Dr Sanjay Sinha
Laboratory: Laboratory for Regenerative Medicine, Cambridge Biomedical Campus. Departmental Affiliation: Medicine
Dr Sanjay Sinha is a British Heart Foundation (BHF) Senior Research Fellow at the University of Cambridge. He completed medical training in Cambridge, followed by cardiology clinical training and a PhD in Manchester. Dr Sinha then carried out post-doctoral studies in the USA with Prof Gary Owens on smooth muscle biology before establishing an independent group at Cambridge. He is also a Consultant in Cardiology and he combines his research work with clinical duties at Addenbrooke’s Hospital, Cambridge, where he treats patients with a wide variety of cardiovascular diseases.
Whole mount confocal image of embryonic chick heart showing epicardium and the localisation of injected hESC-derived epicardial cells (red and green) to their developmental niche (Credit Gambardella and Iyer)
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".
Johannes Bargehr, Will Bernard, Maria Colzani, Laure Gambardella, Madeline McNamara, Sophie McManus, Lay Ping Ong, Felipe Serrano, Priya Sastry, Esther Tan, Loukia Yiangou.
Blood vessel diseases cause heart attacks, strokes and aortic aneurysms (a ballooning then tearing of the main artery in the body). We use human stem cells to generate smooth muscle cells, one of the main cell types that make up the blood vessel wall. If we 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 we are trying to understand how blood vessels become diseased and trying to find new treatments for these diseases. We are also developing ways to transplant our stem cell generated cells to reverse the damage caused by a heart attack.
- 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
- Ackers-Johnson M, Talasila A, Long X, Bot I, Morrell NW, Bennett MR, Miano JM, Sinha S. Myocardin Regulates Vascular Smooth Muscle Cell Inflammatory Activation and Disease. ATVB 2015;35:817-28.4. PMCID:PMC4390125
- 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
- Sinha S, Hoofnagle MH, Kingston PA and Owens GK. TGF-b1 signaling contributes to the development of SMC from embryonic stem cells. AJPhysiol – Cell Physiol 2004;287:C1560-C1568. PMID:15306544