Assistant Professor of Molecular Neuro-Oncology, Faculty of Medicine & Health Sciences
After graduating with a BSc in Genetics at the University of Edinburgh, I completed a PhD in Molecular Biology at the Roslin Institute, Edinburgh under the supervision of Sir Ian Wilmut in 2007. I joined Professor Richard Grundy's laboratory at the Children's Brain Tumour Research Centre, University of Nottingham as a Post-Doctoral Research Associate in 2007 and received the Nottingham Advanced Research Fellowship for the Faculty of Medicine in 2011. I am currently an Assistant Professor of Molecular Neuro-Oncology at the University of Nottingham and lead research programmes in intracranial drug delivery, 3D brain tumour models and tumour heterogeneity. I also act as Deputy Chair for an international Children's Brain Tumour Drug Delivery Consortium which includes a 17-member steering committee spanning leading institutions across Europe and North America (Johns Hopkins University, National Cancer Institute).
Molecular and cellular neuro-oncology; biomaterial-based drug delivery.
Lecturing - 12 lectures (1 PhD, 7 BSc, 4MSc) across 7 modules.
University of Nottingham:
- Neuro-Oncological Application of Tissue Engineering Concepts - Tissue Engineering Course - CDT Regen Med (2017-present).
- Brain Cancer Future Medicines Seminar - BSc Biochemistry and Molecular Medicine, Year 3 Advanced Biochemistry of Cancer module (2016-present).
- Cancer Chemotherapy - Pre-Clinical/Clinical (BSc Biochemistry and Molecular Medicine, Year 3 Advanced Biochemistry of Cancer module (2015-present).
- Cancer Evolution I: Principles (BSc Biochemistry of Cancer C74CAN, Year 3 Advanced Biochemistry of Cancer module (2016-present).
- Cancer Evolution II: Application (BSc Biochemistry of Cancer C74CAN, Year 3 Advanced Biochemistry of Cancer module (2015-present).
- Biology of Metastasis - Adhesion Molecules and Cell-Cell/Matrix Interactions 1 (Migration) (MSc Oncology, A34C02/L/05 Tumour Physiology) (2015-present).
- Biology of Metastasis - Adhesion Molecules and Cell-Cell/Matrix Interactions 2 (Invasion) (MSc Oncology, A34C02/L/05 Tumour Physiology) (2015-present).
- Tumours of the Brain (BSc Graduate Entry Medicine BMBS) (2015 - present).
- Biomaterials and Cancer Therapeutics (BSc Medical Physiology and Therapeutics - 3rd Year Cancer Biology Module) (2014 - present). (Setting, marking and moderating MCQ/SAQ for ~35 students).
- Localised drug delivery for brain cancer (BSc Medical Physiology and Therapeutics - 3rd Year Cancer Biology Module) (2014 - present).
- Leukaemic Stem Cells (MSc. Stem Cell Technology) (2012-present).
Keele Medical School:
- Stem Cells in Cancer (MSc. 'Cell and Tissue Engineering' (2007-present).
My research group are broadly interested in two research themes: 1) Molecular Neuro-Oncology; 2) Brain tumour drug delivery.
1) Molecular Neuro-Oncology:
We have established dynaimc 3D brain tumour culture models using the NASA-developed Rotary Cell Culture System (RCCS). The molecular biology and genetics of brain tumour cells grown as 3D cultures better resembles the biology of the patients' tumour, when compared to traditional 2D cultures. We are now using this culture system to test the effectiveness of novel candidate anti-cancer drugs, thus avoiding the requirement to test such drugs in animals in the first instance.
We are also aiming to identify whether the biology of a brain tumour called glioblastoma (GBM), varies in different regions within each tumour (intratumour heterogeneity). Through a precise reading of the information carried in GBM DNA, we will spot 'errors' (mutations) that enable the cancer to survive. Similarly, by reading the information carried in GBM RNA, we will identify genes incorrectly switched on. A key goal will be to combine data on mutations and genes from different parts of the tumour to reveal which mutations are crucial to its survival. If these genes are identified, the proteins involved will also be known. Drugs that target these proteins will be tested on GBM cells grown in the RCCS and in mice with GBM tumours.
To complement our genome wide genetic mutation and gene expression analyses, my group is also developing a functional genomics approach to study GBM intra-tumour heterogeneity. Specifically we are conducting phospho-proteomics and metabolomics using advanced mass spectrometry methods.
