Professor Sanjay Sinha
Cardiovascular diseases
Email: sinha@stemcells.cam.ac.uk | Departmental Affiliation: Medicine
Research
Plain English: Blood vessel diseases cause heart attacks, strokes and aortic aneurysms (a ballooning then tearing of the main artery in the body). The Sinha Group uses human stem cells to generate smooth muscle cells, one of the main cell types that make up the blood vessel wall. If they use skin cells from patients with vascular diseases to make stem cells then the smooth muscle cells from those (induced) stem cells will have the same abnormalities as in the patient, thus providing a way to generate a "disease-in-a-dish". With these and other approaches they are trying to understand how blood vessels become diseased and trying to find new treatments for these diseases. They are also developing ways to transplant our stem cell generated cells to reverse the damage caused by a heart attack.
Research Focus: The Sinha lab’s overall aim is to develop new treatments for cardiovascular diseases, using their expertise in cardiovascular development, regeneration and disease modelling. They have pioneered the generation of embryonic lineage-specific vascular smooth muscle cells from human embryonic stem cells (hESC) and induced pluripotent stem cells, using chemically defined conditions. They 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, they are they are generating a detailed multiomic and spatial atlas of human heart development and modelling key developmental niches and events in vitro using hESC-based 3D system to define key regulatory mechanisms in humans.
Finally, they 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”.
Sinha Group photo
Key Publications
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Knight-Schrijver VR, Davaapil H, ... Sinha S. A single-cell comparison of adult and embryonic human epicardium defines the age-associated changes in epicardial activity. Nature Cardiovasc Res 2022;1:1215-1229.
- Colzani M, Malcor JD, Hunter EJ, Bayraktar S, Polkinghorne M, Krieg T, Cameron R, Best S, Farndale RW, Sinha S. Modulating hESC-derived cardiomyocyte and endothelial cell function with triple-helical peptides for heart tissue engineering. Biomaterials. 2020 Dec 16;269:120612. Epub ahead of print. PMID: 33385684. PMCID: PMC7884910
- Gambardella L, McManus S, Moignard V, Sebukhan D, Delaune A, Andrews S, Bernard WG, Morrison M, Riley PR, Göttgens B, Le Novère N and Sinha S. BNC1 regulates epicardial heterogeneity and function. Development 2019;146: dev174441 (Epub) doi: 10.1242/dev.174441: PMID: 31767620
- Bargehr J, Ong LP, Colzani M, Davaapil H, Hofsteen P, Bhandari S, Gambardella L, Le Novère N, Iyer D, Sampaziotis F, Weinberger F, Bertero A, Leonard A, Bernard WG, Martinson A, Figg N, Regnier M, Bennett M, Murry CE, and Sinha S. Human Embryonic Stem Cell-Derived Epicardial Cells Augment Cardiomyocyte-Driven Heart Regeneration. Nature Biotech 2019;37:895-906. PMID: 31375810
- 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
- Iyer D, Gambardella L, Bernard W, Serrano F, Mascetti VL, Pedersen RA, Talasila A, Sinha S. Robust Derivation of Epicardium and Its Differentiated SMC progeny from Human PSCs. Development 2015;142:1528-41. PMCID:PMC4392600
- Cheung C, Bernardo AS, Trotter MW, Pedersen RA, Sinha S. Generation of human vascular SMC subtypes provides insights into embryological origin-dependent disease susceptibility. Nature Biotech 2012;30:165-73. PMCID:PMC3272383