Pietro Fratta

Exploring transcriptomic and genomic latent variable correction approaches in differential expression analysis.

This paper evaluates combining expression-based surrogate variables and genotype-based principal components in differential expression analysis, finding the combined approach improves replicability and biological recall in ALS datasets.

Monomeric TDP-43 binds GU-rich RNA via its NTD but only its oligomers block cryptic exon inclusion

This study shows that the NTD of TDP-43 binds UG-rich RNA on monomers, while oligomerization is essential for repressing cryptic exons.

Refining gene delivery to skeletal muscle with a dual-strategy approach of muscle-tropic AAV capsids and muscle-specific promoters.

The paper investigates a dual-strategy approach using a muscle-tropic AAV capsid and muscle-specific promoter to improve gene delivery efficiency and reduce off-target expression in skeletal muscle.

TDP-43 dysfunction induces cryptic circular RNAs in ALS/FTD

This study identifies TDP-43 dysfunction as a cause of cryptic circular RNA formation in ALS/FTD, showing their association with disease-relevant protein loss and potential as biomarkers.

Brain-derived neurotrophic factor amplifies neuron-intrinsic programs to enhance axonal regeneration in human motor neurons

This study shows BDNF enhances axonal regeneration in human motor neurons by regulating RNA metabolism and cytoskeletal dynamics through kinase pathways.

TBK1 activity regulates the directionality of axonal transport of signalling endosomes

The paper shows TBK1 phosphorylates Rab7 to regulate unidirectional retrograde transport of signalling endosomes in motor neurons, linking TBK1 dysfunction to ALS-related transport impairments.

Lysosomal escape and TMEM106B fibrillar core determine TDP-43 seeding outcomes

The paper investigates factors determining TDP-43 seeding outcomes in FTLD-TDP, identifying TMEM106B fibrillar core and lysosomal escape as critical drivers.

U7 small nuclear RNA splice-switching therapeutics for STMN2 and UNC13A in Amyotrophic Lateral Sclerosis

The paper develops U7 snRNA therapeutics to correct TDP-43-dependent mis-splicing in ALS, restoring gene expression and neuronal function in human iPSC-derived neurons.

Sensitivity to TDP-43 loss and degradation resistance determine cryptic exon biomarker potential

The paper identifies cryptic splicing events (CEs) sensitive to TDP-43 loss and develops a composite score to detect TDP-43 pathology across tissues.

CANVAS causing AAGGG repeat expansions cause tissue-specific reduction in RFC1 expression and increase sensitivity to DNA damage

Integrative multiomic analysis links TDP-43-driven splicing defects to cascading proteomic disruption of ALS/FTD pathways

The paper identifies TDP-43-dependent molecular cascades in ALS/FTD by integrating multiomic data from iPSC-derived neurons and validates key genes through experimental assays.

TDP-43 pathology triggers SRRM4-dependent cryptic splicing of G3BP1 in ALS/FTD

The paper shows that TDP-43 pathology causes a cryptic exon in G3BP1 to be included in neurons, leading to a protein that disrupts stress granule dynamics in ALS/FTD.

TDP-43 pathology induces CD8+ T cell activation through cryptic epitope recognition

This study identifies cryptic epitopes from de novo proteins caused by TDP-43 pathology as targets of CD8+ T cell activation in ALS and IBM.

Innervation and cargo-specific axonal transport impairments in FUS-ALS mice with gain and loss of function

This study identifies sex-dependent motor neuron dysfunction and cargo-specific axonal transport impairments in FUS-ALS mice, linking endosomal transport defects to denervation in ALS.

C9orf72 polyGA knock-in mice exhibit mild motor and proteomic changes consistent with ALS/FTD

This study creates (GA)400 knock-in mice to model C9orf72 polyGA expression, finding mild motor dysfunction and proteomic changes in the spinal cord.

ProtPipe: A Multifunctional Data Analysis Pipeline for Proteomics and Peptidomics

ProtPipe is a data analysis pipeline for proteomics and peptidomics that automates processing, quality control, and downstream analysis of mass spectrometry data.

Creation of de novo cryptic splicing for ALS/FTD precision medicine

The paper develops TDP-REG, a system using cryptic splicing to enable precise gene therapy activation in diseased neurons for ALS/FTD.

Increased frequency of repeat expansion mutations across different populations

The paper estimates the frequency of repeat expansion mutations across populations using whole genome sequencing data and finds higher expected prevalence than current reports.

Altered mRNA transport and local translation in iNeurons with RNA binding protein knockdown

This study investigates how knocking down RNA binding proteins affects mRNA transport and local translation in neurons, revealing distinct impacts on neuritic proteome and transcriptome.

Loss of TDP-43 induces synaptic dysfunction that is rescued by UNC13A splice-switching ASOs

This study shows that loss of TDP-43 causes synaptic dysfunction through a cryptic exon in UNC13A, which is rescued by antisense oligonucleotides.

Mis-spliced transcripts generate de novo proteins in TDP-43-related ALS/FTD

The paper shows that loss of TDP-43 function leads to the expression of de novo proteins from mis-spliced mRNA transcripts in ALS/FTD.

A functional interaction between TDP-43 and USP10 reveals USP10 dysfunction in TDP-43 proteinopathies

This study identifies a functional interaction between TDP-43 and USP10, showing USP10 modulates alternative splicing and can reduce TDP-43 toxicity in a mouse model of ALS and FTD.

TDP-43 loss induces extensive cryptic polyadenylation in ALS/FTD

The paper identifies novel cryptic polyadenylation events induced by TDP-43 loss in ALS/FTD using bioinformatic methods and shows their potential disease relevance and impact on protein translation.

RNA aptamer reveals nuclear TDP-43 pathology is an early aggregation event that coincides with STMN-2 cryptic splicing and precedes clinical manifestation in ALS

This study uses an RNA aptamer to detect TDP-43 aggregation and shows that nuclear TDP-43 pathology and STMN-2 cryptic splicing occur before clinical symptoms in ALS.

PolyGR and polyPR knock-in mice reveal a conserved neuroprotective extracellular matrix signature in C9orf72 ALS/FTD neurons

The paper generates C9orf72 DPR knock-in mice and identifies an extracellular matrix signature in C9ALS/FTD that is conserved across species and protected by TGF-β1 and COL6A1.

Cell environment shapes TDP-43 function: implications in neuronal and muscle disease

The paper compares TDP-43's transcriptional and splicing effects in muscle and neuronal cells, showing tissue-specific roles in disease.

Circulating miR-181 is a prognostic biomarker for amyotrophic lateral sclerosis

The paper identifies miR-181 as a prognostic biomarker in ALS, showing it predicts higher mortality risk and improves prognosis prediction when combined with NfL.

FUS-ALS mutants alter FMRP phase separation equilibrium and impair protein translation

This study shows that FUS-ALS mutants form cytoplasmic condensates that alter FMRP phase separation, leading to translation inhibition in motor neurons.

NMJ-Analyser: high-throughput morphological screening of neuromuscular junctions identifies subtle changes in mouse neuromuscular disease models

NMJ-Analyser quantifies neuromuscular junction morphology and innervation status in mouse models, identifying structural changes in ALS and peripheral neuropathy with high accuracy.

Common ALS/FTD risk variants in UNC13A exacerbate its cryptic splicing and loss upon TDP-43 mislocalization

The paper shows that ALS/FTD risk variants in UNC13A increase sensitivity to TDP-43 depletion by promoting cryptic exon inclusion and protein loss.