Dr Moira Graves

Dr Moira Graves

Post-Doctoral Researcher

School of Medicine and Public Health

Finding answers to cancer’s complex problems

Dr Moira Graves always hoped to forge a career in research, and now she’s found a home in a team who like ‘poking a problem’ as much as she does.

Dr Moira Graves

Moira started her career in pathology, but there was always a part of her that was drawn to research. After spending a number of years working around Australia, Moira moved to Newcastle and found her research niche.

“Once my boys were in school, I thought about what I really, really wanted to do, and I realised that I’d always wanted to do research.” After completing a Masters at the University of Sydney, Moira had the chance to work with Laureate Professor Rodney Scott in his genetics lab. This led to a PhD in Multiple Sclerosis, and where Moira immersed herself in the complexities of genetics research.

However, it was family that really helped her decide her research path. “Toward the end of my PhD candidature my brother called me and told me he had a recurrent pain in his upper leg, he said it felt like a big orange – so I told him he had to go straight to a Doctor and get an MRI,” Moira says.

“He was diagnosed with stage four metastatic melanoma. The orange-sized lump was a cancer tumour, and it had spread to his lymph nodes, his liver and his lungs. They basically sent him home and gave him six months to live.”

However, upon seeking the advice of her work mates, Moira found out about an innovative clinical trial in melanoma. “So I got on the phone and told him to catch a plane from Townsville to Sydney,” Moira adds. “He ended up being one of the first people to go on this clinical trial with two new drugs which were BRAF/Mekinhibitors. Within a few months the cancer had shrunk down to the size of a golf ball, and in 12 months it was gone. He was one of the first people in Australia who had more than five years response to that treatment.”

This experience set Moira on a determined path. “Because of where he lived, he was basically told to go home and die. If you didn’t live in Sydney or Melbourne, you didn’t have the option to enroll in a clinical trial and have the best chance to live.”

Moira joined Associate Professor Nikola Bowden’s team at HMRI and they started working on treatment-resistant melanoma. Since 2015, they’ve developed two trials for people who initially respond to treatment, but then develop a resistance and relapse.

“We’re working on a way to re-prime their immune system so they can go back on a drug that was working to fight the cancer,” Moira says.

Cancer is a complex beast, and melanoma is particularly challenging. “When I first started working with Nikola, we tried to work out how melanoma cells are so good at evading the immune system. They’re experts at it. We needed to find a way to make those tumour cells have little lights on the outside that say, ‘here I am, come and get me’.”

Working with two off-patent drugs (which are readily available, and cheap to buy) the team uncovered that these drugs could encourage the DNA to create an abnormal protein that served as a little light that made the cells identifiable as abnormal.

“Once the immune system recognises something as abnormal, it attacks it, but cancer cells are skilled as disguising themselves and blending in with the body,” Moira says. “Melanoma is basically the body’s response to damage, and the DNA mutates because of UV damage. So we’re working with the body to get the immune system to work to repair DNA – and take out the tumour’s advantage so the body can repair naturally.”

Switching focus to the brain

Moira is now transferring her knowledge to another complex cancer, glioblastoma – one of the most deadly forms of brain cancer. “Working with the team, we’ve partnered with Merck on Melanoma, and because we’re working on DNA repair, they thought we could trial these drugs on glioblastoma,” Moira explains.

The drugs were developed to treat another form of cancer, but after many stages of trials the company discovered that these drugs were no more effective at treating the cancer than existing treatments. So Moira and the team sat down, looked at what the drugs were doing in the body and looked to repurpose them for brain cancer and ovarian cancer.

“These two cancers have very few, if any, effective treatments once they relapsed past a certain treatment,” Moira explains. “I put in for an HMRI grant, which we were awarded, and we started working with these drugs and brain cancer cell lines. We got some promising new data that showed that combining these new drugs with the old treatment actually increased the cell death in these tumour cells.”

“We applied to the Mark Hughes Foundation and was awarded a grant of $200 000 and a PhD student named Mat is working on it. He has shown that after the brain cancer patient relapses and the tumour comes back, the tumour is  not as sensitive to the drug they were first using. So what we’re doing is seeing whether combining a new DNA inhibitor with this existing drug makes the treatment more effective.”

“We’ve been working with the radiation team down at Lake Macquarie Private and we think we have found a new job for one of the four Merck drugs were trialing,” Moira says. “When combining the new drug with the old drug after radiation, the tumour cells started to die more effectively. These new drugs have already gone through phase 1 trials, so we know about the expected side effects, so the time to a clinical trial is much shorter. Hopefully a clinical trial for brain cancer could start in 2021.”

