Frances M. Platt

Lysosomal signaling pathways influence heart rhythm, and regulate atrial function

This study investigates the role of lysosomal Ca2+ signaling in heart rhythm and atrial function, finding that NAADP pathway inhibition affects SAN pacemaker activity and cAMP production in atrial myocytes.

Mice with mono-allelic p.R37H Dhdds variant show aberrant glycosylation and interneuron deficits

This study describes a mouse model of DHDDS-CDG, showing seizures, myoclonus, and cognitive deficits linked to glycosylation defects and interneuron abnormalities.

A novel pipeline for the validation of manganese chelators for the treatment of manganese overload

This paper develops a pipeline to identify and evaluate novel manganese chelators using zebrafish and mouse models, finding that H3PyC3A and Me3PyC3A show improved manganese mobilization and reduced accumulation.

Molecular and Structural Basis of Cardiac Remodelling in Niemann-Pick Type C

This study identifies cardiac involvement in Niemann-Pick type C through ECG abnormalities, fibrosis, and transcriptomic changes in patients and Npc1-/- mice.

HKDC1 contributes to aberrant lysosome-mitochondria contact in Niemann-Pick disease type C

This study establishes isogenic NPC1 and NPC2 models to reveal that HKDC1 regulates mitochondrial-lysosome contact in NPC1-deficient cells.

GPNMB and glycosphingolipid measurements in cerebrospinal fluid and plasma from Parkinson's disease patients

The paper measures GPNMB and glycosphingolipid levels in CSF and plasma from PD patients and controls, finding sex-based differences and associations with PD biomarkers.

Sialylated Gangliosides are Required for Plasma Membrane Organization and Neuronal Function

The paper shows that sialylated gangliosides are essential for plasma membrane organization and neuronal function, with ST3GAL5 deficiency causing severe disruptions in glycosphingolipid composition and neuronal activity.

N-acetyl-L-leucine (Levacetylleucine) normalizes Transcription Factor EB (TFEB) activity by stereospecific bidirectional modulation

This paper demonstrates that levacetylleucine modulates TFEB activity in a bidirectional manner, normalizing lysosomal function in both wild-type and NPC1 knockout cells.

Alternative Splicing Directs PMCA2 to Lysosomes and is Linked to Neurodegeneration

The paper identifies a splice variant-dependent localization of PMCA2 to lysosomes and links it to neurodegenerative diseases.

Stereospecific rapid activation of Transcription Factor EB (TFEB) by Levacetylleucine (NALL)

This paper shows that NALL activates TFEB, enhancing lysosomal and autophagic function, which may explain its therapeutic effects in neurodegenerative diseases.

N-Acetyl-l-Leucine (NALL) rescues inter-organelle communication in Niemann-Pick disease type-C patient cells.

The paper shows NALL rescues inter-organelle communication and restores lysosomal and mitochondrial function in NPC patient cells.

Plasma Membrane Remodelling in GM2 Gangliosidoses Drives Synaptic Dysfunction

This study develops i3Neuron models of Tay-Sachs and Sandhoff diseases, revealing plasma membrane remodeling and synaptic dysfunction due to GM2 ganglioside accumulation.

The annotation and function of the Parkinson's and Gaucher disease-linked gene GBA1 has been concealed by its protein-coding pseudogene GBAP1

The paper shows that sequencing ambiguity between GBA1 and its pseudogene GBAP1 affects transcriptomic analysis, revealing non-lysosomal functions in the brain and widespread annotation inaccuracies.

Compartmentalisation proteomics revealed endolysosomal protein network changes in a goat model of atrial fibrillation

The paper uses proteomics and other methods to study endolysosomal changes in a goat model of atrial fibrillation, identifying upregulated pathways and specific proteins.

Cardiac Atrial Compartmentalisation Proteomics: A Modified Density Gradient Method to Analyse Endo-lysosomal Proteins

The paper presents a modified density gradient method for isolating endo-lysosomal proteins from cardiac tissue and reports proteomic analysis of these fractions in guinea pigs.

Acetyl-Leucine slows disease progression in lysosomal storage disorders

This study shows that ADLL and its enantiomer ALL slow disease progression in lysosomal storage disorders through mechanisms involving glucose and antioxidant metabolism.