hunter Medical Research Institute under the supervision of A/Prof Nikki Verrills. 

Qualifications

  • Doctor of Philosophy in Medical Biochemistry, University of Newcastle
  • Bachelor of Biological Science, University of Newcastle
  • Bachelor of Biomedical Sciences (Hons), University of Newcastle
  • Master of Philosophy, University of Newcastle

Keywords

  • Cancer
  • DNA repair
  • Leukaemia
  • Proteomics

Fields of Research

Code Description Percentage
111201 Cancer Cell Biology 70
110106 Medical Biochemistry: Proteins and Peptides (incl. Medical Proteomics) 30

Professional Experience

UON Appointment

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

For publications that are currently unpublished or in-press, details are shown in italics.


Journal article (7 outputs)

Year Citation Altmetrics Link
2020 Dun MD, Mannan A, Rigby CJ, Butler S, Toop HD, Beck D, et al., 'Shwachman Bodian Diamond syndrome (SBDS) protein is a direct inhibitor of protein phosphatase 2A (PP2A) activity and overexpressed in acute myeloid leukaemia', Leukemia, (2020)
DOI 10.1038/s41375-020-0814-0
Co-authors David Skerrett-Byrne, Hubert Hondermarck, Nikki Verrills, Geoffry DeiuliIs, Matt Dun, Ryan Duchatel, Brett Nixon, Anoop Enjeti, Sam Faulkner
2018 Staudt D, Murray HC, McLachlan T, Alvaro F, Enjeti AK, Verrills NM, Dun MD, 'Targeting Oncogenic Signaling in Mutant FLT3 Acute Myeloid Leukemia: The Path to Least Resistance', INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 19 (2018) [C1]
DOI 10.3390/ijms19103198
Citations Scopus - 19Web of Science - 15
Co-authors Anoop Enjeti, Nikki Verrills, Matt Dun
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 (vol 32, pg 788, 2018)', LEUKEMIA, 32 2731-2731 (2018)
DOI 10.1038/s41375-018-0241-7
Co-authors Matt Dun, Nikki Verrills, David Skerrett-Byrne
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 - 23Web of Science - 21
Co-authors David Skerrett-Byrne, Matt Dun, Nikki Verrills
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 - 7Web of Science - 6
Co-authors Matt Dun, Nikki Verrills
2016 Murray HC, Maltby VE, Smith DW, Bowden NA, 'Nucleotide excision repair deficiency in melanoma in response to UVA', Experimental Hematology and Oncology, 5 (2016) [C1]

© 2016 Murray et al. Background: The causative link between UV exposure and melanoma development is well known, however the mechanistic relationship remains incompletely character... [more]

© 2016 Murray et al. Background: The causative link between UV exposure and melanoma development is well known, however the mechanistic relationship remains incompletely characterised. UVA and UVB components of sunlight are implicated in melanomagenesis; however the majority of studies have focused on the effects of UVB and UVC light. Interestingly, melanoma tumour sequencing has revealed an overrepresentation of mutations signature of unrepaired UV-induced DNA damage. Repair of UVA-induced DNA damage is thought to occur primarily through the Nucleotide Excision Repair (NER) pathway, which recognises and repairs damage either coupled to transcription (Transcription Coupled Repair; TCR), or through global genome scanning (Global Genome Repair; GGR). Current literature suggests NER is deficient in melanoma, however the cause of this remains unknown; and whether reduced NER activity in response to UVA may be involved in melanoma development remains uncharacterised. In this study we aimed to determine if melanoma cells exhibit reduced levels of NER activity in response to UVA. Methods: Melanocyte and melanoma cell lines were UVA-irradiated, and DNA damage levels assessed by immunodetection of Cyclobutane Pyrimidine Dimer (CPD) and (6-4) Photoproduct [(6-4)PP] lesions. Expression of NER pathway components and p53 following UVA treatment was quantified by qPCR and western blot. Results: UVA did not induce detectable induction of (6-4)PP lesions, consistent with previous studies. Repair of CPDs induced by UVA was initiated at 4 h and complete within 48 h in normal melanocytes, whereas repair initiation was delayed to 24 h and >40 % of lesions remained in melanoma cell lines at 48 h. This was coupled with a delayed and reduced induction of GGR component XPC in melanoma cells, independent of p53. Conclusion: These findings support that NER activity is reduced in melanoma cells due to deficient GGR. Further investigation into the role of NER in UVA-induced melanomagenesis is warranted and may have implications for melanoma treatment.