One of the things that Moira enjoys most about her job is problem solving, and she’s found herself in the ideal team to do so. “You’ve got to find people who are not the same as you, and who’ll come at a problem from a different angle,” Moira says. “We’ll throw ideas around, poke them and prod them, and then we’ll go into the lab and see if it’s going to work. I like being challenged.”

The work Moira’s doing comes at cancer from a different angle. “I don’t think you can ever eradicate cancer, because cancer is actually a part of you,” Moira explains. “If you try to kill every single tumour cell with aggressive treatment, your quality of life will be poor. What we want to do, is help people live a good quality life, go back to work, and live with their cancer so it’s more like a chronic disease than a death sentence.”

“We won’t eradicate it, but we will contain it so you can live the life you have chosen to lead.”

Dr Moira Graves

Finding answers to cancer’s complex problems

Dr Moira Graves always hoped to forge a career in research, and now she’s found a home in a team who like ‘poking a problem’ as much as she does.

Read more

Career Summary

Biography

Dr Moira Graves completed her doctorate in 2015. In my thesis, I examined DNA methylation (the ”stop” signs on DNA expression) in key genes and multiple sclerosis risk in individual cell populations. This was the first time that specific T and B cell populations were examined in a epigenetic study in MS populations.

I accepted an opportunity to work with Associate Professor Nikola Bowden and  now use my knowledge in DNA methylation in immune cells to apply to melanoma research.  My current research examines immune cells populations in metastatic melanoma patients who have relapsed on immunotherapy.  I also examine the pharmacokinetics of anti-PD-1 therapy in patients with metastatic melanoma.

What are your research interests?

  • Investigating why some patients with metastatic melanoma respond to the new treatment, immunotherapy, and why others do not
  • Understanding the process where the body can identify a cancer is foreign but is unable to destroy it
  • Using drugs that are off patent (ie cheap) to “reboot” a patient’s immune system to identify that the cancer they have is foreign and to destroy it.

Why did you get into research?

I am from a family of nine – I have four brothers and four sisters.  Six of the nine siblings have had stage 1 melanomas removed and my brother was diagnosed with metastatic melanoma.  The reason he is alive and well is that he was part of clinical trials. Clinical trials have given my brother another chance at life and my wish is that other families is have that chance to live.

My ultimate goal is to see patients with metastatic melanoma enjoy a good quality of life with treatment that will prolong life with minimal side effects. It would make cancer part of a person’s life journey, not the end the journey.

Future Focus

I would like my research in future to concentrate on the individual patient with melanoma as future treatments will be dedicated to the individual.  Just as your immune system is unique to you so will your cancer treatment.


Qualifications

  • Doctor of Philosophy, University of Newcastle
  • Bachelor of Applied Science (Medical Lab Science), Queensland Institute of Technology
  • Graduate Diploma in Management Studies, University of Southern Queensland

Keywords

  • Cancer Genetics
  • Immunotherapy
  • Melanoma

Fields of Research

Code Description Percentage
310504 Epigenetics (incl. genome methylation and epigenomics) 30
310505 Gene expression (incl. microarray and other genome-wide approaches) 30
310507 Genetic immunology 40

Professional Experience

UON Appointment

Title Organisation / Department
Post-Doctoral Researcher University of Newcastle
School of Medicine and Public Health
Australia
Post-Doctoral Researcher University of Newcastle
School of Medicine and Public Health
Australia
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Publications

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


Journal article (9 outputs)

Year Citation Altmetrics Link
2021 Lozinski M, Bowden NA, Graves MC, Fay M, Tooney PA, 'DNA damage repair in glioblastoma: current perspectives on its role in tumour progression, treatment resistance and PIKKing potential therapeutic targets', CELLULAR ONCOLOGY, (2021)
DOI 10.1007/s13402-021-00613-0
Co-authors Michael Fay, Paul Tooney, Nikola Bowden
2021 Navani V, Graves MC, Marchett GC, Mandaliya H, Bowden NA, van der Westhuizen A, 'Overall survival in metastatic melanoma correlates with pembrolizumab exposure and T cell exhaustion markers.', Pharmacol Res Perspect, 9 e00808 (2021)
DOI 10.1002/prp2.808
Co-authors Nikola Bowden, Hiren Mandaliya
2020 Van Der Westhuizen A, Knoblauch N, Graves M, Levy R, Hesson L, Vilain R, Bowden N, 'Sequential Decitabine and Carboplatin Induced Stabilisation of Tumour Burden in a Patient with Immunotherapy-Resistant Metastatic Melanoma', Clinical Oncology Case Reports, 3 (2020)
DOI 10.37532/cocr.2020.3(5).147
Co-authors Nikola Bowden
2020 Navani V, Graves MC, Bowden NA, Van Der Westhuizen A, 'Immune checkpoint blockade in solid organ tumours: Choice, dose and predictors of response', British Journal of Clinical Pharmacology, 86 1736-1752 (2020) [C1]

