Postgraduate Research Student
- 2001-date: Postgraduate Research Student, School of Biotechnology, Dublin City University.
- 1995-2000: M.Sc. in Biotechnology, Adam Mickiewicz University, Poznan, Poland.
Ongoing Research
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Role of the Notch receptor ligand-signaling pathway in controlling vascular smooth muscle cell differentiation in response to mechanical stimulation
Our overall hypothesis is that Notch receptor ligand signaling dictates, in part, vascular smooth muscle cell (VSMC) fate in response to mechanical stimuli. Vascular differentiation is one such cell fate decision that has important implications for vascular development and remodeling. Unlike skeletal muscle fibers and cardiac myocytes, VSMCs display remarkable plasticity in terms of differentiation, proliferation, and motility, characteristics that are particularly evident when adult arteries undergo an orchestrated remodeling process. Using a novel perfused transcapillary culture system, we have previously shown that pulse-pressure induces the growth and migration of vascular smooth muscle cells in vitro. Moreover, the differentiation state (phenotype) of these cells dictates their underlying response to changes in mechanical load. VSMCs recapitulate some aspects of ontogenesis when hyperplastic or hypertrophic growth is induced in adulthood as part of an adaptive response to an increased mechanical load. Thus, delineation of the mechanisms controlling the differentiation state of VSMCs is of critical importance in determining the cell fate response of these cells to mechanical stimulation.
My project focusses on the role of Notch receptor ligand signaling in controlling VSMC differentiation and and its role in mechanical force-induced changes in vascular structure. Specifically, using a novel in vitro perfused transcapillary culture system in conjunction with vascular smooth muscle cells stretched in a coordinated fashion using the Flexercell® Tension Plus™ FX-4000T™ system, we propose to;
(i) determine Notch receptor/ligand expression and signaling in vascular smooth muscle cells following pressure-induced vascular differentiation in vitro
(ii) to determine the role of Notch receptor/ligand expression and signaling in mediating pressure induced vascular smooth muscle differentiation in vitro
(iii) to determine the role of vascular smooth muscle cell phenotype in dictating Notch receptor/ligand induced vascular smooth muscle differentiation in vitro following exposure to pressure and cyclic strain.
The central objective is to explore the role of a novel developmental signaling pathway for controlling vascular cell fate decisions following a physiologically relevant stimulus. This research will provide valuable new information central to our understanding of the potential novel role for the Notch signaling pathway in vascular remodeling, and thus further our knowledge of the critical role of hemodynamic forces in the biology of vascular cell function and behavior.
