Staff Profile

Current position

Aug 2023-current: Research Associate (Data Scientist) in the Paediatric Brain Tumour Group, Newcastle University

PI: Professor Steve Clifford

Themes

Primary: Precision Medicine, Genomics and Informatics

Secondary: Applied Cancer Therapeutics and Outcomes

Tertiary: Chromosome Biology and the Cell Cycle

Previous positions

Dec 2018-Jul 2023: Research Associate in the Leukaemia Research Cytogenetics Group, Newcastle University

PI: Professor Christine Harrison

Qualifications

PhD, Molecular Paediatric Oncology, 2018, Newcastle University

MRes, Medical Genetics (Distinction), 2014, Newcastle University

BSc (Hons) Human Genetics (First class), 2013, Newcastle University

Honours and awards

• November 2022: Children’s Cancer and Leukaemia group and the Little Princess Trust Project Grant. Two year duration (£188,962.00). In collaboration with Professor Christine Harrison. Project title: “Novel drug treatments through repurposing of FDA-approved drugs for improved treatment of high-risk acute lymphoblastic leukaemia”.
• December 2018: British Association for Cancer Research Travel Grant (£1000). To fund attendance of the American Society for Hematology Annual Meeting 2018.
• December 2018: Newcastle University Faculty of Medical Sciences Travel Grant (£724.33). To fund attendance of the American Society for Hematology Annual Meeting 2018.
• September 2018: Newcastle Hospitals Charity Research Grant. One year duration (£49,260). In collaboration with Professor Christine Harrison. Project title: “Functional assessment of chromosome 21 candidate genes in precursor B-cell acute lymphoblastic leukaemia (B-ALL)”.
• March 2017: Newcastle University Post Graduate Cancer Conference. Best 3-minute thesis (£50 award).

Memberships

British Association for Cancer Research

European Association for Cancer Research

Manuscript Peer Review

Leukemia

Current research

Medulloblastoma (MB) is the most common malignant paediatric brain tumour. It is a biologically heterogeneous disease which is currently classified into four consensus molecular groups, MB_WNT, MB_SHH, MB_Group3 and MB_Group4, depending upon the genomic and epigenomic landscape of the tumour at diagnosis. Further substructure exists within these consensus molecular subgroups, and in addition MB tumours can be classified into four histological subtypes: classic (CLA), large cell and anaplastic (LCA), desmoplastic nodular (DN) and MB with extensive nodularity (MBEN). These histological subtypes are predominantly present across all molecular groups; however, the presence of specific cellular morphology/histology can be associated with a particular prognosis.

Recent improvements to genetic profiling, treatment stratification and biomarker discovery have led to increased patient survival; however, survival rates have currently stagnated at ~70%, with refractory tumours, tumour recurrence and long-term treatment-related side effects representing major clinical challenges in MB treatment.

My current research focuses on harnessing next generation sequencing techniques, contemporary bioinformatics, digital pathology, machine learning and artificial intelligence approaches to improve our understanding of MB tumour biology and ultimately lead to improved characterisation and disease classification of MB tumours, aid in the identification of disease biomarkers and help identify novel therapeutic targets for improved survival of children with medulloblastoma.

Previous research

My previous research has focused on two types of childhood leukaemia: B-cell precursor acute lymphoblastic leukaemia (B-ALL) and acute myeloid leukaemia (AML). My research has focused on the transcriptional profiling of iAMP21-ALL patients and the identification and characterisation of candidate oncogenes located on chromosome 21 within this subgroup using CRISPR-mediated gene editing approaches. In my AML research, I utilised the genomic and transcriptomic data from childhood AML patients enrolled in the MyeChild01 clinical trial to identify gene fusions and mutations, and analyse transcriptional profiles to enhance risk stratification in these patients.

