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Transcript
Dr. Sheila Singh’s Laboratory
Research Overview
Lab overview
• Operating since August 2007
• Located at the Stem Cell &
Cancer Research Institute at
McMaster Main Campus
• 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
Cancer Stem Cell Hypothesis & the BTIC
•
•
•
•
•
•
Nature. 2004;432(7015):281-2
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
Tumor spheres of Anaplastic medulloblastoma in vitro
100x
200x
0.05mm
400x
0.05mm
0.05mm
Tumor spheres of Metastatic Melanoma in vitro
200x
100x
0.05mm
200x
0.05mm
0.05mm
Day 7 Differentiated BTICs
Undifferentiated spheres
BTIC Differentiation