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DAVID
MORROW, B.Sc.
Postgraduate
Research Student
- 2001-date:
Postgraduate Research Student, School of Biotechnology, Dublin
City University.
- 1997-2001:
B.Sc. in Cell and Molecular Biology, Faculty of Science, University
College Dublin.
Ongoing
Research
- Role
of the Notch receptor ligand-signaling pathway in determining vascular
smooth muscle cell proliferation in response to mechanical stimulation
Vascular
smooth muscle cell fate decisions, (proliferation, migration, differentiation
and apoptosis), play an important role in neointimal formation during
the pathogenesis of hypertension, intimal hyperplasia, atherosclerosis
and the arterial response to injury. Vascular cell fate decisions
are hallmarks of the response of phenotypically distinct vascular
smooth muscle cells to hemodynamic forces following injury. Since
these cell fate decisions are also apparent during vascular remodeling
of the embryonic vasculature, albeit in response to a different stimulus,
and since intimal cells resemble the immature 'pup' cells during embryogenesis,
we propose that control of these cell fate decisions following injury
may share a similar 'arbiter', namely the Notch receptor-ligand signaling
pathway.
Notch
receptor-ligand interactions are a highly conserved mechanism, originally
described in developmental studies using Drosophila, that regulate intercell
communication and direct individual cell fate decisions. Using a novel
perfused transcapillary co-culture in conjunction with the Flexercell®
Tension Plus™ FX-4000T™ system to subject vascular cells to pressure
and cyclic strain, we propose to evaluate the role of the Notch receptor
ligand-signaling pathway in determining vascular smooth muscle cell
proliferation in response to mechanical stimulation following injury.
Specifically, we propose to;
-
(i)
determine Notch receptor/ligand expression and signaling in vascular
smooth muscle cells following pressure-induced vascular proliferation
in vitro
-
(ii)
to determine the role of Notch receptor/ligand expression and signaling
in mediating pressure induced vascular smooth muscle proliferation
in vitro
-
(iii)
to determine the role of vascular smooth muscle cell phenotype in
dictating Notch receptor/ligand induced vascular smooth muscle proliferation
in vitro.
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