My lab's overall aim is to develop new treatments for vascular diseases, in particular those involving vascular smooth muscle cells (SMC), using a stem cell based approach. We have pioneered the generation of embryonic lineage-specific vascular SMC, through the lateral mesoderm, paraxial mesoderm, neural crest and epicardium, from human embryonic stem cells (hESC) and induced pluripotent stem cells, using chemically defined conditions. We have utilised this system to model genetically triggered aortopathies, such as Marfan and Loeys-Dietz syndromes. These "disease-in-a-dish" models are being used to understand the pathobiology of these conditions and to screen for new treatments. Additionally we are testing the regenerative potential of hESC-derived epicardium and other cardiovascular cell types for heart repair after myocardial infarction, either through direct injection or in the form of an in vitro generated myocardial "patch".
Modulating hESC-derived cardiomyocyte and endothelial cell function with triple-helical peptides for heart tissue engineering.
Colzani M, Malcor JD, Hunter EJ, Bayraktar S, Polkinghorne M, Krieg T, Cameron R, Best S, Farndale RW, Sinha S.
Biomaterials. 2020 Dec 16;269:120612. doi: 10.1016/j.biomaterials.2020.120612. Online ahead of print.PMID: 33385684
Aortic “Disease-in-a-Dish”: Mechanistic Insights and Drug Development Using iPSC-Based Disease Modeling
Hongorzul Davaapil, Deeti K. Shetty and Sanjay Sinha
Front. Cell Dev. Biol., 28 October 2020 | https://doi.org/10.3389/fcell.2020.550504
Laure Gambardella, Sophie A. McManus, Victoria Moignard, Derya Sebukhan, Agathe Delaune, Simon Andrews, William G. Bernard, Maura A. Morrison, Paul R. Riley, Berthold Göttgens, Nicolas Gambardella Le Novère, Sanjay Sinha. Development. 2019 Dec 13;146(24):dev174441. doi: 10.1242/dev.174441. PMID: 31767620
Epicardial cells derived from human embryonic stem cells augment cardiomyocyte-driven heart regeneration
Johannes Bargehr, Lay Ping Ong, Maria Colzani, Hongorzul Davaapil, Peter Hofsteen, Shiv Bhandari, Laure Gambardella, Nicolas Le Novère, Dharini Iyer, Fotios Sampaziotis, Florian Weinberger, Alessandro Bertero, Andrea Leonard, William G Bernard, Amy Martinson, Nichola Figg, Michael Regnier, Martin R Bennett, Charles E Murry, Sanjay Sinha. Nat Biotechnol. 2019 Aug;37(8):895-906. doi: 10.1038/s41587-019-0197-9. Epub 2019 Aug 2.
An iPSC-derived vascular model of Marfan syndrome identifies key mediators of smooth muscle cell death.
Granata A, Serrano F, Bernard WG, McNamara M, Low L, Sastry P, Sinha S.
Nat Genet. 2017 Jan;49(1):97-109. doi: 10.1038/ng.3723. Epub 2016 Nov 28.
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. doi: 10.1242/dev.136143.
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. doi: 10.1038/nbt.2107.