2) Brain tumour drug delivery:
Current methods to deliver cancer chemotherapy drugs results in drugs reaching all parts of the body, causing the death of healthy cells. This also means that the amount of drug that reaches the tumour may not be enough to destroy it. We have evaluated a new drug delivery system which uses polymer microparticles to deliver drugs directly to the site of the tumour at the time of surgery, thereby targeting cancer cells that are often left behind and reducing drug-related side-effects throughout the body.The opportunity to deliver cancer drugs locally within the tumour resection cavity bypasses the blood-brain-barrier, targeting micro-deposits of neoplastic cells that remain following tumour resection. This has the potential to achieve a high effective dose locally whilst maintaining a low toxic dose systemically.
British Neuro-Oncology Society Conference - Best Oral Presentation Jul 2015 (1st).
School of Medicine Clinical Showcase - Best Poster Prize, Apr 2015 (1st).
British Neuro-Oncology Society Young Investigator Award 2014 (* Highest national accolade in the field of neuro-oncology for basic or clinical scientists under the age of 35).http://blogs.nottingham.ac.uk/pressoffice/2014/07/09/national-award-for-innovative-nottinghamresearcher/
Genetics Society international writing competition, 2004 (1st) (Rahman R. "The Stems of Cancer".Genetics Society Newsletter 2005; (52) 50-52).
Society for Neuro-Oncology (San Antonio, 20/11/2015) - Delineating intra-tumour metabolomic and phospho-proteomic heterogeneity in glioblastomas through advanced analytical methods.
Departments of Oncology and Stem Cell Research - (Imperial College London, 27/11/14). (Seminar) Glioma heterogeneity: from modeling to therapy.
British Neuro-Oncology Society (University of Liverpool, 03/07/2014) - Title: Glioma heterogeneity: from modeling to therapy. * Young Investigator Award Prize Lecture.
Society for Neuro-Oncology Basic and Translational Research (Fort Lauderdale, 16/05/2013) - Session: High Grade Glioma; Title: VEGF/FGF-dependent vasculogenic mimicry and tumor-derived angiogenic response in high grade glioma.
International Symposia for Pediatric Neuro-Oncology (Toronto, 26/06/2012) - Session: Advances in Neurosurgery; Title: Adjuvant chemotherapy for brain tumors delivered via a novel intra-cavity moldable polymer matrix.
Society for Neuro-Oncology Basic and Translational Research (New Orleans, 19/05/2011) - Session: High Grade Glioma and Ependymoma; Title: Evaluating novel polymeric microparticle-based injectable matrices for local chemotherapeutic delivery.
British Neuro-Oncology Society (University of Cambridge, 01/07/2011) - Title: Evaluating novel polymeric microparticle-based injectable matrices for local chemotherapeutic delivery.
I have studied the role of the telomere and telomerase pathways with respect to childhood brain cancer progression, particularly with respect to targeting telomerase as a potential mode of therapy. I have investigated the role of histone deacetylase inhibition using Trichostatin A in high grade paediatric tumours and have shown distinct telomerase inhibition associated with anti-proliferative and pro-apoptotic cellular effects. Additionally, I have evaluated the role of the G4 quadruplex ligand, RHPS4 in indirectly inhibiting telomerase by restricting access to the telomere. I am also interested in determining the contribution of dysregulated stem-like cells to childhood brain tumours and understanding mechanisms of resistance such cells may harbour; e.g.- cellular quiescence.
Functional Genomic Characterisation of Intra-glioma Heterogeneity
To complement our genome wide genetic mutation and gene expression analyses, my group is also developing a functional genomics approach to study GBM intra-tumour heterogeneity. Specifically we are conducting phospho-proteomics and metabolomics using advanced mass spectrometry methods. We hypothesise that active proteins and metabolites predominant at the glioma invasive margin, represent clinically-relevant targets for therapy. We will develop orthotopic patient-derived xenografts using cells isolated from the invasive margin, thus representing a pre-clinical tailored pharmacological framework.
3D Cell Culture Models of Brain Tumours
We aim to assess whether these models are able to predict drug response in animals and in patients receiving identical therapy and use this system to test the anti-cancer effects of a new group of drugs called histone deacetylase inhibitors.
Local Drug Delivery for Brain Tumours
We aim to evaluate efficacy and neurotoxicity of our polymer-based drug delivery system in vivo. Additionally we will further develop the biomaterials approach to demonstrate greater flexibility in tailoring drug release profiles.