SMC development, lineage and disease
Our work combines the fields of stem cell biology and vascular biology to provide new insights into vascular smooth muscle cell development and novel treatments for vascular diseases. We have developed in vitro systems using murine and human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells in which pure populations of mature contractile vascular SMCs may be generated.
Modelling genetic diseases using patient-derived iPSCs
A major focus of the group is to use our established in vitro system and patient-derived iPS cells to model genetic disorders in which there is a key SMC phenotype. Marfan syndrome, in which aortic SMC loss and matrix breakdown lead to aortic dissection, is the exemplar for this approach.
Myocardin as a key regulator of vascular disease
We have carried out the first gain- and loss-of function studies in vivo to identify a new role for Myocardin in regulating the vascular injury response and atherosclerosis.
Granata A, Bernard WG, Zhao N, McCafferty J, Lilly B and Sinha S. Temporal- and embryonic lineage-dependent regulation of human vascular SMC development by Notch3. Stem Cells & Dev 2015 (in press).
Cheung C, Bernardo AS, Pedersen RA and Sinha S. Directed differentiation of embryonic origin-specific vascular smooth muscle subtypes from human pluripotent stem cells. Nature Protocols 2014;9:929-38.
Talasila A, Yu H, Ackers-Johnson M, Bot M, van Berkel T, Bennett MR, Bot I and Sinha S. Myocardin regulates neointima formation after vascular injury through miR-24 and -29a mediated inhibition of PDGF-Rb and cell migration. ATVB 2013;33:2355-65.