Contact
Teaching Summary
Lecturer - Keele Medical School: 'Stem Cells in Cancer' (MSc 'Cell and Tissue Engineering', 2007-present.
Co-supervisor PhD student (2009-present)
Primary supervisor for Biomedical Sciences Hons. Students (2007-2010)
Primary supervisor for Biochemistry Honours Student (2010).
Co-supervisor for MSc. 'Stem Cell Technology' student (2010).
Research Summary
Local Drug Delivery for Brain Tumours
Central nervous system tumours are the major cause of cancer related death in children. 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.
3D Cell Culture Models of Brain Tumours
Despite many new drugs showing therapeutic potential in laboratory-based studies, the majority are ineffective in animals and/or in patients. One reason for this discrepancy is the lack of reliable brain cancer models in the laboratory. We have developed 3D childhood brain tumour models using the Rotary Cell Culture System (RCCS), whereby 0.2-0.8 cm3 aggregates are generated by maintaining cells in suspended culture. One to three week tumour aggregates recapitulate many key pathophysiological characteristics of primary paediatric brain tumours: proliferating, senescent and necrotic regions; heterogeneous aggregates of brain tumour cells/human brain endothelial cells (HBMEC) displaying enriched vessel-like structures expressing vessel wall markers; slower growth rate; upregulation of angiogenesis; differential expression of extracellular matrix genes; distinct microRNA clustering and different metabolic profiles.
Recent Publications
RIDLEY, LEE, RAHMAN, RUMAN, BRUNDLER, MARIE-ANNE, ELLISON, DAVID, LOWE, JAMES, ROBSON, KEITH, PREBBLE, EMMA, LUCKETT, INGA, GILBERTSON, RICHARD J, PARKES, SHEILA, RAND, VIKKI, COYLE, BETH and GRUNDY, RIC, 2008. Multifactorial analysis of predictors of outcome in pediatric intracranial ependymoma. Neuro-oncology. 10(5), 675-89 RAHMAN, RUMAN, FORSYTH, NICHOLAS R and CUI, WEI, 2008. Telomeric 3'-overhang length is associated with the size of telomeres. Experimental Gerontology. 43(4), 258-65
PRIMARY ARTICLES AND REVIEWS
Tan T, Rahman R, Jaber Hijazi F, Felix D, Chen C, Louis E, and Aboobaker A. Telomerase activity in adult stem cells is adapted to an immortal life history in obligate asexual worms. Submitted to Proceedings of the National Academy of Sciences USA.
Rahman R & Grundy R. Histone deacetylase inhibition as an anti-telomerase targeting strategy. International Journal of Cancer (2011) 129: 2765-2774.
Hussein D, Punjaruk W, Storer L, Shaw L, Ottoman R, Peet A, Miller ...Rahman R......Coyle B. Pediatric brain tumour cancer stem cells: cell cycle dynamics, DNA repair, and etoposide extrusion. Neuro-oncology (2011) 13: 70-83.
Rahman R, Osteso-Ibanez T, Hirst R, Levesley J, Quinn S, O'Callaghan C, Coyle B, Grundy R. Histone deacetylase inhibition attenuates cell growth with associated telomerase inhibition in high grade paediatric brain tumour cells. Molecular Cancer Therapeutics (2010) 9: 2568-2581.
Rahman R, Smith S, Rahman C, Grundy R. Anti-angiogenic therapy and mechanisms of tumour resistance in malignant glioma. Journal of Oncology (2010) 2010:251231
Rahman R, Kilday J-P, Ridley L, Lowe J, Rand V, Grundy R. Pediatric ependymoma: Biological perspectives. Molecular Cancer Research (2009) 7(6):765-786.
Rahman R, Heath R, Grundy R. Cellular immortality in brain tumours: An integration of the cancer stem cell paradigm. Biochimica et Biophysica Acta - Molecular Basis of Disease (2009) 1792: 280-288
Rahman R, Ridley L, Brundler M-A et al. Multifactorial analysis of predictors of outcome in pediatric intracranial ependymoma. Neuro-oncology (2008) 10: 675-689
Rahman R, Forsythe N, Cui W. Telomeric 3'-overhang length is associated with the size of telomeres. Experimental Gerontology (2008) 43: 258-65.
Rahman R, Mo L, Cui W. Telomerase with mutated catalytic motifs has dominant negative effects on telomerase activity and inhibits cell growth. Biochemical and Biophysical Research Communications (2006) 350: 796-802.
BOOK CHAPTERS
Rahman R. Histone deacetylase inhibitors as an anti-cancer telomerase targeting strategy. 'Telomerase: Composition, Functions and Clinical Implications' Chapter 3 p59-79 (2010) (Nova publishing).
Rahman R & Grundy R. Cellular immortality in brain tumours: An overview. Tumors of the Central Nervous System, Volume 3, Chapter 3 (2011) (Springer).
CONFERENCE PROCEEDINGS
Rahman R, Rahman C, Smith S, MacArthur D, Rose F, Shakesheff K, Grundy R. Evaluating novel polymeric microparticle-based injectable matrices for local chemotherapeutic delivery. Neuro-Oncology (2011), Volume 13, Supplement 1; ISSN 1522-8517 (Print); ISSN 1523-5866 (Online).
Rahman R, Smith S, Rahman C, MacArthur D, Rose F, Shakesheff K, Grundy R. Increased expression of angiogenic genes: vasculogenic mimicry in a three-dimensional culture system. Neuro-Oncology (2011), Volume 13, Supplement 1; ISSN 1522-8517 (Print); ISSN 1523-5866 (Online).
Rahman R, Osteso-Ibanez, Hirst RA, Quinn, S, Coyle B, O'Callaghan C, Grundy R. Histone deacetylase inhibition attenuates cell growth with associated telomerase inhibition in high grade paediatric brain tumour cells. 14th International Symposium on Pediatric Neuro-Oncology, 20-23 June 2010, Vienna, Austria. Neuro-oncology 2010 12: ii87; doi:10.1093/neuonc/noq043.
Rahman R, Ridley L. Quinn S, Coyle B, Grundy R. Contrasting telomere dynamics between neuronal and glial paediatric brain tumours. (ISPNO - Chicago, 2008). Neuro-oncology 10(3):376