- The role of TGF-beta superfamily signalling in cardiovascular and pulmonary development and disease
- The mechanism underlying mammalian pluripotency and direct nuclear programming
- The translation of pluripotent stem and progenitor cells for viable cell and gene therapies.
Our lab’s interests are concerned with understanding the cellular and genetic mechanisms that underlie cell-fate decisions during (a) the embryogenesis, maintenance and repair/regeneration of the cardiovascular and pulmonary systems and (b) direct nuclear programming of somatic cells to pluripotency and cardiovascular/pulmonary fates.
The knowledge gained from this understanding is being used to bring cellular and gene therapies to the translational phase for drug development, tissue regeneration and replacement and gene corrections/enhancements in vivo. We are also working to better understand the different states of pluripotency in mammals.
The role of TGF-beta superfamily signalling in cardiovascular and pulmonary development and disease
Elucidation of genetic networks underlying the embryogenesis, maintenance and repair/regeneration of the cardiovascular and pulmonary systems
The genetic networks that underlie the embryogenesis of the cardiovascular and pulmonary systems remain active during the processes of their maintenance and repair/regeneration. By studying the normal embryogenesis of these systems and applying the knowledge gained to the in vitro 3D modelling of them we hope to better understand human disease states affecting the cardiovascular and pulmonary systems. In these modelling studies we use genetically labelled differentiated cells, progenitor cells and/or pluripotent stem cells (ES cells and iPSCs, see below) or combinations thereof.
We have a particular focus on modelling Pulmonary Arterial Hypertension in collaboration with Professor Nick Morrell’s group and studying the role of TGF-beta superfamily signalling in endothelial, smooth muscle and cardiac cells. But we also have interests in other disease states such as Fibrodysplasia Ossificans Progressiva (FOP)
Our goals are to then use our 3D models in drug and toxicology screens for the development of drugs tailored to individual patients.
The nature of mammalian pluripotency and the translation of pluripotent stem and progenitor cells for viable cell and gene therapies
Direct nuclear programming of somatic cells to pluripotency and cardiovascular/pulmonary fates.
Induced pluripotent cells offer a powerful technology that will revolutionise the field of medicine, allowing us to generate patient specific pluripotent stem cells, which can be used for tailored drug discovery and toxicology screens and to regenerate and replace lost, damaged or dysfunctional tissue.
However, to progress iPSC technology to the translational phase we need to improve (i) the practicalities of obtaining bankable patient specific tissues/cells for the reprogramming process, (ii) the reprogramming efficiencies associated with iPSC generation and (iii) the genomic integrity of the iPSCs generated so that the cells are free from genomic abnormalities such as defective chromosomes so that they are safe to use is cellular therapies/transplantation. Recently we have discovered a new peripheral blood derived reprogramming substrate which is (i) obtainable from almost any patient, without blood mobilisation, (ii) exhibits efficiencies and kinetics of reprogramming suitable for the high-throughput generation of iPSC and (iii) can be used to generate iPSCs relatively free from genomic rearrangements.
Our goals are to progress with the development and application of this new cell type and the iPSCs generated from it to the translational phase of cellular therapies, in drug/toxicology screening and their potential use in the delivery of gene therapies. We are also elucidating the mechanisms behind the striking reprogramming capacity of these cells and using this to understand mammalian pluripotency.