Muscle Gene Expression

Immunofluorescent image of a section of human skeletal muscle: fast twitch fibres are in red, slow twitch fibres are in green

We are interested in the mechanisms that govern control of cell phenotype. Our main focus is on the mechanisms by which activity regulates muscle phenotype in venous smooth muscle and in skeletal muscle. Our smooth muscle studies are investigating the role of the transcription factor KLF5 in the development of intimal hyperplasia following bypass grafting. We are now looking at methods of inhibiting KLF5 expression and activity with a view to developing interventions to inhibit intimal hyperplasia.

In collaboration with the muscle lab at the Royal Brompton Hospital we are investigating the mechanisms that contribute to the loss of muscle mass in patients with COPD. Within these studies we are investigating the role of the four and a half LIM domain (FHL) family of adapter proteins in regulating skeletal muscle fibre type and muscle mass. This analysis has shown that FHL1 is regulated by activity in COPD patients and likely to contribute to the fibre-type shift seen in these patients. We have also recently found that activity regulates the expression of myostatin in patients with COPD.

Selected publications

Amirak E; Zakkar M; Evans PC; Kemp PR. (1 Jan 2010). Perfusion of veins at arterial pressure increases the expression of KLF5 and cell cycle genes in smooth muscle cells. BIOCHEM BIOPH RES COMMUN. 391:818-823.

Gordon AR; Outram SV; Keramatipour M; Goddard CA; Colledge WH; Metcalfe JC; Hager-Theodorides AL; Crompton T; et al. (2 May 2008). Splenomegaly and modified erythropoiesis in KLF13(-/-) mice. J BIOL CHEM. 283:11897-11904.

Favot L; Hall SM; Haworth SG; Kemp PR. (Dec 2005). Cytoplasmic YY1 is associated with increased smooth muscle-specific gene expression - Implications for neonatal pulmonary hypertension. AM J PATHOL. 167:1497-1509.