Explanipedia

Validation of a comprehensive long-read sequencing platform for broad clinical genetic diagnosis Open

Siddhartha Sen, Hillary P. Handler, Alec Victorsen, Zach Flaten, Aidan Ellison , et al. · 2025

Though short read high-throughput sequencing, commonly known as Next-Generation Sequencing (NGS), has revolutionized genomics and genetic testing, there is no single genetic test that can accurately detect single nucleotide variants (SNVs)…

Increased intrinsic membrane excitability is associated with olivary hypertrophy in spinocerebellar ataxia type 1 Open

Logan M Morrison, Haoran Huang, Hillary P. Handler, Min Fu, Deborah M. Jones , et al. · 2024

One of the characteristic regions of brainstem degeneration across multiple spinocerebellar ataxias (SCAs) is the inferior olive (IO), a medullary nucleus that plays a key role in motor learning. The vulnerability of IO neurons remains a p…

Mapping SCA1 regional vulnerabilities reveals neural and skeletal muscle contributions to disease Open

Lisa Duvick, William M. Southern, Kellie Benzow, Zoe N. Burch, Hillary P. Handler , et al. · 2024

Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by an expanded polyglutamine tract in the widely expressed ataxin-1 (ATXN1) protein. To elucidate anatomical regions and cell types that underlie mutant ATXN1…

P209: Development of a single comprehensive genomic test based on long-read sequencing technology for the diagnosis of rare genetic disorders Open

Siddhartha Sen, Hillary P. Handler, Matthew Bower, Alec Victorsen, Zach Flaten , et al. · 2024

Though traditional short read Next Generation Sequencing (NGS) has revolutionized genomics and genetic testing, there is no single genetic test that can accurately evaluate the full spectrum of complex structural variants (SV) and repetiti…

60 Impact of Reducing the Nuclear Mutant ATXN1 on Spinocerebellar Ataxia-Like Phenotype Open

Kathleen B. Mather, Lisa Duvick, Hillary P. Handler, Harry T. Orr · 2023

Objective: Spinocerebellar ataxia type one (SCA1) is an autosomal dominant neurodegenerative disease caused by an expanded CAG repeat that encodes glutamine (polyQ) in the affected ATXN1 gene. SCA1 pathology is commonly characterized by th…

Increased intrinsic membrane excitability is associated with hypertrophic olivary degeneration in spinocerebellar ataxia type 1 Open

Logan M Morrison, Haoran Huang, Hillary P. Handler, Min Fu, David D. Bushart , et al. · 2023

One of the characteristic areas of brainstem degeneration across multiple spinocerebellar ataxias (SCAs) is the inferior olive (IO), a medullary nucleus that plays a key role in motor learning. In addition to its vulnerability in SCAs, the…

Disruption of the ATXN1-CIC complex reveals the role of additional nuclear ATXN1 interactors in spinocerebellar ataxia type 1 Open

Stephanie L. Coffin, Mark A. Durham, Larissa Nitschke, Eder Xhako, Amanda M. Brown , et al. · 2023

(Neuron 111, 481–492.e1–e8; February 15, 2023) In the originally published paper, there was one error in the STAR Methods section “Generation of Atxn1154Q[V591A;S602D]/2Q and Atxn12Q[V591A;S602D]/2Q mouse models.” When describing the mouse…

Delineating regional vulnerability in the neurodegenerative disease SCA1 using a conditional mutant ATXN1 mouse Open

Lisa Duvick, William M. Southern, Kellie Benzow, Zoe N. Burch, Hillary P. Handler , et al. · 2023

Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by an expanded polyglutamine tract in the widely expressed ATXN1 protein. To elucidate anatomical regions and cell types that underlie mutant ATXN1-induced di…

BDNF is altered in a brain-region specific manner and rescues deficits in Spinocerebellar Ataxia Type 1 Open

Juao-Guilherme Rosa, Katherine Hamel, Alyssa Soles, Carrie Sheeler, Ella Borgenheimer , et al. · 2023

