A5018434364- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Genetics and Neurodevelopmental Disorders
- Fungal and yeast genetics research
- Parkinson's Disease Mechanisms and Treatments
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Alzheimer's disease research and treatments
- Neurological disorders and treatments
- Glycogen Storage Diseases and Myoclonus
- RNA Research and Splicing
- Renal Diseases and Glomerulopathies
- Autoimmune Bullous Skin Diseases
- Nail Diseases and Treatments
- Antifungal resistance and susceptibility
- Cerebrovascular and genetic disorders
- Amyotrophic Lateral Sclerosis Research
- RNA regulation and disease
- Liver Diseases and Immunity
- Fungal Biology and Applications
- Colorectal Cancer Treatments and Studies
- Nuclear Physics and Applications
- Cellular transport and secretion
- Renal cell carcinoma treatment
- Dementia and Cognitive Impairment Research
- Pancreatic and Hepatic Oncology Research
Broad Institute
2023-2025
Harvard University
2023-2025
Massachusetts General Hospital
2023-2025
The University of Tokyo
1993-2023
Jichi Medical University
2022
Jichi Medical University Saitama Medical Center
2022
University of Tokyo Hospital
2018-2020
Kitasato Institute Hospital
2014
Huntington's disease, one of more than 50 inherited repeat expansion disorders1, is a dominantly neurodegenerative disease caused by CAG in HTT2. Inherited length the primary determinant age onset, with human genetic studies underscoring that driven length-dependent propensity to further expand brain3–9. Routes slowing somatic expansion, therefore, hold promise for disease-modifying therapies. Several DNA repair genes, notably mismatch pathway, modify mouse models10. To identify novel...
Abstract Huntington’s disease (HD) is a dominant neurological disorder caused by an expanded HTT exon 1 CAG repeat that lengthens huntingtin’s polyglutamine tract. Lowering mutant huntingtin has been proposed for treating HD, but genetic modifiers implicate somatic expansion as the driver of onset. We find branaplam and risdiplam, small molecule splice modulators lower promoting pseudoexon inclusion, also decrease unstable in engineered cell model. Targeted CRISPR-Cas9 editing shows this...
To report the ocular characteristics of neuronal intranuclear inclusion disease (NIID)-related retinopathy with expansion CGG repeats in NOTCH2NLC gene.Seven patients from six families (aged 66-81 years) diagnosed adult-onset NIID were studied. Ophthalmologic examinations, including best-corrected visual acuity (BCVA), Goldmann perimetry, fundus photography, autofluorescence (FAF) imaging, optical coherence tomography (OCT), and full-field electroretinography (ERGs), performed. The gene was...
CSF tau phosphorylated at threonine 181 (p-tau181) is a widely used biomarker for Alzheimer disease (AD) and has recently been regarded to reflect β-amyloid and/or p-tau deposition in the AD brain. Neuronal intranuclear inclusion (NIID) neurodegenerative characterized by inclusions neurons, glial cells, other somatic cells. Symptoms include dementia, neuropathy, others. biomarkers were not reported. The objective of this study was investigate whether including p-tau181 are altered patients...
Heterozygous CGG repeat expansions in low-density lipoprotein receptor-related protein 12 (LRP12) have recently been identified as a cause of oculopharyngodistal myopathy (OPDM), and the disease is designated OPDM type 1 (OPDM1). In contrast to broadening our knowledge on genetic background OPDM, what we know clinical phenotype genetically confirmed OPDM1 remains limited.This investigation was single-center case series study consisting ten patients from seven families. Repeat-primed...
2571 Background: P, an oral small molecule inhibitor of VEGFR-1,2,3, PDGFR-α, β, and c-Kit is FDA approved for advanced renal cancer. However the maximum tolerated dose (MTD) in Pts with varying degrees LD has not yet been determined. Because P primarily eliminated through hepatic route, we sought to determine MTD malignancies LD. Methods: malignancies, KPS ≥ 60%, adequate function, hematologic values were enrolled cohorts defined by degree LD: none (N), mild (M) (bilirubin < 1.5x ULN or ALT...
Abstract Huntington’s disease (HD) is a dominantly inherited neurodegenerative disorder whose motor, cognitive, and behavioral manifestations are caused by an expanded, somatically unstable CAG repeat in the first exon of HTT that lengthens polyglutamine tract huntingtin. Genome-wide association studies (GWAS) have revealed DNA repair genes influence age-at-onset HD implicate somatic expansion as primary driver timing. To prevent consequent neuronal damage, small molecule splice modulators...
What is known and objective Itraconazole, a CYP3A inhibitor, used for the treatment onychomycosis with three-cycle pulse therapy over 3 months, but its effects on in vivo activity during entire course remain unknown. Methods Urinary 6β-hydroxycortisol/cortisol ratios were determined 19 patients onychomycosis, before therapy, three cycles of itraconazole (200 mg twice daily week each monthly cycle) at month after completion therapy. Results discussion The mean ratio was reduced by 68% from...
Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative characterized by eosinophilic hyaline inclusions in the neurons, glial cells, and other somatic cells. Although CGG repeat expansions NOTCH2NLC have been identified most East Asian patients with NIID, pathophysiology of NIID remains unclear. Ubiquitin- p62-positive are pathological hallmark NIID. Targeted immunostaining studies several proteins present these inclusions. However, global molecular changes within nuclei...
Abstract Background and Objectives CSF tau phosphorylated at threonine 181 (p-tau181) is a widely used biomarker for Alzheimer’s disease (AD) has recently been regarded to reflect amyloid-beta (Aβ) and/or p-tau deposition in the AD brain. Although it important know how this reacts other neurocognitive diseases, p-tau181 patients with neuronal intranuclear inclusion (NIID) not studied. Methods concentrations of p-tau181, total tau, 1-42 (Aβ42), monoamine metabolites homovanillic acid (HVA),...
Abstract Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative characterized by eosinophilic hyaline inclusions in the neurons, glial cells, and other somatic cells. Although CGG repeat expansions NOTCH2NLC have been identified most East Asian patients with NIID, pathophysiology of NIID remains unclear. Intranuclear are pathological hallmark NIID. Previously, immunohistochemistry has revealed that ubiquitin-, p62-, SUMO-1-positive, suggesting possible alteration...