DOI 10.1186/s40164-016-0035-4
Citations Scopus - 12Web of Science - 11
Co-authors Vicki E Maltby, Nikola Bowden, Douglas Smith
2013 Bowden NA, Ashton KA, Vilain RE, Avery-Kiejda KA, Davey RJ, Murray HC, et al., 'Regulators of Global Genome Repair Do Not Respond to DNA Damaging Therapy but Correlate with Survival in Melanoma', PLOS ONE, 8 (2013) [C1]
DOI 10.1371/journal.pone.0070424
Citations Scopus - 6Web of Science - 7
Co-authors Rodney Scott, Xu Zhang, Kelly Kiejda, Nikola Bowden
Show 4 more journal articles

Conference (7 outputs)

Year Citation Altmetrics Link
2019 Murray HC, Enjeti AK, Kahl RGS, Flanagan HM, Dun MD, Verrills NM, 'Phosphoproteomic Characterisation of Acute Myeloid Leukaemia (AML)', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2019)
Co-authors Anoop Enjeti, Nikki Verrills, Matt Dun
2018 Verrills N, Mannan A, Panicker N, Chen Y, Coutman M, Murray H, et al., 'Translating Fundamental Biology into a New Treatment for Therapy-Resistant Breast Cancer: Bench to Bedside and (almost) Back Again!', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2018)
Co-authors Severine Roselli, Nikki Verrills, Matt Dun
2018 Murray H, Enjeti AK, Kahl R, Flanagan H, Verrills N, Dun M, 'Combinatorial Targeting of the c-KIT Receptor Tyrosine Kinase in Acute Myeloid Leukemia', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2018)
Co-authors Matt Dun, Nikki Verrills, Anoop Enjeti
2018 Mclachlan T, Murray H, Skerrett-Byrne D, Dubois O, Withers K, Verrills N, Dun M, 'Molecular Characterization of Treatment Resistance in FLT3 Mutant Pediatric Acute Myeloid Leukemia', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2018)
Co-authors Nikki Verrills, David Skerrett-Byrne, Matt Dun
2018 Germon Z, Sillar J, Murray H, Duchatel R, Al-mazi J, Verrills N, Dun M, 'Intracellular Oxidative Stress Modulates FLT3 Regulatory Proteins Contributing to Oncogenic Signaling in Acute Myeloid Leukemia', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2018)
Co-authors Ryan Duchatel, Nikki Verrills, Matt Dun
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)
Citations Web of Science - 1
Co-authors Matt Dun, 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 Matt Dun, Nikki Verrills, Anoop Enjeti
Show 4 more conferences
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Grants and Funding

Summary

Number of grants 2
Total funding $110,000

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


20191 grants / $10,000

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

Funding body: Kazia Therapeutics Limited

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

20181 grants / $100,000

Proteomic architecture of diffuse pontine intrinsic glioma$100,000

Funding body: McDonald Jones Charitable Foundation

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

Number of supervisions

Completed0
Current1

Current Supervision

Commenced Level of Study Research Title Program Supervisor Type
2020 PhD Investigation of DNA Repair Pathways for Precision Medicine in Acute Myeloid Leukaemia PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle Co-Supervisor
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Dr Heather Murray

Position

Postdoctoral Researcher
School of Biomedical Sciences and Pharmacy
Faculty of Health and Medicine

Contact Details

Email heather.murray@newcastle.edu.au
Phone (02) 4921 7954
Link Research Networks

Office

Room LS3-04
Building Life Sciences
Location Callaghan
University Drive
Callaghan, NSW 2308
Australia
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