Michael R. Hayden

Proteomic profiling of baseline CSF and serum from HDClarity identifies signatures for Huntington disease staging and stratification

This study identifies proteomic signatures in CSF and serum from HDClarity that can stage and stratify Huntington disease across clinical stages with high accuracy.

Synonymous HTT CAA/CCA-loss variants associated with early Huntington disease onset enhance toxicity beyond somatic instability

This study shows that HTT CAA/CCA-loss variants increase toxicity in Huntington disease models independently of somatic repeat instability.

Treatment of Huntington's disease with a pan-HTT-targeting CRISPR nuclease

This study develops a CRISPR-Cas9 system targeting all HTT alleles in HD mouse models, reducing mutant HTT and improving disease symptoms.

Loss of interruption in the HTT CAG repeat is associated with increased somatic expansion and loss of medium spiny neurons in HD

The paper shows that loss of interruption in HTT CAG repeats increases somatic expansion and MSN loss in HD, with greater effects in patients with CAG-CCG LOI.

Challenges and advances for huntingtin detection in cerebrospinal fluid: in support of relative quantification

This study investigates challenges in mHTT quantification in CSF, showing that absolute quantitation is unreliable due to protein complexity and recommends relative quantitation instead.

Early Neurodevelopmental Defects in Huntingtons Disease are Driven by Choroid Plexus Overgrowth and Altered Paracrine Signaling

This study identifies early neurodevelopmental defects in juvenile-onset HD driven by choroid plexus overgrowth and altered paracrine signaling using organoid and mouse models.

Reduced S-acylation of SQSTM1/p62 in Huntington disease is associated with impaired autophagy

The paper shows reduced S-acylation of SQSTM1/p62 in Huntington disease impairs autophagy by blocking autophagic flux and causing empty autophagosomes.

Huntingtin expression influences spontaneous seizure disorder susceptibility in FVN/B mice

This study shows that altering huntingtin levels affects seizure susceptibility in FVB/N mice, with over-expression preventing seizures and reduction increasing their frequency.

Mitochondrial and redox modifications in early stages of Huntington disease

This study investigates mitochondrial dysfunction and redox changes in early Huntington disease stages using human and mouse models, showing increased mitochondrial activity and altered morphology.

Rescue of aberrant huntingtin palmitoylation ameliorates mutant huntingtin-induced toxicity

This study investigates the role of HTT palmitoylation in Huntington disease by assessing its dysregulation in models and showing that modulating palmitoylation reduces mHTT toxicity.

Coupled Control of Distal Axon Integrity and Somal Responses to Axonal Damage by the Palmitoyl Acyltransferase ZDHHC17

This study shows that ZDHHC17 couples DLK and NMNAT2 pathways to control both somal and distal axon degeneration after optic nerve crush.

The interaction of aging and oxidative stress contributes to pathogenesis in mouse and human Huntington disease neurons

This study investigates how aging and oxidative stress interact in Huntington disease neurons from mice and humans, finding that aging accelerates mutant HTT accumulation and increases oxidative stress sensitivity.

Gene expression profiles complement the analysis of genomic modifiers of the clinical onset of Huntington disease

The paper identifies novel modifier genes for Huntington disease by combining population-scale gene expression data with patient genomic data.

Spontaneous Axonal ER Ca2+ Waves Mediate a Shift From Action Potential-Dependent to Independent Glutamate Release in the YAC128 HD-Model

The paper shows that spontaneous axonal ER Ca2+ waves increase miniature glutamate release while reducing AP-dependent release in YAC128 HD-model neurons.

Length of uninterrupted CAG repeats, independent of polyglutamine size, results in increased somatic instability and hastened age of onset in Huntington disease

This study identifies a genetic variant that reduces interruption between CAG and CCG repeats in the HTT gene, leading to earlier onset of Huntington disease and increased somatic instability.

Identification of a novel caspase cleavage site in huntingtin that regulates mutant huntingtin clearance.

The paper identifies a new caspase-1 cleavage site in mutant huntingtin that promotes its clearance and reduces aggregation.

A human huntingtin SNP alters post-translational modification and pathogenic proteolysis of the protein causing Huntington disease

The paper identifies a human SNP that modifies post-translational myristoylation of huntingtin, altering its proteolysis and contributing to Huntington disease pathogenesis.

Feeding Schedule And Proteolysis Regulate Autophagic Clearance Of Mutant Huntingtin

This study shows that scheduled feeding and prevention of caspase-6 cleavage enhance autophagic clearance of mutant huntingtin in HD models and patients.