Molecular and Cellular Medicine (MCM) has research interests and strength in healthy ageing and chronic diseases, bridging the other research themes of YBRI. It has particular focus on epithelial cancers, urothelium, skin, diabetes, osteoarthritis and neurodegenerative disorders.
MCM includes a diverse range of state-of-the-art research expertise covering everything from experimental platforms to therapeutic interventions. Examples include stem and cell-type systems as platforms for studying mechanisms of disease, to the pioneering of novel therapeutics and interventions, including novel technologies for diagnostics and point-of-care devices.
MCM provides a clear pathway for researchers to collaborate on multidisciplinary projects, enabling basic through to translational studies. We also host the unique Jack Birch Unit for Molecular Carcinogenesis and its related NHS-approved urothelial tissue bank, URoBank.
Healthy Ageing and Chronic Disease
Failure of normal tissue regulatory mechanisms occurs with age, culminating in chronic and degenerative diseases of ageing. York has major research strengths in the underpinning cellular mechanisms involving stem cells, commitment and differentiation - the processes by which cells specialise to form and maintain functional, healthy tissues.
Fundamental mechanisms of healthy ageing and chronic diseases are supported using experimental stem and cell type-specific systems. With strength from different model organisms (yeast, xenopus, drosophila, zebra fish, mice) combined with human cell/tissue systems.
These experimental systems provide a basis for studying development (Pownall), nuclear organisation (Coverley), genomes (Mason, Noy), chromatin regulation (Holding), ion channels (Brackenbury), subcellular compartmentalisation and trafficking (Bryant, MacDonald) and cell signalling (Evans) in health and disease.
Cancer: from carcinogenesis to malignancy
Bridging the two YBRI themes of MCM and Immunology, Haematology and Infection (IHI) is cancer. With IHI focusing on haematological malignancies; MCM has a major focus on adult epithelial cancers, known as carcinomas.
Research into adult epithelial cancers is built on the strong 30 year foundation of the Jack Birch Unit for Molecular Carcinogenesis (JBU), which is supported by local charity, York Against Cancer. The JBU focuses on urothelial (bladder and urinary tract) cancers. In vitro approaches are used to study normal human urothelial cells and tissue regulatory controls and how these processes are dysregulated during carcinogenesis and malignant progression (Southgate, Baker). Cell and molecular biology approaches are combined with data-rich transcriptomic analyses of in house and public datasets to identify tissue-specific and common cancer pathways using informatics (Mason) and machine learning approaches (Smith). By stratifying cancer into subgroups the aim is to target effective therapies.
Breast cancer is an area which is developing at York. Areas of particular interest are to understand the migration and invasion of metastatic breast cancer cells (Brackenbury); and the role of hormones in driving breast cancer and why people respond differently to the same treatment (Holding).
Understanding the underlying mechanisms of cell commitment and its dysregulation in disease is CIZ1 (Coverley). Study of the specific CIZ1B variant of the CIZ1 protein has led to a blood test for the early detection of lung cancer by University of York spin-out CizzleBiotech.
Degenerative diseases of ageing
Many disease conditions are associated with the ageing process. Molecular mechanisms of neurodegenerative diseases such as Alzheimer’s Disease (Quinn), Amyotrophic lateral sclerosis (ALS), Frontotemporal Dementia (Sweeney, Chen) and Parkinson’s Disease are particular areas of focus which bridge MCM and the Neuroscience themes.
Osteoarthritis is being tackled using tissue engineering and regenerative medicine approaches to study how functional mesenchymal tissues (bone and cartilage) are formed and can be targeted (Genever). This is complemented by research into mechanisms underpinning muscular plasticity and diseases such as muscular dystrophy (Blanco, Willems).
How the hormone insulin regulates membrane traffic in fat and muscle cells is an important line of basic and applied research. Defects in this transport system underlie Type-II Diabetes, a debilitating disease whose incidence is increasing worldwide at an exponential rate (Bryant, Brzozwski).
Novel therapeutics and interventions
The development of novel therapeutics and interventions is multifaceted and uses a variety of approaches, such as tissue engineering and regenerative medicine, chemical glycomedicine (Fascione, Willems), development of novel insulin analogues for oral delivery (Brzozowski), drug discovery (Clark), design and synthesis (O’Brien).
There is also research combining artificial intelligence (AI) and molecular diagnostics for molecular diagnostic informed disease, early melanoma diagnostic technologies and skin cancer treatment (Prow). Read more about our diagnostic technologies and point-of-care devices on the Biomedical Technologies page.
Carbohydrates play key roles in a wide variety of cellular processes. When attached to proteins, they can, for example, regulate protein stability and mediate cell-cell and cell-pathogen interactions. These glycoconjugates are often extended into complex, branched carbohydrate structures. The exact structures of the various glycoconjugates are determined by the enzymes that are responsible for building up, remodelling and breaking down carbohydrate chains. Defects in several of these enzymes, as well as in the glycoconjugates themselves, have been found to be at the basis of various human diseases.
Research at York looks at glycan biosynthesis and degradation in health and disease. Specifically viral invasion, cancer and imaging/treatment of lysosomal storage diseases (Davies), tumour metastasis, bacterial recognition and the immunological response (Fascione) and muscular dystrophies (Willems).
There is focus on deciphering and in vivo perturbation of the roles that carbohydrates play in the aetiology of disease. To develop chemical biology tools, which can be applied in innovative new 'chemical glycomedicine' approaches for the prevention and treatment of disease. To translate novel chemistry into living systems, from where the complex roles of carbohydrates can be probed further at a dynamic cellular level (Fascione, Willems).