BMI Seminar // Mootaz Salman "Defining mechanisms of blood-brain barrier dysfunction in neurodegenerative diseases using advanced organ-on-a-chip models"

Neurodegenerative diseases are multifactorial and heterogeneous conditions 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 whether we can stop it?  Increasing evidence supports the involvement of BBB dysfunction in neurodegenerative disorders including Parkinson’s, Alzheimer's and small vessel dementia; 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 and validating new therapeutic targets for the prevention of dementia.
In our work, we developed advanced microfluidic 3D BBB-on-a-chip models using patient-derived iPSCs and human primary cells and identified a number of molecular targets that contribute to barrier integrity and function in astrocytes and pericytes. Our work provides new tools to understand lifelong brain health, describe the basis of BBB dysfunction in the occurrence and development of neurodegeneration, and provides a platform to develop new treatments for dementia and related CNS pathologies.