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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

Mootaz Salman wins SEB 2024 President’s Medal

Dr Mootaz Salman has been awarded the Society for Experimental Biology (SEB) 2024 President’s Medal for the Cell Biology Section

Mootaz Salman wins a BBSRC Pioneer Award

Mootaz Salman has won, (together with Professor Roslyn Bill of Aston University) a grant from the BBSRC to study mechanisms involved in brain waste clearance using organ-on-chip technology.

Career Development Fellowship awarded to Mootaz Salman could pave the way for early intervention in neurodegenerative diseases

Dr Mootaz Salman has been awarded the MRC Career Development Fellowship.

Can 3D models of brain-on-chip help in developing new treatments?

Fascinating new TEDx Talk from Departmental Research Lecturer and Leverhulme Fellow Dr Mootaz Salman.

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 ...