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Our work focuses on
four main themes:
How is size
controlled? Organs and organisms grow to reproducible sizes, but very
little is known on how an organ "knows" what size it is, to
consistently control tissue growth. Work in our lab is exploring how Drosophila tumour
suppressor gene, called fat,
regulates the growth of cells in tissues. Fat is an extremely
large (560 kDa) cell adhesion molecule.
Loss of Fat yields tissues that are up to 8 times larger than wildtype controls-yet at present, little is known about
how Fat restricts growth.
How do cells become
assembled into complex, beautifully organized tissues?
Intriguingly, Fat also controls a high-level form of tissue patterning,
called planar polarity. We want to understand the signal transduction
pathway by which this large adhesion molecule regulate
tissue organization. we also want to
understand if the control of growth and patterning by Fat are linked.
We have conducted molecular and genetic screens for elements of the Fat
pathway in Drosophila, and are currently dissection the biochemical pathway of Fat
signaling. In addition, we have recently identified a human homolog
of Fat, ad are exploring if Fat regulates proliferation and planar polarity
in mammals.
How
do cells develop cellular polarity? A serine-threonine
kinase, called LKB1 regulates cell polarity in C. elegans, Drosophila,
and man. Mutations in LKB1 lead to an increased risk of cancer, suggesting
that the control of cell polarity may be important to cancer. We are
using genetics and biochemistry in Drosophila
to understand how this conserved kinase controls
cell polarity.
How is the timing
of differentiation controlled? Multicellular
organisms must integrate growth and differentiation precisely to pattern
complex tissues. Despite great progress in understanding how
different cell fates are induced, it is poorly understood how
differentiation decisions are temporally regulated. We have recently
found that pathways previously shown to regulate cell growth and
proliferation have an important role in controlling the timing of
differentiation. We are exploring how these pathways regulate
differentiation, using molecular and genetic screens in tissue culture
models and in Drosophila.
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