Prof Adrian Isaacs
Professor of Neurodegenerative Disease
Neurodegenerative Diseases
UCL Queen Square Institute of Neurology
- Joined UCL
- 17th Jul 2008
Research summary
My group studies the molecular basis of two related neurodegenerative diseases: frontotemporal dementia (FTD) and motor neuron disease (MND). FTD is a common form of young-onset dementia and is characterised by changes in personality and language. MND is characterised by progressive weakness and paralysis. FTD and MND can be caused by mutations in the same gene, and can co-occur in the same individual. Therefore, FTD and MND are now considered overlapping clinical syndromes with common causes. Our approach is to generate cellular and animal models of genetically inherited forms of FTD and MND, in parallel with analysis of patient iPSC-neurons and brain tissue, in order to elucidate the mechanisms that lead to neuronal dysfunction and death. We are also developing drug screens based on this knowledge to identify potential therapeutics. Our main focus is on two disease genes, CHMP2B and C9orf72. CHMP2B causes frontotemporal dementia linked to chromosome 3, a rare form of FTD that occurs in a large Danish family. CHMP2B is part of ESCRT-III (endosomal sorting complex required for transport-III), a multi-protein complex required for degradation events in the autophagy and endosome-lysosome pathways. We have shown that mutant CHMP2B affects degradation in both of these pathways and are interested in how defects in these essential lysosomal degradation pathways specifically lead to impaired neuronal function. To address this question we are using a range of imaging and proteomic approaches in our collection of models and patient tissue. We are also testing therapeutic approaches that can alleviate endo-lysosome dysfunction in these models.
Teaching summary
I am a tutor and lecturer for the MSc in Clinical Neuroscience based at the UCL Institute of Neurology and also a co-convenor for the Cellular and Molecular Mechanisms of Disease module.
Education
- Institute of Education
- Other Postgraduate qualification (including professional), ATQ01 - Successfully completed an institutional provision in teaching in the HE sector | 2012