Professor Adrian Isaacs' Group

Professor Adrian Isaacs did his undergraduate studies in molecular biology and genetics at the University of Manchester. As part of those studies, he spent one year working at the Mayo Clinic in Florida with Professor John Hardy and Mike Hutton, where he was part of the team that discovered that mutations in MAPT cause frontotemporal dementia. This set him on the path to research into neurodegenerative diseases. Professor Isaacs then did his PhD at Oxford University and post-doctoral studies at Harvard Medical School before coming to UCL to start their own research group.

• ORCID: 0000-0002-6820-5534

Our research

We investigate the molecular mechanisms that cause frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) also known as motor neuron disease. We are particularly interested in the C9orf72 gene, which is a common cause of both FTD and ALS and the CHMP2B gene, which is a rare cause of FTD. We use a multidisciplinary approach including disease modelling in mice, Drosophila and induced pluripotent stem cell (iPSC)-derived neurons, which we combine with analysis of biosamples from people with FTD and ALS. We are working to translate our basic research into potential therapies and are currently developing small molecule and gene therapy approaches for FTD and ALS. In addition, we develop biomarkers to enable clinical trials of new treatments. For more information see https://adrianisaacslab.com/research/

Selected publications

• Mizielinska S, Grönke S, Niccoli T, Ridler CE, Clayton EL, Devoy A, Moens T, Norona FE, Woollacott IO, Pietrzyk J, Cleverley K, Nicoll AJ, Pickering-Brown S, Dols J, Cabecinha M, Hendrich O, Fratta P, Fisher EM, Partridge L, Isaacs AM. C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins. Science. 2014; 345:1192-1194.
• Wilson KM, Katona E, Glaria I, Swift IJ, Sogorb-Esteve A, Heller C, Bouzigues A, Heslegrave AJ, Patil S, Mohapatra S, Liu Y, Goyal J, Sanchez-Valle R, Laforce R, Synofzik M, Rowe JB, Finger E, Vandenberghe R, Butler CR, Gerhard A, van Swieten J, Seelaar H, Borroni B, Galimberti D, de Mendonça A, Masellis M, Tartaglia C, Otto M, Graff C, Ducharme S, Malaspina A, Zetterberg H, Boyanapalli R, Rohrer JD, Isaacs AM. Development of a sensitive trial-ready poly(GP) CSF biomarker assay for C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2022 Jul;93(7):761-771.
• Milioto C, Carcolé M, Giblin A, Coneys R, Attrebi O, Ahmed M, Harris SS, Lee BI, Yang M, Ellingford RA, Nirujogi RS, Biggs D, Salomonsson S, Zanovello M, De Oliveira P, Katona E, Glaria I, Mikheenko A, Geary B, Udine E, Vaizoglu D, Anoar S, Jotangiya K, Crowley G, Smeeth DM, Adams ML, Niccoli T, Rademakers R, van Blitterswijk M, Devoy A, Hong S, Partridge L, Coyne AN, Fratta P, Alessi DR, Davies B, Busche MA, Greensmith L, Fisher EMC, Isaacs AM. PolyGR and polyPR knock-in mice reveal a conserved neuroprotective extracellular matrix signature in C9orf72 ALS/FTD neurons. Nat Neurosci. 2024 Apr;27(4):643-655.
• Kempthorne L, Vaizoglu D, Cammack AJ, Carcolé M, Suklai P, Muralidharan B, Kroll F, Moens TG, Yshii L, Verschoren S, Hölbling BV, Katona E, Mikheenko A, Coneys R, de Oliveira P, Zhang Y, Jansen K, Daughrity LM, McGown A, Ramesh TM, Van Den Bosch L, Rahim AA, Petrucelli L, Rihel J, Isaacs AM. Dual-targeting CRISPR-CasRx reduces C9orf72 ALS/FTD sense and antisense repeat RNAs in vitro and in vivo. Nat Commun. 2025 Jan 8;16(1):459. doi: 10.1038/s41467-024-55550-x.
• Giblin A, Cammack AJ, Blomberg N, Anoar S, Mikheenko A, Carcolé M, Atilano ML, Hull A, Shen D, Wei X, Coneys R, Zhou L, Mohammed Y, Olivier-Jimenez D, Wang LY, Kinghorn KJ, Niccoli T, Coyne AN, van der Kant R, Lashley T, Giera M, Partridge L, Isaacs AM. Neuronal polyunsaturated fatty acids are protective in ALS/FTD. Nat Neurosci. 2025 Apr;28(4):737-747.

Members of the lab

• Dr Alexander Cammack
• Miss Cristina Marisol Castillo Bautista
• Ms Ava Devaney
• Ms Alessia Fisher
• Dr Bailey Hewlett
• Dr Paolo Marchi
• Mr Ekhlasur Rahman
• Dr Martha Roberts
• Dr Stephanie Anne Taylor