Immune checkpoint blockade has transformed outcomes across solid organ tumours. Monoclonal antibodies targeting the negative inhibitory cytotoxic T lymphocyte-associated protein 4... [more]

Immune checkpoint blockade has transformed outcomes across solid organ tumours. Monoclonal antibodies targeting the negative inhibitory cytotoxic T lymphocyte-associated protein 4 and programmed-death 1/programmed death-ligand 1 axis can lead to deep and durable responses across several tumour streams in the advanced setting. This immunotherapy approach is increasingly used earlier in the treatment paradigm. A rapidly evolving regulatory, reimbursement and drug development landscape has accompanied this novel class of immunotherapy. Unfortunately, only a small proportion of patients respond meaningfully to these agents. Here we review how the underlying tumoural genomic, histological and immunological characteristics interact within various patient phenotypes, leading to variations in response to checkpoint blockade. Concurrently, we outline the clinical trial and real-world evidence that allows for appropriate selection of agent, dose and schedule in solid organ malignancies. An exploration of current trends in basic and translational research in immune checkpoint blockade accompanies a commentary on future clinical directions for checkpoint blockade in oncology.

DOI 10.1111/bcp.14352
Citations Scopus - 2Web of Science - 2
Co-authors Nikola Bowden
2020 van der Westhuizen A, Knoblauch N, Graves MC, Levy R, Vilain RE, Bowden NA, 'Pilot early phase II study of decitabine and carboplatin in patients with advanced melanoma', MEDICINE, 99 (2020)
DOI 10.1097/MD.0000000000020705
Co-authors Nikola Bowden
2019 Graves M, CelliMarchett G, van Zyl B, Tang D, Vilain RE, van der Westhuizen A, Bowden NA, 'Monitoring Patient Response to Pembrolizumab With Peripheral Blood Exhaustion Marker Profiles', FRONTIERS IN MEDICINE, 6 (2019) [C1]
DOI 10.3389/fmed.2019.00113
Citations Web of Science - 8
Co-authors Nikola Bowden
2018 Maltby VE, Lea RA, Graves MC, Sanders KA, Benton MC, Tajouri L, et al., 'Genome-wide DNA methylation changes in CD19+ B cells from relapsing-remitting multiple sclerosis patients.', Scientific reports, 8 (2018) [C1]
DOI 10.1038/s41598-018-35603-0
Citations Scopus - 17Web of Science - 18
Co-authors Vicki E Maltby, Rodney Scott, Jeannette Lechnerscott
2015 Maltby VE, Graves MC, Lea RA, Benton MC, Sanders KA, Tajouri L, et al., 'Genome-wide DNA methylation profiling of CD8+T cells shows a distinct epigenetic signature to CD4+T cells in multiple sclerosis patients', CLINICAL EPIGENETICS, 7 (2015) [C1]
DOI 10.1186/s13148-015-0152-7
Citations Scopus - 50Web of Science - 47
Co-authors Rodney Scott, Vicki E Maltby, Jeannette Lechnerscott
2014 Graves MC, Benton M, Lea RA, Boyle M, Tajouri L, Macartney-Coxson D, et al., 'Methylation differences at the HLA-DRB1 locus in CD4+ T-Cells are associated with multiple sclerosis', Multiple Sclerosis Journal, 20 1033-1041 (2014) [C1]

Background: Multiple sclerosis (MS) is thought to be caused by T-cell mediated autoimmune dysfunction. Risk ofdeveloping MS is influenced by environmental and genetic factors. Mod... [more]

