Ruxandra Dafinca
MSc DPhil
Senior Postdoctoral Research Fellow
Exploring dysfunctional pathways in neurons from ALS patients
My research focuses on modelling amyotrophic lateral sclerosis in neurons obtained by differentiating induced pluripotent stem cells (iPSCs) derived from patient fibroblasts.
Amyotrophic lateral sclerosis (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. The recently discovered hexanucleotide intronic GGGGCC expansion in chromosome 9 open reading frame 72 (C9orf72) establishes a firm genetic link between ALS and FTLD, being classified as the most common cause of familial and sporadic ALS and FTLD,
In our lab, we use induced pluripotent stem cells (iPSCs) from the fibroblasts of ALS patients and differentiate them to motor neurons for functional investigations. The neurons obtained by iPSCs derivation have the advantage of carrying disease-specific genetic profiles and display characteristic neurodegenerative traits.
Previously, I investigated the phenotypes of motor neurons derived from ALS patients by looking at differences in nucleocytoplasmic transport and mitochondrial deficits. I have also used CRISPR/Cas9 genome engineering to correct the mutations in these patient lines.
With a Brain Science Fellowship, I am establishing a programme of research investigating the pathways that induce dysfunctional synaptic transmission in ALS/FTD neurons from patients.
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), Nature Communications, 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), Scientific Reports, 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), Frontiers in Cellular Neuroscience, 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), Neurobiology of Disease, 144, 105050 - 105050
Research groups
Collaborators
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Kevin Talbot
Head of Department and Professor of Motor Neuron Biology
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Alexander Thompson
MRC Clinician Scientist and Lady Edith Wolfson Fellow
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Martin Turner
Professor of Clinical Neurology & Neuroscience