Our research is focused on gaining fundamental understanding of stem cells and regeneration and to use this knowledge to develop new models, diagnostics and therapies to improve human health.
The interests of the centre focus on four main research themes:
Stem cell biology
This research theme is focused on the mechanisms underpinning the emergence of tissue stem cells from embryonic progenitors in a variety of systems. This includes the endothelial and haematopoietic systems, thymic epithelium, nervous system, liver, pancreas, testis, and musculoskeletal tissue. Several groups are also investigating the early lineage decisions of embryonic stem (ES) cells, specifically the key regulatory molecules that direct ES cell self-renewal and differentiation.
Developing key research tools
Large-scale analyses using functional genomic techniques enable us to map out key molecular mechanisms underpinning stem cells (Simon Tomlinson). We have established innovative genetic engineering technologies to generate genetically manipulated stem cells for use in a wide range of projects at CRM (Andrew Smith).
Alexander Medvinsky, Andrew Smith, Bruno Péault, Charles ffrench-Constant, Clare Blackburn, Dónal O’Carroll, Ian Chambers, Kamil R Kranc, Katrin Ottersbach, Sally Lowell, Simon Tomlinson, Steve Pollard, Stuart Forbes, Val Wilson.
Tissue homeostasis and repair
Self-renewal and differentiation of stem cells is modulated in an area of tissue known as a stem cell ‘niche’. The ability of specific niche cell types and intrinsic factors in this microenvironment to maintain tissue homeostasis and initiate repair is being addressed in this theme.
We use a range of experimental systems to study the cellular and molecular mechanisms of stem cell activation during repair and regeneration in the brain, liver, thymus and haematopoietic system.
Bruno Péault, Charles ffrench-Constant, Clare Blackburn, Stuart Forbes, Anna Williams.
Research in this theme examines the factors, mechanisms and technologies that enable us to generate pluripotent stem cells directly from adult cells (reprogramming). Reprogramming holds great potential for new medical applications such as cell replacement therapies, however the process remains inefficient.
The goal of this research is to improve the efficiency of the reprogramming technology and develop safer strategies for cell fate change.
In an alternative approach, the natural reprogramming that occurs in Schwann cells following mycobacterium leprae infection is used to identify potential therapeutic strategies for direct conversion in vivo.
Abdenour Soufi, Anura Rambukkana, Keisuke Kaji.
Translational and clinical programmes
The translational aspect of this theme focuses on developing cell-based therapies, drug-based regenerative medicines and disease models using cell types derived from human embryonic stem cells or induced pluripotent stem cells.
The essential knowledge obtained from the basic biology research themes will inform and enable the translational and clinical programmes to deliver novel treatments and technologies.
- We aim to develop drug-based regenerative medicines for multiple sclerosis (Anna Williams, Charles ffrench-Constant), and cell-based therapies and screening platforms for the liver (David Hay, Lesley Forrester, Stuart Forbes). This will involve toxicity screening of candidate drugs and developing autologous monocyte/macrophages for therapeutic use in hepatic cirrhosis.
- A collaborative project, NOVOSANG, to generate red blood cells for transfusion from adult haematopoietic stem cells and human embryonic stem cells is currently underway (Lesley Forrester).
- The BHF Centre for Vascular Regeneration is aimed at delivering vascular repair and regeneration, combining high impact basic science with translation into the clinic. The Centre has been set up in close collaboration with the University/BHF Centre for Cardiovascular Science.
- The STEMBANCC Innovative Medicines Consortium is a joint industry/academia project is designed to generate and characterise high quality human induced pluripotent stem (iPS) cell lines to study a range of chronic diseases (e.g. diabetes and dementia) and test for drug efficacy and safety (Simon Tomlinson).
- Several CRM research groups have human disease modelling programmes in partnership with local, UK and international collaborators (Dave Hay, Ian Wilmut, Tilo Kunath, Siddharthan Chandran).
Clinical trial activities
- The Forbes group has commenced the world’s first randomised controlled trial of stem cell therapy for liver cirrhosis - the REALISTIC study (Repeated Autologous Infusions of Stem Cells in Cirrhosis).
- The Chandran group is a collaborator on the MS-SMART (Multiple Sclerosis - Secondary Progressive Multi-Arm Randomisation Trial).