1. Dr. Sheila Singh’s Laboratory Lab overview Operating since August 2007 Located at the Stem Cell & Cancer Research Institute at McMaster Main Campus Research Overview Dr. Singh is a pediatric neurosurgeon and scientist This is a basic science laboratory with a strong clinical focus The overall research goal is to further elucidate the cancer stem cell hypothesis in brain tumours and to characterize the Brain Tumour Initiating Cell (BTIC) Our work includes tissue culture, molecular biology experiments and in vivo animal work

2. Cancer Stem Cell Hypothesis & the BTIC Neural stem cells (found in brain) are tightly regulated & differentiate into normal cells of brain tissue Cancer neural stem cells, by virtue of mutations, are dysregulated, & self renew & differentiate aberrantly, generating the abnormal cells that make up the brain cancer The BTIC was identified by its cell surface protein expression of CD133 In 2004, Singh et. al identified an abnormal stem cell (termed the BTIC) that drove the formation of brain tumours (Nature, 2004;432(7015):396-401) BTIC’s represent a small fraction of the whole tumour, but these cells alone may be entirely responsible for the continued growth of the tumour Clinical implications: therapies that focus on killing the bulk of the tumour may miss the rare stem cell fraction, allowing the tumour to continue to grow & potentially metastasize to form secondary tumours Nature. 2004;432(7015):281-2

3. 200x 0.05mm 200x 0.05mm Tumor spheres of Anaplastic medulloblastoma in vitro 100x200x400x 0.05mm Tumor spheres of Metastatic Melanoma in vitro 100x 0.05mm

4. Undifferentiated spheres Day 7 Differentiated BTICs BTIC Differentiation