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Dr Sanjay Sinha

Dr Sanjay Sinha

BHF Senior Clinical Research Fellow


Office Phone: 01223 747479/768678

Research themes

Stem Cells:

Research Interests

Vascular smooth muscle cell development and disease

My group studies vascular development and vascular diseases such as aortic aneurysms and atherosclerosis. We have established new methods for generating human vascular smooth muscle cells (SMC) that originate from specific embryonic lineages, using directed differentiation of human embryonic and induced pluripotent stem cells (hESC & hiPSC).

Most recently, we have established an in vitro model for generating ESC-derived epicardium which we then use to generate ‘coronary’-like SMCs. We use these and other systems to study the molecular mechanisms that regulate vascular development. Using patient-derived iPSCs we also model genetic vascular diseases in which smooth muscle cells (SMC) are implicated, e.g. Marfan syndrome (FBN1).

My group is also investigating whether human pluripotent stem cell-derived cells may be used to regenerate the damaged heart, either by direct injection or by generating a vascularised next-generation tissue ‘patch’.  In particular we are interested in the role of the epicardium in regulating this regenerative response.

Keywords

Marfan syndrome ; ES (embryonic stem cells) ; stem cells ; iPS (induced pluripotent stem cells) ; atherosclerosis ; iPSC ; regenerative medicine ; aortic aneurysm

Key Publications

Granata A, Serrano F, Bernard WG, McNamara M, Low L, Sastry P, and Sinha S. An iPSC-derived vascular model of Marfan syndrome identifies key mediators of smooth muscle cell death. Nature Genetics 2017;49:97-109.

Embryological Origin of Human Smooth Muscle Cells Influences Their Ability to Support Endothelial Network Formation. Bargehr J, Low L, Cheung C, Bernard WG, Iyer D, Bennett MR, Gambardella L, Sinha S. Stem Cells Transl Med. 2016 Jul;5(7):946-59.

Robust derivation of epicardium and its differentiated smooth muscle cell progeny from human pluripotent stem cells. Iyer D, Gambardella L, Bernard WG, Serrano F, Mascetti VL, Pedersen RA, Sinha S, Talasila A. Development. 2016 Mar 1;143(5):904.

Vascular Smooth Muscle Cells in Atherosclerosis. Bennett MR, Sinha S, Owens GK. Circ Res. 2016 Feb 19;118(4):692-702.

Robust derivation of epicardium and its differentiated smooth muscle cell progeny from human pluripotent stem cells. Iyer D, Gambardella L, Bernard WG, Serrano F, Mascetti VL, Pedersen RA, Talasila A, Sinha S. Development. 2015 Apr 15;142(8):1528-41.

Temporal and embryonic lineage-dependent regulation of human vascular SMC development by NOTCH3. Granata A, Bernard WG, Zhao N, Mccafferty J, Lilly B, Sinha S. Stem Cells Dev. 2015 Apr 1;24(7):846-56.

Embryonic origins of human vascular smooth muscle cells: implications for in vitro modeling and clinical application. Sinha S, Iyer D, Granata A. Cell Mol Life Sci. 2014 Jun;71(12):2271-88.

Directed differentiation of embryonic origin-specific vascular smooth muscle subtypes from human pluripotent stem cells. Cheung C, Bernardo AS, Pedersen RA, Sinha S. Nat Protoc. 2014 Apr;9(4):929-38.

Myocardin regulates vascular response to injury through miR-24/-29a and platelet-derived growth factor receptor-β. Talasila A, Yu H, Ackers-Johnson M, Bot M, van Berkel T, Bennett MR, Bot I, Sinha S. Arterioscler Thromb Vasc Biol. 2013 Oct;33(10):2355-65.

Embryological-origin-dependent differences in homeobox expression in adult aorta: role in regional phenotypic variability and regulation of NF-κB activity. Trigueros-Motos L, González-Granado JM, Cheung C, Fernández P, Sánchez-Cabo F, Dopazo A, Sinha S, Andrés V. Arterioscler Thromb Vasc Biol. 2013 Jun;33(6):1248-56.

Generation of human vascular smooth muscle subtypes provides insight into embryological origin-dependent disease susceptibility. Cheung C, Bernardo AS, Trotter MW, Pedersen RA, Sinha S. Nat Biotechnol. 2012 Jan 15;30(2):165-73.

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