The team investigates the molecular mechanisms driving neurodegeneration in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer’s disease and in repeat expansion diseases including Huntington’s disease and X-linked Dystonia Parkinsonism (XDP). We use innovative preclinical models and functional genomics approaches to identify new therapeutic targets for neurodegenerative diseases. We have established collaborations with academic and pharmaceutical partners to develop novel approaches to therapy, including RNA-targeting antisense oligonucleotides and immunotherapies for ALS and FTD.
What’s happening?
Publications
Impaired nucleocytoplasmic transport in SOD1-mediated ALS
Molecular Neurodegeneration (2026) DOI: https://doi.org/10.1186/s13024-026-00930-8
Impaired nucleocytoplasmic transport (NCT) has emerged as a shared pathogenic mechanism in various neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). Although mutations in the gene encoding superoxide dismutase 1 (SOD1) account for approximately 20% of familial ALS cases, the impact of mutant SOD1 accumulation on the NCT remains unclear.
Blocking RAN translation without altering repeat RNAs rescues C9ORF72-related ALS and FTD phenotypes
Science (2026) DOI: https://doi.org/10.1126/science.adv2600
The expansion of the hexanucleotide repeat GGGGCC in the noncoding region of the C9ORF72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Jiang et al. investigated whether the pathological effects were driven by aggregated RNA foci or by the dipeptide repeat proteins (DPRs) translated from the sense– and antisense repeat–containing transcripts (see the Perspective by Arnold and La Spada).
Lysosomal escape and TMEM106B fibrillar core determine TDP-43 seeding
BioRxiv (2025) DOI: https://doi.org/10.64898/2025.12.19.695531.
Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) shows striking clinical and neuropathological heterogeneity, yet a systematic analysis of subtype-specific features and inter-patient variability was missing. We treated human neurons and neuron-like cells with 30 postmortem brain samples and quantified neoaggregate formation, loss of function and changes in the TDP-43 interactome to define determinants of seeding outcomes.
Thai B. Nguyen, Ricardo Miramontes, Carlos Chillon-Marinas, Roy Maimon, Sonia Vazquez-Sanchez, Alice L. Lau, Nicolette R. McClure, Zhuoxing Wu, Keona Q. Wang, Whitney E. England, Monika Singha, Jennifer T. Stocksdale, Marie Heath, Ki-Hong Jang, Sunhee Jung,Karen Ling, Paymann Jafar-nejad, Jharrayne I. McKnight, Leanne N. Ho, Osama Al Dalahmah, Richard L. M. Faull, Joan S. Steffan, Jack C. Reidling, Cholsoon Jang, Gina Lee, Don W. Cleveland, Clotilde Lagier-Tourenne, Robert C. Spitale & Leslie M. Thompson
Nature Neuroscience (2025) DOI:https://doi.org/10.1038/s41593-024-01850-w
