Vascular smooth muscle (VSM) cells under healthy conditions have a quiescent non-proliferative phenotype. However, VSM cell proliferation is the hallmark of cardiovascular disease. What drives VSM cell phenotypic switch from a contractile to a proliferative cell is as yet not know.  The hyperproliferative VSM cell can be further characterised by changes bioenergetics, an apoptotic resistant state and change in miRNA expression related to the aberrant disease phenotype.

Micro-vesicles are known to transport mRNA, miRNA, and proteins between cells in health and disease. A growing interest has focused on the role of exosomal trafficking in cancer a disease similarly characterised by a cell phenotype switch to hyperproliferation and increased migration.

This project will focus on profiling exosomal trafficking in VSM cells where the phenotypic status is manipulated (quiescent vs. proliferative). Further work will look at this phenotype manipulation in genetically modified mitochondrial incompetent cells to identify a role for mitochondria as a potential driver of the phenotype switching and cell-signalling mechanisms related to cardiovascular disease.  

Project Aim: Investigate the roll of mitochondrial-dependent cell signalling and exosomal trafficking

Laboratory based methods employed include cell and tissue culture. Cell transfection with siRNA, western blotting, QC-PCR, ELISA coupled with histology, immunohistochemistry and light and fluorescent microscopy.

1.      C Braicu, C Tomuleasa, P Monroig, A Cucuianu, I Berindan-Neagoe, and GA Calin. Exosomes as divine messengers: are they the Hermes of modern molecular oncology? Nature; Cell Death and Differentiation. 2015: 22; 34-45

2.      Al Sulti Z, McDonald R, Kingsmore D, Baker A, Coats P. Mitochondrial regulation of micro RNA synthesis in vascular smooth muscle cell proliferation Heart 2014; 100: 12-15

3.      Al-Sulti Z, Kingsmore D, Coats P. Mitochondrial-dependent signalling in vascular smooth muscle cell Proliferation. Heart. 2014; 100: 97