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Current
Laboratory Members |
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Research
Interests - Overview |
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My research
group has three main areas of interest: (i) regulation of gene
expression during retinal development (see Project Details – Project
1), (ii) characterization of a DEAD box protein called DDX1 in the
human tumour of the retina called retinoblastoma (Project 2), and
(iii) induction of differentiation in brain tumours (Project 3)
Projects 1 and 2: Retinoblastoma, a childhood tumour of the eye,
occurs when both copies of the retinoblastoma (RB) gene are mutated
in retinal precursor cells. In spite of extensive investigations of
the RB gene, no one truly understands how retinal precursor cells
become tumorigenic. We are using different approaches spanning the
fields of molecular biology, cellular biology and developmental
biology, to study the spectrum of changes in retinal cells compared
to retinoblastoma tumour cells.
Project 3: Malignant gliomas are deadly brain tumours that are
extremely aggressive and hard to treat. We believe that malignant
glioma tumours are derived from a glial cell that is normally highly
invasive during brain development. We propose that a better
understanding of the genes expressed in normal glial cells will shed
light on how to control the aggressive properties of brain tumours.
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Ongoing Research
Highlights |
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Identification of a
transcription factor that is specifically expressed in
two types of neuronal cells in the developing retina: amacrine and horizontal
Discovery of a novel member of the DEAD box protein
family called DDX1 that is over-expressed in childhood
tumours
Identification and characterization of a novel
alternatively spliced form of Disabled-1 (Dab-1)
expressed in retinal precursor cells
Discovery of a new type of nuclear body called ‘DDX1
foci’ found in a wide variety of cell types
Finding that a glial cell marker called brain fatty
acid-binding protein (B-FABP) is expressed in malignant
glioma tumours
Identification of genes that are asymmetrically
expressed at early stages of retinal development |
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Selected
Trainee Publications |
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Sachin Katyal :
Ph.D. Student
In this paper,
Sachin identifies a novel form of the Disabled-1
(Dab1) gene that is specifically expressed in the
undifferentiated cells of the developing retina. He
characterizes the function of this novel form of
Dab1 and identifies regions within the Dab1 protein
that are critical for relaying extracellular
signals, through modulation of protein phosphorylation. |
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Lei Li : Ph.D.
Mol. Cell. Biol.
In this paper,
we study the role of the putative RNA helicase, DEAD
box 1 (DDX1), in cells treated with ionizing
radiation. We report that DDX1 protein is rapidly
recruited to sites of DNA double-strand breaks where
it co-localizes with g-H2AX and phosphorylated ATM.
DDX1 function appears to be mediated through
phosphorylation by ATM. Our data suggest that DDX1
unwinds RNA-DNA hybrid molecules at sites of DNA
double-strand breaks and likely plays a role in the
clearance of RNA to facilitate repair of DNA.
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