Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Blood-brain barrier (dys)function and regulation of brain water homeostasis in CNS pathologies

 

We investigate mechanisms of blood-brain barrier (dys)function in neurodegenerative diseases and brain injuries using patient-derived stem cells, gene editing (CRISPR-Cas 9) and organ-on-a-chip technologies.

Dementia is a multifactorial and heterogeneous condition and leading cause of morbidity and mortality. Our work aims to answer the question: how does inflammation-mediated blood-brain barrier (BBB) dysfunction lead to the development of neurodegeneration and dementia? We design and build innovative dynamic 3D multicellular in vitro model to accurately recapitulate the brain and BBB function under neurodegenerative-relevant conditions using human-derived iPSCs.

Increasing evidence supports the involvement of BBB dysfunction in neurodegenerative disorders including Parkinson’s and Alzheimer's; it is evident that this dysfunction happens even before the onset of dementia. In-depth understanding of the cell-cell interactions and signalling pathways between the core elements of the BBB will help in defining therapeutic targets for the prevention of dementia.

In previous work, we identified several molecular targets that contribute to barrier integrity function in astrocytes and pericytes and developed 3D microfluidic BBB-on-a-chip models. We will build on this expertise and establish advanced models using patient-derived iPSC lines in order to investigate the role of neuroinflammation and the glymphatic system under mechanobiological stimuli and determine how biophysical factors such as blood pressure, flow rate and heartbeat control brain waste clearance. 

Our work will provide new tools to understand lifelong brain health, describe the basis of BBB dysfunction in the occurrence and development of dementia, and provide a platform to develop new treatments for neurodegeneration. 

 

Our team

Key Publications

What's new

Related research themes

We host a number of internationally recognised neuroscience groups, with expertise in a wide range of experimental and computational methods.
Neuroscience

We host a number of internationally recognised ...