Research
Publications
Our research is dedicated to understanding disease mechanisms and provide this information through rigorous, multidisciplinary peer reviewed publications. Follow our journey as we explore new projects and breakthroughs in neurodegenerative disease research. Read more to learn about our new innovative and exciting research.
Featured Publications
Ghaffari, L. T. et al. 2025. Am. J. Physiol.-Cell Physiol
Neuronal activity-dependent gene dysregulation in C9orf72 i3Neuronal models of ALS/FTD pathogenesis
Our recent study using iPSC-derived cortical neurons reveals how neuronal activity drives gene dysregulation in C9ORF72-linked ALS/FTD. We uncover synaptic dysfunction, peroxisomal dysregulation, and NPAS4-linked transcriptional shifts, highlighting key disease-modifying pathways. Explore our research and generate your own discoveries using our interactive dataset included in the link in the article.
All Publications
Ghaffari, L et al. 2023. iScience
Differential response of C9orf72 transcripts following neuronal depolarization
Neuronal activity is a crucial modifier of biological processes in health and neurodegenerative disease contexts. Here, we show that prolonged membrane depolarization in healthy human iPSC-cortical neurons leads to a significant alternative regulation of specific C9orf72 transcript variants. However, the same response is not observed in cortical neurons derived from patients with the C9-NRE mutation. These findings reveal the impact of depolarization on C9orf72 transcripts, and how this response diverges in C9-NRE-carriers, which may have important implications in the underlying unique clinical associations of C9-NRE transcripts and disease pathogenesis.
Ghaffari, L. et al. 2022. Front. Mol. Neurosci.
Breakdown of the central synapses in C9orf72-linked ALS/FTD
Cortical hyper-excitability is observed pre-symptomatically across disease-causative genetic variants, as well as in the early stages of sporadic ALS, and typically precedes motor neuron involvement and overt neurodegeneration. The causes of cortical hyper-excitability are not yet fully understood but is mainly agreed to be an early event. ALS and FTD are diseases in which synaptic dysfunction is reported throughout disease onset and stages of progression. Here we review the dysfunctions of the central nervous system synapses associated with the nucleotide repeat expansion in C9ORF72 observed in patients, organismal, and cellular models of ALS and FTD.
Ozcan, K. et al. 2021. Scientific Report
The effects of molecular crowding and CpG hypermethylation on DNA G-quadruplexes formed by the C9orf72 nucleotide repeat expansion
The C9orf72 NRE forms an antiparallel DNA G-quadruplex (GQ) structure, but can transitions to a parallel GQ structure under specific molecular crowding conditions. CpG hypermethylation of the C9orf72 NRE DNA has minimal effect on the GQ distributions. Finally, in silico molecular dynamic simulations demonstrate that both methylated and nonmethylated C9orf72 NRE GQ DNA structures are hyper stable.