Dr Sanjay Sinha
Laboratory for Regenerative Medicine, Cambridge Biomedical Campus
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".
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.
- 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
- Yoshida T, Sinha S, Dandre F, Wamhoff BR, Hoofnagle MH, Olson EN and Owens GK. Myocardin is a key regulator of CArG-dependent transcription of multiple smooth muscle marker genes. Circ Res 2003;92:856-64. PMID:12663482