Scientist

McMaster Stem Cell and Cancer Research Institute (SCC-RI)

Assistant Professor, Surgery, Division of Neurosurgery

Dr. Sheila Singh joined the McMaster Stem Cell and Cancer Research Institute in July 2007. Prior to her arrival at McMaster, Sheila completed a PhD at the Hospital for Sick Children. She obtained her degree within the Surgeon Scientist Training Program at the University of Toronto, where she completed her residency training specializing in pediatric neurosurgery.

Dr. Singh's research program is centred on the study of cancer stem cells. She recently identified an abnormal stem cell that may drive the formation of brain tumours. Using the cell surface protein CD133, Dr. Singh has characterized a rare subpopulation of brain tumour cells that exclusively generate a replica of the patient's tumour and exhibit self-renewal ability in vivo through serial retransplantation.

Her research program will focus on further molecular and genetic characterization of the brain tumour initiating cell (BTIC), and the molecular signalling pathways that are dysregulated in this cell to allow for brain tumorigenesis.

Research aims

• Characterization of the Heterogeneity of Human Brain Tumour Initiating Cells (BTICs)
  Building upon previously applied and refined cell culture techniques developed for the isolation of normal neural stem cells (NSC) to brain tumours, and development of a xenograft model to efficiently study BTIC activity, Dr. Singh's lab will further define novel candidate cell surface markers to enrich for cancer stem cells. Using fluorescent activated cell sorting for multiple markers and conducting prospective isolation of different classes of brain tumour stem cells and gene expression profiling of tumour stem cells compared to their non-self-renewing neighbours, could potentially lead to the development of a molecular signature for each brain tumour subtype that will provide the platform to target new chemotherapies.
• Comparative Analysis of Normal NSCs vs BTICs
  Mechanisms that govern self-renewal and multipotentiality in a normal NSC might be dysregulated to generate a brain tumour. Dr. Singh’s program aims to understand the molecular mechanisms of BTIC self-renewal in human brain cancers including adult glioblastoma and pediatric medulloblastoma. Using her xenograft model coupled with either transgenic overexpressing BTICs or siRNA knockdown, Dr. Singh's lab will respectively overexpress or underexpress key molecular mediators in the BTIC population permitting the functional characterization of signalling pathways that are disrupted during the possible transformation of a NSC to a BTIC.
• Development of Therapeutic Targets for Brain Tumours.
  The cancer stem cell hypothesis predicts that even if a tumour shows a substantial decrease in size in response to a therapy, if the cancer stem cells are spared, the tumour will regrow and the patient will have a clinical relapse. Capitalizing on approaches described in Research Aim 1 and 2 above, Dr. Singh will apply rapid prospective purification of the BTIC, using a host of new potential BTIC markers, which may allow clinicians to pinpoint the transformed cell within a lineage hierarchy, and target it with appropriately tailored drug and molecular therapies. A functional analysis of BTICs from individual patients using in vitro clonogenic assays and in vivo tranplantation assays may also provide a novel means for testing of new treatment strategies that focus on the eradication of the tumour-maintaining BTIC.

Education

2007 — F.R.C.S.(C)  Neurosurgery
2001-2005 — PhD, University of Toronto
1994-1997 — MD, McMaster University
1990-1994 — BSc, Honours Neurobiology, McGill University