Student supervision

1 PhD student (2024-current)

1 MRes student (2024-current)

1 MSci student (2020-current)

2 BSc students (2019-current)

Teaching

BGM1004: Genetics. Seminar host (2020-current)

• Articles

  • Ryan SL, Peden JF, Kingsbury Z, Schwab CJ, James T, Polonen P, Mijuskovic M, Becq J, Yim R, Cranston RE, Hedges DJ, Roberts KG, Mullighan CG, Vora A, Russell LJ, Bain R, Moorman AV, Bentley DR, Harrison CJ, Ross MT. Whole genome sequencing provides comprehensive genetic testing in childhood B-cell acute lymphoblastic leukaemia. Leukemia 2023, 37, 518-528.
  • Gao Q, Ryan SL, Iacobucci I, Ghate PS, Cranston RE, Schwab C, Elsayed AH, Shi L, Pounds S, Lei S, Baviskar P, Pei D, Cheng C, Bashton M, Sinclair P, Bentley DR, Ross MT, Kingsbury Z, James T, Roberts KG, Devidas M, Fan Y, Chen W, Chang T, Wu G, Carroll A, Heereema N, Valentine V, Valentine M, Yang W, Yang JJ, Moorman AV, Harrison CJ, Mullighan CG. The genomic landscape of acute lymphoblastic leukemia with intrachromosomal amplification of chromosome 21. Blood 2023, 142(8), 711-723.
  • Schwab C, Cranston RE, Ryan SL, Butler E, Winterman E, Hawking Z, Bashton M, Enshaei A, Russell LJ, Kingsbury Z, Peden JF, Barretta E, Murray J, Gibson J, Hinchliffe AC, Bain R, Vora A, Bentley DR, Ross MT, Moorman AV, Harrison CJ. Integrative genomic analysis of childhood acute lymphoblastic leukaemia lacking a genetic biomarker in the UKALL2003 clinical trial. Leukemia 2023, 37, 529-538.
  • Sinclair PB, Cranston RE, Raninga P, Cheng J, Hanna R, Hawking Z, Hair S, Ryan SL, Enshaei A, Nakjang S, Rand V, Blair HJ, Moorman AV, Heidenreich O, Harrison CJ. Disruption to the FOXO-PRDM1 axis resulting from deletions of chromosome 6 in acute lymphoblastic leukaemia. Leukemia 2023, 37, 636–649.
  • Schwab CJ, Murdy D, Butler E, Enshaei A, Winterman E, Cranston RE, Ryan S, Barretta E, Hawking Z, Murray J, Antony G, Vora A, Moorman AV, Harrison CJ. Genetic characterisation of childhood B-other-acute lymphoblastic leukaemia in UK patients by fluorescence in situ hybridisation and Multiplex Ligation-dependent Probe Amplification. British Journal of Haematology 2022, 196(3), 753-763.
  • Sinclair PB, Ryan S, Bashton M, Hollern S, Hanna R, Case M, Schwalbe EC, Schwab CJ, Cranston RE, Young BD, Irving JAE, Vora AJ, Moorman AV, Harrison CJ. SH2B3 inactivation through CN-LOH-12q is uniquely associated with B-cell precursor ALL with iAMP21 or other chromosome 21 gain. Leukemia 2019, 33, 1881-1894.

• Conference Proceedings (inc. Abstracts)

  • Cranston RE, Sinclair PB, Bashton M, Selby MP, Harrison CJ. A Genome-Wide CRISPR Screen Implicates MYC Dysregulation in TCF3-PBX1 B-ALL. In: 60th ASH Annual Meeting. 2018, San Diego, CA, USA: American Society of Hematology.
  • Selby MP, Finetti MA, Bashton M, Cranston RE, Del-Carpio-Pons A, Bailey S, Clifford SC, Williamson D. Investigating the biology of atypical teratoid/rhabdoid tumors by whole genome CRISPR/CAS9 screening. In: 17th International Symposium on Pediatric Neuro-Oncology (ISPNO). 2016, Liverpool: Oxford University Press.
  • Finetti MA, Selby MP, Pons AD, Wong JP, Bashton M, Cranston RE, Barker J, Crosier S, Smith A, Ramli RA, Grabovska Y, Bailey S, Huang PH, Clifford SC, Williamson D. Integrated pathway analysis of malignant rhabdoid tumour identifies key SMARCB1-pathways and therapeutic opportunities. In: 28 EORTC – NCI – AACR Symposium on Molecular Targets and Cancer Therapeutics. 2016, Munich, Germany: Elsevier.