Science of stem cells

Satellite cell on muscle fibreSatellite cell on muscle fibreOur fundamental research aims to identify and manipulate the genes that regulate self-renewal, migratory ability, survival and in vivo differentiation of cells that could potentially be used to treat disease.

We are also evaluating how modifications in cultivation procedures affect stem cell behaviour. It is crucial to understand these effects if we are to develop safe, reproducible regenerative therapies in the future.

Our focus is on stem cells of the skeletal muscle and epithelia.



Skeletal muscle

We will use fundamental research on stem cells in skeletal muscle to inform pre-clinical work and clinical trials focused on Duchenne muscular dystrophy (DMD). DMD results from a mutation in the cytoskeletal protein dystrophin.

Human mesoangioblastsHuman mesoangioblastsSome key areas of our work are:

1. Factors that control the fate choices of myogenic stem cells

Our studies cover genetic, epigenetic and environmental factors that influence self-renewal, differentiation and regenerative capacity. We consider satellite cells, mesoangioblasts and CD133+ cells in this context. CD133+ cells are human stem cells isolated from patients’ blood and skeletal muscle, then engineered to produce functional dystrophin.

 

2. Methods for extending the proliferative lifespan of myogenic stem cells without affecting differentiation potential

We are attempting to extend cell lifespan by: (a) modification of myogenic cells using inducible genes; (b) identification of new culture conditions and growth media.

 

 

Epithelia

Our epithelial research focuses on the behaviour of stem cells in skin, ocular, oral and thymic epithelia. These studies will inform pre-clinical work and clinical trials focused on severe damage to the epidermis, ocular surface or oral mucosa.

Some key areas of our work are:
1. Molecular phenotypes of epithelial stem cells and the genetic programs underlying their properties

We are studying human epidermal, limbal-corneal, conjunctival, oral, urothelial and thymic stem cells with a view to identifying molecular phenotypes and the systems governing cell fate. We are developing transcriptome maps for stratified epithelia, and will use these to discover whether trans-differentiation is possible.

 

2. Molecular characteristics of epidermal stem cells and the pathways responsible for self-renewal

We aim to uncover: (a) the signaling molecules involved in the reconstruction of the stem cell niche when donor cells are engrafted; (b) why epidermal appendages, such as hair follicles and sweat glands, do not regenerate in human cultured skin grafts.

 

3. Differentiation of corneal stem cells and plasticity of oral mucosal stem cells

We are investigating: (a) the molecular switch that gives rise to conjunctival stem cell derived goblet cells; (b) the plasticity of oral mucosal stem cells. We hope that oral mucosal stem cells may be able to regenerate the corneal epithelium in cases of complete corneal destruction.