Ruxandra Dafinca
MSc DPhil
Brain Science Research Fellow
Exploring dysfunctional pathways in neurons from ALS patients
Research summary
I am leading a programme of research investigating synaptic deficiencies in amyotrophic lateral sclerosis (ALS) in neurons derived from patient induced pluripotent stem cells (iPSCs).
ALS is a progressive and fatal adult-onset motor neuron disorder characterized by the degeneration of motor neurons in the brain and spinal cord, leading to death within 3-5 years. A hexanucleotide intronic GGGGCC expansion in chromosome 9 open reading frame 72 (C9orf72) establishes a firm genetic link between ALS and frontotemporal dementia (FTD), being classified as the most common cause of familial and sporadic ALS/FTD.
In 2013, I have developed and implemented in our laboratory the differentiation of iPSCs from ALS/FTD patients to motor and cortical neurons in a dish. Using iPSC-neurons, I aim to determine regulatory pathways affected by disease by implementing the use of spatial proteomics combined with transcriptomics and live imaging. The overarching goal of my work is to identify new therapeutic targets that can inform drug development for ALS/FTD.
If you are interested in joining the group or would like to discuss a collaboration, please contact me.
Recent publications
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Mutant GGGGCC RNA prevents YY1 from binding to Fuzzy promoter which stimulates Wnt/β-catenin pathway in C9ALS/FTD.
Journal article
Chen ZS. et al, (2023), Nat Commun, 14
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C9orf72-ALS human iPSC microglia are pro-inflammatory and toxic to co-cultured motor neurons via MMP9.
Journal article
Vahsen BF. et al, (2023), Nat Commun, 14
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Poly(ADP-ribose) promotes toxicity of C9ORF72 arginine-rich dipeptide repeat proteins.
Journal article
Gao J. et al, (2022), Sci Transl Med, 14
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Human iPSC co-culture model to investigate the interaction between microglia and motor neurons.
Journal article
Vahsen BF. et al, (2022), Sci Rep, 12
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Human stem cell models of neurodegeneration: From basic science of amyotrophic lateral sclerosis to clinical translation.
Journal article
Giacomelli E. et al, (2022), Cell Stem Cell, 29, 11 - 35
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Axonal TDP-43 condensates drive neuromuscular junction disruption through inhibition of local synthesis of nuclear encoded mitochondrial proteins.
Journal article
Altman T. et al, (2021), Nat Commun, 12
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The Role of Mitochondrial Dysfunction and ER Stress in TDP-43 and C9ORF72 ALS.
Journal article
Dafinca R. et al, (2021), Front Cell Neurosci, 15
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An ALS-linked mutation in TDP-43 disrupts normal protein interactions in the motor neuron response to oxidative stress.
Journal article
Feneberg E. et al, (2020), Neurobiol Dis, 144