Our Principal Investigators
Professor Chris Denning: In the context of the BHF Centre, Chris Denning (Nottingham PI) and Ralph Hyde (Nottingham researcher) are focussing on establishing GMP-grade conditions for culture and cardiomyocyte differentiation of human embryonic and induced pluripotent stem cell lines. These tasks will be facilitated by our unique robotic platform. In parallel, we will be creating Cas9/CRISPR gene targeted reporter lines to give fluorescent readouts on cardiomyocyte behaviour during challenge, such as apoptosis and necrosis during in vitro culture or transplantation
Professor Thomas Eschenhagen: We are using human cardiomyocytes differentiated from iPSCs to generate human engineered heart tissue (EHT). EHTs are three-dimensional human cardiac constructs that resemble native myocardium. These constructs have been y used successful to remuscularize injured hearts in a small animal model. We are currently working on the optimization of EHT geometry, culture conditions and the plant to start a large animal study to bring this approach closer to a clinical application.
Richard Jabbour from Sian Harding´s group has visited us in Hamburg to learn how to generate mesh-structured human EHTs. He has successfully set up this model in London and by now has transplanted the first mesh structured EHTs in a rabbit model.
Professor Julia Gorelik: Julia Gorelik’s laboratory is studying maturation of functional nanodomains in hiPS-CMs.
Professor Ipsita Roy: Ipsita Roy is an expert in natural biomaterials and their biomedical applications. She was awarded the prestigious Inlaks Scholarship to study for her Ph.D. at the University of Cambridge, UK. Her postdoctoral work was at the University of Minnesota, USA, at the Bioprocess Technology Institute. She has been at the University of Westminster since 2000 and leads the Applied Biotechnology Research Group in the Faculty of Science and Technology. Her group is currently focussed on the production of novel polyhydroxyalkanoates (PHAs), a group of FDA-approved natural polymers and their characterisation. She has pioneered the production of PHAs from Gram positive bacteria which lack immunogenic properties and hence are excellent materials for medical applications. Her group is involved in the application of PHAs in the area of hard tissue engineering, soft tissue engineering, medical device development, wound healing and drug delivery.
Prof Michael Schneider: We previously found that intramyocardial injection of cardiac progenitor cells (CPCs) at time of ischemia improves cardiac function 12 weeks later. Given poor long-term engraftment in our studies and many others’, the consensus is that early paracrine effects are the probable cause of the benefits observed,
including direct effects on cardiomyocytes but also macrophages as key players in the response to injury.
The major advancements of our team working on paracrine circuits for heart repair by cardiac stem cells focus on the protective effects on cardiomyocytes and macrophages. Using human iPS-derived cardiomyocytes as a platform, we found that conditioned-media from cardiac progenitors determines protection from cell death and apoptosis triggered by different stresses. Our complementary studies demonstrate that progenitors’ paracrine effects include disruption of the pro-inflammatory (“M1”) programme induced by GM-CSF/LPS/IFN, and promoting instead the formation of anti-inflammatory (“M2”) macrophages. We are using single cell technologies as well as high-throughput approaches to define and validate candidate factors mediating the specify effects described above.
From a quantitative and qualitative point of view, the magnitude of protection and the anti-inflammatory effects do not just merely ovide a mechanistic implication for the improvement in cardiac function determined by intra-myocardial injection of progenitors at time of myocardial infarction. These findings allow us to envision cell-free therapies based on delivery of the factors mediating cardiomyocytes cell death prevention and immunomodulation as well as adjuvants to other therapies including as a pro-survival treatment of iPS-derived cardiomycoytes to be used as a cell therapy.
Professor Molly Stevens: Molly Stevens designs and develops materials-based and new imaging approaches towards cardiac repair and regeneration. Exemplars of her research include conductive materials, scaffolds, patches and extracellular vesicle-based therapeutic strategies. More information can be found at www.stevensgroup.org.
Dr Daniel Stuckey: Dr Stuckey's research focuses on developing and applying novel multi-modality imaging approached for the investigation of cardiomyopathy and therapy. Using serial in vivo cardiac MRI, ultrasound and PET/SPECT/CT, he investigates the mechanisms that underlie cardiac disease and result in heart failure.
Daniel is recognised as an international leader in preclinical cardiovascular imaging and through collaboration with the Imperial Centre for Regenerative Medicine. His work can provide a translational insight into the mechanisms through which cell and tissue engineered therapies can benefit the heart. Specifically, Daniel is coordinating the in vivo measurements of cardiac structure, function and viability after therapy using MRI, ultrasound and nuclear imaging. He also applies techniques for in vivo tracking of stem cell and biomaterial location as well as ultrasound guided cell delivery methods. Through collaboration with the world leading teams within the BHF’s Regenerative Medicine Centres, Daniel aims to use imaging to guide the next generation of regenerative therapies.
- The effects of conductive polymers on myocardial tissue
- Cardiac fibroblasts proliferation and activation when cultured in vitro on myocardial slices
- New tissue clearing imaging methodologies for three-dimensional visualization of cardiac tissue
- Myocardial slice as a platform to study the mechanisms of functional integration and electrical coupling of transplanted cells with the recipient myocardium
- Structural and functional response of myocardial slices to prolonged changes in mechanical load in vitro
- Metabolic response of myocardial slice to mechanical load and prolonged in vitro culture.
Professor Godfrey Smith: Godfrey Smith’s interests include examination of the subcellular processes involved in excitation-contraction coupling of cardiac muscle using biophysical and biochemical techniques. Methodologies include fluorescence microscopy, electrophysiology and confocal imaging.