Spinocerebellar ataxia type 1 (SCA1) is an adult-onset, dominantly inherited neurodegenerative disease caused by the expanded polyQ tract in the protein ATAXIN1 (ATXN1) and characterized by progressive motor and cognitive impairments. Ther…

Disruption of the ATXN1-CIC complex reveals the role of additional nuclear ATXN1 interactors in spinocerebellar ataxia type 1 Open

Stephanie L. Coffin, Mark A. Durham, Larissa Nitschke, Eder Xhako, Amanda M. Brown , et al. · 2022

Decreasing mutant ATXN1 nuclear localization improves a spectrum of SCA1-like phenotypes and brain region transcriptomic profiles Open

Hillary P. Handler, Lisa Duvick, Jason S. Mitchell, Marija Cvetanović, Molly Reighard , et al. · 2022

Spatial and Temporal Diversity of Astrocyte Phenotypes in Spinocerebellar Ataxia Type 1 Mice Open

Juao-Guilherme Rosa, Katherine Hamel, Carrie Sheeler, Ella Borgenheimer, Stephen Gilliat , et al. · 2022

While astrocyte heterogeneity is an important feature of the healthy brain, less is understood about spatiotemporal heterogeneity of astrocytes in brain disease. Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disea…

Disrupting ATXN1 Nuclear Localization in a Knock-in SCA1 Mouse Model Improves a Spectrum of SCA1-Like Phenotypes and their Brain Region Associated Transcriptomic Profiles Open

Hillary P. Handler, Lisa Duvick, Jason S. Mitchell, Marija Cvetanović, Molly Reighard , et al. · 2021

SUMMARY Spinocerebellar ataxia type 1 (SCA1) is a dominant trinucleotide repeat neurodegenerative disease characterized by motor dysfunction, cognitive impairment, and premature death. Degeneration of cerebellar Purkinje cells is a frequen…

Spatial and temporal diversity of astrocyte phenotypes in Spinocerebellar ataxia type 1 mice Open

Juao-Guilherme Rosa, Katherine Hamel, Carrie Sheeler, Ella Borgenheimer, Stephen Gilliat , et al. · 2021

While astrocyte heterogeneity is an important feature of the healthy brain, less is understood about spatiotemporal heterogeneity of astrocytes in brain disease. Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disea…

Altered Capicua expression drives regional Purkinje neuron vulnerability through ion channel gene dysregulation in spinocerebellar ataxia type 1 Open

Ravi Chopra, David D. Bushart, John P Cooper, Dhananjay Yellajoshyula, Logan M Morrison , et al. · 2020

Selective neuronal vulnerability in neurodegenerative disease is poorly understood. Using the ATXN1[82Q] model of spinocerebellar ataxia type 1 (SCA1), we explored the hypothesis that regional differences in Purkinje neuron degeneration co…

Antisense Oligonucleotide Therapeutic Approach for Suppression of Ataxin-1 Expression: A Safety Assessment Open

Brennon O’Callaghan, Bente Hofstra, Hillary P. Handler, Holly Kordasiewicz, Tracy Cole , et al. · 2020

Spinocerebellar ataxia type 1 (SCA1) is a lethal, autosomal dominant neurodegenerative disease caused by a polyglutamine expansion in the ATAXIN-1 (ATXN1) protein. Preclinical studies demonstrate the therapeutic efficacy of approaches that…

Antisense oligonucleotide–mediated ataxin-1 reduction prolongs survival in SCA1 mice and reveals disease-associated transcriptome profiles Open

Jillian Friedrich, Holly Kordasiewicz, Brennon O’Callaghan, Hillary P. Handler, Carmen Wagener , et al. · 2018

Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited ataxia caused by expansion of a translated CAG repeat encoding a glutamine tract in the ataxin-1 (ATXN1) protein. Despite advances in understanding the pathogenesis of SCA1, th…

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