
Dr Heather Murray
Postdoctoral Researcher
School of Biomedical Sciences and Pharmacy
- Email:heather.murray@newcastle.edu.au
- Phone:(02) 4921 6934
Signalling a new future for leukaemia treatment
Despite only recently beginning her research career, Dr Heather Murray has already identified a puzzle piece that could revolutionise the quest for more effective treatment of acute myeloid leukaemia (AML).
Only one in four patients treated for acute myeloid leukaemia (AML), the most aggressive subtype of blood cancer, will survive five years past their diagnosis.
Recent advances in cancer research have improved outcomes, with a focus on genomic-based cell analyses informing customised treatment for each individual patient.
In partnership with key international collaborators, cancer researchers at UON, HMRI and the Hunter Cancer Research Alliance, are taking this research a step further by using proteomics to study proteins, and erroneous signaling, with the hope of identifying potential therapies.
The newest addition to this group of ground breaking collaborators is postdoctoral researcher Dr Heather Murray.
Setting the course
Initially planning a career in pharmacy, Heather found her undergrad degree in biomedical science provided the inspiration to follow a research path.
“In biomed I was exposed to the work of several talented local researchers, and I became interested in the ways that science could be applied to solve biological mysteries and improve treatment outcomes for people suffering with cancer,” Heather explains.
Continuing a study trajectory encompassing undergrad Summer scholarships and an early focus on melanoma, Heather sought out Associate Professor Verrills in a bid to take on a PhD project with maximum translational potential.
“I chose to work on a project researching leukaemia biology because it was different to anything I had done before, and could have massive impact,” Heather says.
Heather was awarded her doctorate by the University of Newcastle in 2020. A postdoctoral research position in the team of Associate Professor Verrills followed.
Heather’s PhD study into a novel therapeutic strategy for AML with mutations in the tyrosine kinase 3 (FLT3) gene, which is mutated in approximately one third of AML cases, has garnered international attention.
A research collaboration between researchers from the University of Newcastle, Hunter Medical Research Institute and Hunter Cancer Research Alliance, and the University of Southern Denmark, Heather is lead author on these findings, recently published in the prestigious international blood cancer journal Leukemia.
Inhibiting AML
In AML, overactive signaling prevents white blood cells from maturing and developing the power to fight infection. Simultaneously, the AML cells divide and grow at accelerated rates, taking over the blood and bone marrow and impeding healthy immune system processes.
Heather hypothesized that identifying unusually active cell proteins could provide invaluable clues to possible targets for therapeutic inhibition.
“I utilised phosphoproteomics to investigate not just whether the protein was there, but I was looking for a phosphorylation state which is a modification on the protein which generally indicates that the protein is active,” Heather says.
“We found that a protein called DNA-PK was highly phosphorylated in mutant FLT3 AML. So that suggested to us that DNA-PK may be highly active in the leukaemia, and therefore targeting DNA-PK would be an effective therapeutic strategy.”
Startling preclinical results suggest that using chemical compounds to simultaneously block the activity of FLT3 and DNA-PK causes the leukaemia cells to die whilst having no effect on normal, healthy cells.
Where to from here
Whilst working toward clinical trials with this new knowledge, Heather and her cancer research collaborators will be looking at whether this combination of inhibitors is relevant in the treatment of other forms of blood cancer, as well as investigating the efficacy of this novel strategy in regard to drug resistance.
“Our working hypothesis is that adding the DNA-PK inhibitor may actually reduce development of resistance,” Heather says.
“We do have funding from the NHMRC to do further work, to look at resistance to the targeted therapies that we’re using and whether we can possibly target pathways to prevent resistance from happening.”
To maximise and streamline experiments using donor cells, the Hunter Leukaemia Program has been established.
“We work closely with clinician researcher Associate Professor Anoop Enjeti, who brings unique insight to our work, making sure we are always working towards taking our work into the clinic,” Heather says.
The collaboration with Dr Enjeti is also crucial to the process of testing potential therapies by facilitating the collection of patient cell donations.
“If a patient arrives to clinic and they consent for some of their sample being used for our research, we can then analyse these cells in the lab and test their response to potential new therapies.”
Heather is dedicated to her research and finds purpose in the possibility of helping those who need effective treatment solutions for leukaemia.