Background: Multiple sclerosis (MS) is thought to be caused by T-cell mediated autoimmune dysfunction. Risk ofdeveloping MS is influenced by environmental and genetic factors. Modifiable differences in DNA methylation arerecognized as epigenetic contributors to MS risk and may provide a valuable link between environmental exposure andinherited genetic systems.Objectives and methods: To identify methylation changes associated with MS, we performed a genome-wide DNAmethylation analysis of CD4+ T cells from 30 patients with relapsing-remitting MS and 28 healthy controls using Illumina450K methylation arrays.Results: A striking differential methylation signal was observed at chr. 6p21, with a peak signal at HLA-DRB1. Afterprioritisation, we identified a panel of 74 CpGs associated with MS in this cohort. Most notably we found evidence of amajor effect CpG island in DRB1 in MS cases (pFDR <3 x 10<sup>-3</sup>). In addition, we found 55 non-HLA CpGs that exhibiteddifferential methylation, many of which localise to genes previously linked to MS.Conclusions: Our findings provide the first evidence for association of DNA methylation at HLA-DRB1 in relation toMS risk. Further studies are now warranted to validate and understand how these findings are involved in MS pathology. © The Author(s) 2013.

DOI 10.1177/1352458513516529
Citations Scopus - 83Web of Science - 78
Co-authors Rodney Scott, Jeannette Lechnerscott
Show 6 more journal articles

Conference (9 outputs)

Year Citation Altmetrics Link
2019 Van Der Westhuizen A, Vilain R, Graves M, Mandaliya H, Cornall K, Levy R, et al., 'PRIME002: Early phase II study of Azacitidine and Carboplatin priming for Avelumab in patients with advanced melanoma who are resistant to immunotherapy', Salt Lake City, UT, USA (2019)
Co-authors Nikola Bowden, Hiren Mandaliya
2019 Budden T, Graves M, Wong M, Vilain R, Van Der Westhuizen A, Bowden N, 'Repurposing chemotherapy to alter methylation, DNA repair and immune pathways to prime treatment-resistant melanoma for immunotherapy', Salt Lake City, UT, USA (2019)
Co-authors Nikola Bowden
2019 Graves M, Galettis P, Navani V, Van Der Westhuizen A, Bowden N, 'Detecting plasma pembrolizumab concentrations in patients with melanoma using Liquid Chromatography/Mass Spectrometry', Salt Lake City, UT, USA (2019)
Co-authors Peter Galettis, Nikola Bowden
2019 Van Der Westhuizen A, Graves M, Levy R, Majid A, Vilain R, Bowden N, 'PRIME002: Early phase II study of azacitidine and carboplatin priming for avelumab in patients with advanced melanoma who are resistant to immunotherapy', ANNALS OF ONCOLOGY, Barcelona, SPAIN (2019)
Co-authors Nikola Bowden
2018 Graves M, Celli Marchett G, Van Zyl B, Tang D, Vilain R, Van Der Westhuizen A, Bowden N, 'The presence of CXCR6 on CD8+ T cells a biomarker for poor treatment outcomes in metastatic melanoma patients on Pembrolizumab?', Melbourne, VIC, Australia (2018)
Co-authors Nikola Bowden
2018 Graves M, Celli Marchett G, Van Zyl B, Tang D, Vilain R, Van Der Westhuizen A, Bowden N, 'The presence of CXCR6 on CD8+ T cells in metastatic melanoma patients on pembrolizumab correlated with poor treatment outcomes.', Manchester UK (2018)
DOI 10.1111/pcmr.12738
Co-authors Nikola Bowden
2015 Maltby V, Graves M, Lea R, Benton M, Sanders K, Lechner-Scott J, et al., 'Minor methylation differences at various loci in CD8+T-Cells are associated with multiple sclerosis', MULTIPLE SCLEROSIS JOURNAL (2015) [E3]
Co-authors Rodney Scott, Vicki E Maltby, Jeannette Lechnerscott
2014 Graves MC, Ribbons K, Lea R, Vucic S, Shaw CP, Broadley S, et al., 'Do disease modifying treatments affect cognitive performance in early multiple sclerosis?', MULTIPLE SCLEROSIS JOURNAL, Boston, MA (2014) [E3]
Co-authors Peter Schofield, Jeannette Lechnerscott
2014 Graves MC, Benton M, Lea R, Macartney D, Tajouri L, Scott RJ, Lechner-Scott J, 'Epigenetic changes in CD8(+) T cells and CD19(+) B cells isolated from relapsing/remitting multiple sclerosis patients', MULTIPLE SCLEROSIS JOURNAL, Boston, MA (2014) [E3]
Co-authors Jeannette Lechnerscott, Rodney Scott
Show 6 more conferences
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Grants and Funding