Honours and Awards

Selected Publications

• C Venugopal, N McFarlane, SM Nolte, B Manoranjan, SK Singh. Processing of primary brain tumor tissue for stem cell assays and flow sorting. Journal of Visual Experimentation (JoVE) (In Press, November 2011).
• B Manoranjan, C Venugopal, SE Dunn, K Scheinemann, B Doble, SK Singh. Medulloblastoma Stem Cells. CANCER LETTERS (In Press, October 2011).
• B Manoranjan, C Venugopal, N McFarlane, B Doble, SE Dunn, K Scheinemann, SK Singh. Medulloblastoma stem cells: where development and cancer cross pathways. Pediatric Research (In Press, for April 2012).
• N Li, C Venugopal, X Wang, B Manoranjan, M Lenkiewicz, T Gunnarsson, R Hollenberg, P Klurfan, N Murty, C Wynder and SK Singh. Bmi1 marks intermediate precursors during differentiation of human brain tumor initiating cells. Stem Cell Research 2012: 8; pp 141–153.
• D Reddy, T Gunnarsson, K Scheinemann, JP Provias, SK Singh. Choroid Plexus Papilloma: A rare presentation with a novel surgical approach. Minimally Invasive Neurosurgery (In Press, August 2011).
• D Sommer, W Minet, SK Singh. Endoscopic Transnasal Drainage of Frontal Epidural Abscesses. Journal of Otolaryngology 2011: 40(5), pp401-406.
• A Fotovati, S Abu-Ali, PS Wang, C Lee, JY Chen, S Franciosi, J Triscott, Y Nakamura, Y Sugita, T Uchiumi, M Kuwamo, BR Leavitt, SK Singh, B Reynolds, A Jury, C Jones, CJ Pallen, SE Dunn. YB-1 is a key factor in normal brain development and contributes to gliomagenesis through the maintenance of neural stem cells. Cancer Research 2011: 71(16): 5569-78.
• Trauma Association of Canada National C-spine Working Group members (lead author Seen Chung, including SK Singh). National Pediatric Cervical Spine Evaluation Pathway: consensus guidelines. Journal of Trauma 2011: 70(4); pp 834-42.
• X Wang, C Venugopal, B Manoranjan, N McFarlane, E O’Farrell, S Nolte, C Hawkins, T Gunnarsson, R Hollenberg, J Kwiecien, and SK Singh. Sonic hedgehog directly regulates Bmi1 in human medulloblastoma brain tumour initiating cells. Oncogene 2011: AOP June 20, pp1-13).
• K Scheinemann, F Stan, SK Singh. Gliomatosis cerebri: a multifaceted disease. Pediatric Blood and Cancer 2010: 54(6); pp 856-857.
• I Kurnaz, SK Singh, L Klimaschewski, O Demir. From birth til death: neurogenesis, cell cycle and neurodegeneration. Anatomical Records 2009: 292(12):1953-61.
• M Lenkiewicz, N Li and SK Singh. Culture and Isolation of Brain Tumor Initiating Cells. Current Protocols in Stem Cell Biology 2009, Chapter 3:Unit3 3.
• J Pasternak, M Fulford, J Provias, T Gunnarsson, SK Singh. An Unexpected Intracranial Pressure Crisis: Infant Brain Abscess of Unusual Etiology. Childs’ Nervous System, 2009: 25(3); pp 377-81.
• M Kohandel, SK Singh, S Sivaloganathanan. Characterization of Brain Cancer Stem Cells: A Mathematical Approach. Cell Proliferation, 2009: 42(4); pp 529-40.
• SK Singh, ID Clarke and PB Dirks. Cancer stem cells and CNS tumours. Neurosurgery Clinics of North America 2007: 18(1): pp31-38.
• Report and Citation of above paper (ref 10) in Nature News and Views: At the root of brain cancer. Nature 2004: Clarke, M: 7015(432): pp 281-282.
• SK Singh, C Hawkins, ID Clarke, J Bayani, J Squire, T Hide, RM Henkelman, MD Cusimano, PB Dirks. Identification of human brain tumour initiating cells. Nature 2004: 7015(432): pp 396-401.
• SK Singh, ID Clarke, T Hide, PB Dirks. Cancer Stem Cells in Nervous System Tumours. Oncogene 2004: 23; pp7267-7273.
• Report and Citation of above paper (ref 5) in Nature Reviews Cancer: Applying the principles of stem cell biology to cancer. Nature Reviews Cancer 2003: Pardal R, Clarke MF, Morrison SJ: 3: pp 895-902.
• Report and Citation of above paper (ref 5) in Science News Focus: Mutant Stem Cells may seed Cancer. Science 2003: Marx, J: 301(5638): pp 1308-1310.
• SK Singh, ID Clarke, M Terasaki, VE Bonn, C Hawkins, J Squire and PB Dirks: Isolation of a Cancer Stem Cell from Human Brain Tumours. Cancer Research 2003: 63(18): pp 521-528.