“I find medical research rewarding with the potential to make a difference to peoples’ lives. I am drawn to the problem-solving aspect of research work, whilst the prospect of contributing to improved health and medical treatment in the community also drives my enthusiasm and commitment.”
Signalling a new future for leukaemia treatment
Despite only recently beginning her research career, Dr Heather Murray has already identified a puzzle piece that could revolutionise the quest for more effective treatment of acute myeloid leukaemia (AML).
Career Summary
Biography
Following early work researching DNA repair in melanoma, her research interests are now centred on the use of proteomics for functional characterisation and therapy guidance in cancer, particularly acute leukaemia subtypes.
Dr Murray’s doctoral work was focused on the phosphoproteomic characterisation of FLT3-mutant acute myeloid leukaemia (AML) and the therapeutic targeting of DNA repair in AML. With these findings published in the leading blood cancer journal Leukemia, Dr Murray has transitioned to a postdoctoral research position at the University of Newcastle and Hunter Medical Research Institute in the Molecular Oncology group led by Associate Professor Nikki Verrills. Dr Murray’s current research, in collaboration with field-leading researchers, is focused on combining genomic, proteomic, and phosphoproteomic approaches to characterise acute leukaemia subtypes and identify novel targets for precision therapy. In parallel Dr Murray is involved in pre-clinical testing of novel anti-leukaemic therapies, with the aim of translating the Molecular Oncology group laboratory findings into the clinical trial setting.
In addition to research, Dr Murray has also contributed to the medical research community through her involvement in local scientific committees. She has been involved in organising local scientific meetings, as Chair of the Hunter Cancer Research Alliance Scientific committee 2020, a member of the Hunter Cancer Research Alliance Scientific committee 2018, and Treasurer of the Australian Society for Medical Research Hunter Region Scientific committee 2016-2017. She also co-founded the University of Newcastle Postgraduate Students Association Proteomics Journal Club for which she was Secretary from 2017-2019. Dr Murray is currently a member of the Hunter Cancer Research Alliance Future Leaders Group.
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
Professional Experience
UON Appointment
Title | Organisation / Department |
---|---|
Postdoctoral Researcher | University of Newcastle School of Biomedical Sciences and Pharmacy Australia |
Postdoctoral Researcher | University of Newcastle School of Biomedical Sciences and Pharmacy Australia |
Publications
For publications that are currently unpublished or in-press, details are shown in italics.
Journal article (9 outputs)
Year | Citation | Altmetrics | Link | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
2020 |
Murray HC, Enjeti AK, Kahl RGS, Flanagan HM, Sillar J, Skerrett-Byrne DA, et al., 'Quantitative phosphoproteomics uncovers synergy between DNA-PK and FLT3 inhibitors in acute myeloid leukaemia.', Leukemia, (2020)
|
||||||||||
2020 |
Dun MD, Mannan A, Rigby CJ, Butler S, Toop HD, Beck D, et al., 'Shwachman Bodian Diamond syndrome (SBDS) protein is a direct inhibitor of protein phosphatase 2A (PP2A) activity and overexpressed in acute myeloid leukaemia', Leukemia, 34 3393-3397 (2020) [C1]
|
||||||||||
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]
|
||||||||||
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.
|
||||||||||
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.
|
||||||||||
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.
|
||||||||||
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]
|
||||||||||
Show 6 more journal articles |
Conference (8 outputs)
Year | Citation | Altmetrics | Link | ||
---|---|---|---|---|---|
2020 |
Germon ZP, Sillar JR, Mannan A, Duchatel R, Murray HC, Douglas A, et al., 'Reactive oxygen species in FLT3-ITD+ acute myeloid leukemia contributes to oncogenic signaling and is a novel treatment target', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2020)
|
||||
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)
|
||||
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)
|
||||
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]
|
||||
Show 5 more conferences |
Grants and Funding
Summary
Number of grants | 7 |
---|---|
Total funding | $243,326 |
Click on a grant title below to expand the full details for that specific grant.
