A5034955101- Genetic Neurodegenerative Diseases
- Neurofibromatosis and Schwannoma Cases
- Fungal and yeast genetics research
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- Neuroblastoma Research and Treatments
- DNA Repair Mechanisms
- Sarcoma Diagnosis and Treatment
- Ocular Oncology and Treatments
- Neuroendocrine Tumor Research Advances
- Meningioma and schwannoma management
Massachusetts General Hospital
1987-2024
Harvard University
1987-2023
Louisiana State University Health Sciences Center New Orleans
2020-2021
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...
Somatic expansion of the CAG repeat tract that causes Huntington's disease (HD) is thought to contribute rate pathogenesis. Therefore, factors influencing are potential therapeutic targets. Genes in DNA mismatch repair pathway critical drivers somatic HD mouse models. Here, we have tested, using genetic and pharmacological approaches, role endonuclease domain protein MLH3 mice patient cells. A point mutation completely eliminated brain peripheral tissues a knock-in model (HttQ111). To test...
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...
We have used DNA linkage analysis in 11 families with Von Recklinghausen neurofibromatosis (VRNF) order to search for the chromosomal localisation of defective gene causing this serious neurological disorder. Three groups polymorphic markers were used: (1) chromosome 22, because possible allelic genetic heterogeneity between VRNF and bilateral acoustic neurofibromatosis; (2) near centromere 4, since there was preliminary evidence Gc; (3) oncogenes growth factors as candidate genes VRNF. Our...
Abstract Somatic expansion of the CAG repeat tract that causes Huntington’s disease (HD) is thought to contribute rate pathogenesis. Therefore, factors influencing are potential therapeutic targets. Genes in DNA mismatch repair pathway critical drivers somatic HD mouse models. Here, we have tested, using genetic and pharmacological approaches, role endonuclease domain protein MLH3 mice patient cells. A point mutation completely eliminated brain peripheral tissues a knock-in model ( Htt Q111...