- Molecular mechanisms of genetic cardiovascular diseases
- iPSC modelling of genetic vascular and neurovascular conditions
- Neurovascular interactions and vascular dementia
- Notch signalling in human cardiovascular system
- Vascular engineering and Nano-medicine
iPSC model of genetic cardiovascular and cerebral vascular conditions
Small vessel diseases are among the key risk factors contributing to cognitive defects of the brain, leading to vascular dementia that has been recognised as the second leading form of dementia after Alzheimer’s disease. However, the underlying molecular mechanisms for such conditions are largely under investigated. The most common type of genetic stroke syndrome CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), caused by NOTCH3 gene mutation, is a typical small vassal disease and provides a valuable model to explore the pathogenesis of vascular dementia. CADASIL is a systemic vascular condition, but has a brain-specific clinical manifestation, suggesting a defect in neurovascular coupling. The communications between vascular cells and neuronal cells happen within the neurovascular unit (NVU) in the brain through either physical contacts or releasing trophic factors. We use the patient-specific iPSC model in conjuction with genome editing (CRISPR/Cas9) to explore functional interactions between neurovascular cells, identify therapeutic targets and conduct drug screen for future treatment of vascular dementia.
Notch signalling in cardiovascular function and diseases
Notch signalling is an evolutionarily conserved pathway that transduces signals between adjacent cells. Notch signalling determines cell fate during embryonic development and are also important in the maintenance of cellular homeostasis in the adult life. Dysregulation of Notch signalling leads to a diverse range of human diseases from cancer to cardiovascular disorders. We are using molecular biology and cell biology tools including high throughput screening to study the role of Notch signalling in cardiovascular and cerebral vascular cells including their differentiation from stem cells, and explore small molecules that could manipulate the signalling in order to achieve targeted treatment for related diseases.
In conjunction with the iPSC research and utilising state-of-art material technologies, we are producing functionalised vascular scaffold that could accommodate patient-specific iPSC-derived vascular cells, in order to create personalised vascular grafts to be used for future regenerative therapy, or as a tissue model for the study of molecular mechanisms of genetic vascular diseases and drug targets.
Nanotechnologies are transforming the capabilities of medical diagnosis and treatments. We are currently producing and functionalising biodegradable nanoparticles to explore their potential for targeted therapy. We also study the molecular mechanisms of the antimicrobial functions of the laser produced novel metal nanoparticles.
Source of funding:
- British Heart Foundation (BHF)
- Medical Research Council (MRC)
- The National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs)
- Manchester Institute for Collaborative Research on Ageing
- Stroke Association
- Alzheimer’s Research UK
- Alzheimer’s Society Manchester and Northwest Network Centre
- The University of Manchester Intellectual Property Limited (UMIP)
- Johnson & Johnson
- Central Manchester and Manchester Children's University Hospitals NHS Trust