Our team uses a combination of genomic approaches in mouse models, patient neurons and tissues to define the roles of RNA-binding proteins related to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD), with the goal of comparing regulatory networks to identify mechanisms by which aggregation-prone RNA-binding proteins, including TDP-43 and FUS/TLS, contribute to neuronal function.
We recently identified STMN2 as the most altered transcript in TDP-43 deficient cells and ALS patients motor neurons. We are now investigating the impact of STMN2 loss in neurodegeneration and its potential therapeutic target in TDP-43 proteinopathies. We also explore disease mechanisms and develop therapeutic strategies for neurological diseases linked to microsatellite expansions including ALS/FTD associated with C9ORF72 expansions, and Huntington’s disease.
We now explore the convergence of disease- and aging-related mechanisms in mediating nuclear dysfunction in the nervous system. We investigate mechanisms influencing aberrant translation of expanded C9ORF72 transcripts, and closely collaborate with industrial partners to develop new therapeutic strategies including antisense oligonucleotides (ASO) and immunotherapy approaches for ALS/FTD. Finally, we use small-molecule and genetic screens - including high-content optical screens - to identify modifiers of disease-associated phenotypes and new therapeutic targets for neurodegenerative disease.