Summary

Number of grants 7
Total funding $699,319

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


20193 grants / $519,319

Early phase high throughput studies of cannabinoids using new understandings of glioblastoma biology, radiobiology and pharmacology$190,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Professor Jennifer Martin, Doctor Michael Fay, Doctor James Lynam, Doctor Catherine Lucas, Doctor Peter Galettis, Associate Professor Nikola Bowden, Associate Professor Jenny Schneider, Associate Professor Paul Tooney, Doctor Ross Norris, Doctor Moira Graves
Scheme Project Grant
Role Investigator
Funding Start 2019
Funding Finish 2021
GNo G1900511
Type Of Funding C3300 – Aust Philanthropy
Category 3300
UON Y

PRIME002: Early phase II study of Azacitidine and Carboplatin priming for Avelumab in patients with advanced melanoma who are resistant to immunotherapy$180,000

Funding body: Merck Group

Funding body Merck Group
Project Team Associate Professor Nikola Bowden, Associate Professor Nikola Bowden, Doctor Moira Graves, Mr Ricardo Vilain, Dr Andre van der Westhuizen, Dr Andre van der Westhuizen
Scheme Investigator Sponsor Trials
Role Investigator
Funding Start 2019
Funding Finish 2021
GNo G1801426
Type Of Funding C3400 – International For Profit
Category 3400
UON Y

Can we target PSMA to effectively treat recurrent glioblastoma?$149,319

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Michael Fay, Associate Professor Paul Tooney, Associate Professor Nikola Bowden, Doctor Moira Graves, Dr Thomas Robertson
Scheme Project Grant
Role Investigator
Funding Start 2019
Funding Finish 2019
GNo G1901139
Type Of Funding C3200 – Aust Not-for Profit
Category 3200
UON Y

20184 grants / $180,000

Repurposing traditional chemotherapy to prime advanced melanoma for immune therapy$100,000

Funding body: Maitland Cancer Appeal Committee

Funding body Maitland Cancer Appeal Committee
Project Team Associate Professor Nikola Bowden, Doctor Moira Graves
Scheme Research Project
Role Investigator
Funding Start 2018
Funding Finish 2018
GNo G1701600
Type Of Funding C3300 – Aust Philanthropy
Category 3300
UON Y

Finding new treatment options for brain tumors with DNA repair inhibitors$30,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Moira Graves, Doctor Jennette Sakoff, Doctor Michael Fay, Associate Professor Paul Tooney, Associate Professor Nikola Bowden
Scheme Project Grant
Role Lead
Funding Start 2018
Funding Finish 2019
GNo G1801321
Type Of Funding C3200 – Aust Not-for Profit
Category 3200
UON Y

Do white blood cells from the bone marrow play a role in regrowth of glioblastoma and can blocking their movement into the brain improve treatment?$30,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Moira Graves, Associate Professor Nikola Bowden, Doctor Michelle Brown
Scheme Research Grant
Role Lead
Funding Start 2018
Funding Finish 2020
GNo G1901577
Type Of Funding C3300 – Aust Philanthropy
Category 3300
UON Y

Standard doses of anti-PD-1 immunotherapy for metastatic melanoma may not be sufficient for all patients and may influence patient response to therapy$20,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Associate Professor Nikola Bowden, Doctor Moira Graves, Dr Andre van der Westhuizen, Mr Ricardo Vilain, Doctor Peter Galettis
Scheme Project Grant
Role Investigator
Funding Start 2018
Funding Finish 2018
GNo G1801346
Type Of Funding C3300 – Aust Philanthropy
Category 3300
UON Y
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Research Supervision

Number of supervisions

Completed0
Current3

Current Supervision

Commenced Level of Study Research Title Program Supervisor Type
2020 PhD Brain Cancer and Cannabinoids PhD (Clinical Pharm), College of Health, Medicine and Wellbeing, The University of Newcastle Co-Supervisor
2020 PhD Investigation of the Immune System and the Tumour Microenvironment in Glioblastoma PhD (Experimental Pharmacol), College of Health, Medicine and Wellbeing, The University of Newcastle Co-Supervisor
2019 PhD Will DNA Repair Inhibitors Improve Survival of Patients with Brain Cancer? PhD (Experimental Pharmacol), College of Health, Medicine and Wellbeing, The University of Newcastle Co-Supervisor
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Dr Moira Graves

Position

Post-Doctoral Researcher
DNA Repair Group
School of Medicine and Public Health
College of Health, Medicine and Wellbeing

Contact Details

Email moira.graves@newcastle.edu.au
Phone E(02) 40420284

Office

Room HMRI West wing
Building HMRI
Location HMRI

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