20212 grants / $126,996
Cracking the Code: The launch of a genomic, epigenetic and proteomic pre-clinical platform to improve the treatment of paediatric leukemias$122,000
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Associate Professor Matt Dun, Associate Professor Nikki Verrills, Doctor Heather Lee, Doctor Janis Chamberlain, Doctor Frank Alvaro, Doctor Anoop Enjeti, Associate Professor Kathryn Skelding, Doctor Lisa Lincz, Doctor Abdul Mannan, Doctor Heather Murray, Kristy McCarthy, Elizabeth Heskett, Paola Baeza, Kathleen Irish |
Scheme | Research Grant |
Role | Investigator |
Funding Start | 2021 |
Funding Finish | 2021 |
GNo | G2001337 |
Type Of Funding | C3120 - Aust Philanthropy |
Category | 3120 |
UON | Y |
Pilot data for study: Novel therapies for molecular subtypes of acute myeloid leukaemia (AML)$4,996
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Doctor Heather Murray |
Scheme | Research Grant |
Role | Lead |
Funding Start | 2021 |
Funding Finish | 2021 |
GNo | G2100163 |
Type Of Funding | C3120 - Aust Philanthropy |
Category | 3120 |
UON | Y |
20192 grants / $10,300
Preclinical research into the potential applications of GDC-0084 in diffuse intrinsic pontine glioma (DIPG)$10,000
Funding body: Kazia Therapeutics Limited
Funding body | Kazia Therapeutics Limited |
---|---|
Project Team | Associate Professor Matt Dun, Associate Professor David Ziegler, Doctor Heather Murray, Doctor Ryan Duchatel, Doctor Frank Alvaro |
Scheme | Research Grant |
Role | Investigator |
Funding Start | 2019 |
Funding Finish | 2019 |
GNo | G1801161 |
Type Of Funding | C3111 - Aust For profit |
Category | 3111 |
UON | Y |
Australasian Proteomics Society ECR Travel Award$300
Funding body: Australasian Proteomics Society
Funding body | Australasian Proteomics Society |
---|---|
Scheme | The Human Proteome Organisation Conference 2019 Awards |
Role | Lead |
Funding Start | 2019 |
Funding Finish | 2019 |
GNo | |
Type Of Funding | External |
Category | EXTE |
UON | N |
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 | Associate Professor Matt Dun, Doctor Frank Alvaro, Doctor Ryan Duchatel, Doctor Heather Murray, Associate Professor David Ziegler |
Scheme | Postdoctoral fellowship |
Role | Investigator |
Funding Start | 2018 |
Funding Finish | 2020 |
GNo | G1801130 |
Type Of Funding | C3120 - Aust Philanthropy |
Category | 3120 |
UON | Y |
20172 grants / $6,030
HCRA Biomarkers and Targeted Therapies flagship RHD student grant$5,000
Funding body: HCRA Hunter Cancer Research Alliance
Funding body | HCRA Hunter Cancer Research Alliance |
---|---|
Scheme | Research Project |
Role | Lead |
Funding Start | 2017 |
Funding Finish | 2017 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
European Society of Molecular Oncology travel award$1,030
Funding body: ESMO
Funding body | ESMO |
---|---|
Scheme | ESMO Signaling Pathways Symposium 2017 |
Role | Lead |
Funding Start | 2017 |
Funding Finish | 2017 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
Research Supervision
Number of supervisions
Past Supervision
Year | Level of Study | Research Title | Program | Supervisor Type |
---|---|---|---|---|
2020 | Honours |
Pre-clinical testing of a novel anti-cancer therapy <p>Bachelor of Biomedical Science (Hons)</p> |
Biochemistry & Cell Biology, University of Newcastle | Co-Supervisor |
2020 | Honours |
Precision medicine for acute myeloid leukaemia Bachelor of Pharmacy (Hons) |
Biochemistry & Cell Biology, The University of Newcastle | Co-Supervisor |
News
New treatment idea discovered for leukaemia
November 2, 2020
Dr Heather Murray
Position
Postdoctoral Researcher
School of Biomedical Sciences and Pharmacy
College of Health, Medicine and Wellbeing
Contact Details
heather.murray@newcastle.edu.au | |
Phone | (02) 4921 6934 |
Link | Research Networks |
Office
Room | LS3-37 |
---|---|
Building | Life Sciences |
Location | Callaghan University Drive Callaghan, NSW 2308 Australia |