Siddharthan Chandran

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.

The paper uses polygenic risk scores to analyze genetic contributions to neurodegenerative diseases across brain cell types, finding shared and disease-specific genetic risks.

This paper identifies FABP8/PMP2 as a defining feature of human and old-world monkey CNS myelin, revealing molecular heterogeneity in myelin sheaths and its role in cholesterol enrichment.

This study shows that mislocalisation of TDP-43 to the cytoplasm in neurons or oligodendrocytes causes axonopathy and dysmyelination, highlighting the role of cell-type-specific loss of function in neurodegeneration.

This study shows how electrical stimulation affects spiking responses in human cortical organoids, finding parameter-dependent excitatory and inhibitory responses with local circuit contributions.

The paper tests for axon initial segment (AIS) structural plasticity in human, mouse, and rat cortical neurons across different conditions and finds no evidence of AIS length changes over short-term activity modulation.

This study shows that C9ORF72-mutant astrocytes disrupt axonal transport in motor neurons, and correcting this rescues transport deficits.

This study investigates the role of FMRP in oligodendrocyte maturation and myelination in human and rat models, finding shared defects in morphology and function.

This study shows that FMRP loss in microglia increases RAC1 signaling, leading to inflammation and neuronal hyperexcitability in FXS, which can be mitigated by RAC1 inhibition.

The paper introduces a method to compress genetic data using autoencoders that leverage linkage disequilibrium structure, achieving high reconstruction accuracy while reducing data size.

The paper shows TSPO expression increases in activated microglia in rodent models but not in human neurodegenerative diseases, indicating species-specific differences in TSPO function.

The paper shows that astrocyte-oligodendrocyte interaction is critical for remyelination and identifies a drug strategy targeting this interaction to promote central nervous system regeneration.

This study shows that C9orf72 mutations disrupt autophagy in microglia, leading to immune dysfunction and increased motor neuron death in ALS/FTD.

The paper compares human and mouse exon usage in cortical neurons, finding conservation in basal inclusion but divergence in activity-dependent usage, suggesting both cis-acting and trans-acting factors contribute to species differences.

The paper assesses axonal mitochondrial content and complex IV activity in multiple experimental disease models of MS, finding that increased mitochondrial content does not always correlate with increased COX activity, and that COX activity inversely correlates with axonal injury.

The paper uses random forest modelling to identify microglial activation as a key classifier for C9orf72-related ALS and shows spatial FUS staining changes predict disease status.

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

The paper identifies a conserved myelination mechanism in oligodendrocytes that forms paranodal bridges, enabling extended myelin sheaths along axons, which degenerate more frequently with age.

This study shows reducing Kv3.4 levels in a mouse model of Alzheimer's disease reduces synapse loss and changes in spine morphology.

This study shows that INPP5E negatively regulates Sonic Hedgehog signaling in human cortical organoids, promoting dorsal telencephalic identity and preventing ventralization.

This study shows that C9orf72 repeat expansions produce toxic arginine-rich DPRs that disrupt axonal transport by interacting with microtubules and motor proteins, contributing to ALS/FTD.

This study compares vitamin D levels between people with multiple sclerosis and controls in the UK using remote sampling, finding higher levels in MS patients due to supplementation.

The DPUK Data Portal provides secure access to cohort data for dementia research, supporting multi-modal analyses and collaborations across multiple institutions.

The paper uses unsupervised machine learning to identify three molecular subtypes in ALS cortex samples, associated with oxidative stress, retrotransposon activation, and glial activation.

The paper investigates the impact of a t(1;11) translocation on white matter integrity and oligodendrocyte-myelin function using DTI and cellular models.

This study shows that a DISC1 mutation linked to mental illness disrupts NMDAR dynamics and synaptic function in neurons, affecting excitatory synapses and vesicle dynamics.