A5087885035- Neurofibromatosis and Schwannoma Cases
- Sarcoma Diagnosis and Treatment
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- DNA Repair Mechanisms
- RNA modifications and cancer
- Ear and Head Tumors
- RNA and protein synthesis mechanisms
- Chromatin Remodeling and Cancer
- Congenital Heart Disease Studies
- Neuroblastoma Research and Treatments
- Congenital heart defects research
- Multiple Myeloma Research and Treatments
- Soft tissue tumor case studies
- Soft tissue tumors and treatment
- Plant Molecular Biology Research
- Genetic Mapping and Diversity in Plants and Animals
- CRISPR and Genetic Engineering
- Teratomas and Epidermoid Cysts
- Neuroscience and Neuropharmacology Research
- Esophageal and GI Pathology
- Renal and related cancers
- Plant Genetic and Mutation Studies
- T-cell and B-cell Immunology
The University of Texas MD Anderson Cancer Center
2008-2024
University of Alabama at Birmingham
2015-2016
The University of Texas at Austin
2009-2014
The University of Texas Health Science Center at Houston
2013-2014
<h3>Importance</h3> Neurofibromatosis type 1 (NF1) is a complex genetic disorder that associated with not only neurofibromas, but also an increased susceptibility to other neoplasms. <h3>Objective</h3> To evaluate the prevalence of neoplasia and outcomes among patients NF1. <h3>Design, Setting, Participants</h3> This cohort study was conducted NF1 at single academic cancer center from 1985 2020 median (range) follow-up 2.9 years (36 days 30.5 years). Of 2427 evaluated for NF1, 1607 who met...
Friedreich's ataxia (FRDA) is an autosomal recessive neurological disease caused by expansions of guanine-adenine-adenine (GAA) repeats in intron 1 the frataxin (FXN) gene. The expansion results significantly decreased expression. We report that human FRDA cells can be corrected zinc finger nuclease-mediated excision expanded GAA repeats. Editing a single allele created heterozygous, carrier-like and increased This correction persisted during reprogramming nuclease-edited fibroblasts to...
Friedreich's ataxia (FRDA) is a severe neurodegenerative disease caused by homozygous expansion of the guanine-adenine-adenine (GAA) repeats in intron 1 FXN gene leading to transcriptional repression frataxin expression. Post-translational histone modifications that typify heterochromatin are enriched vicinity repeats, whereas active chromatin marks this region underrepresented FRDA samples. Yet, immediate effect expanded on transcription progression through and their long-range surrounding...
Friedreich's ataxia (FRDA) is caused by the expansion of GAA repeats located in Frataxin (FXN) gene. The continue to expand FRDA patients, aggravating symptoms and contributing disease progression. mechanism leading repeat decreased FXN transcription remains unclear. Using single-molecule analysis replicated DNA, we detected that expanded present a substantial obstacle for replication machinery at locus cells. Furthermore, aberrant origin activation lack proper stress response rescue stalled...
Conotruncal and related heart defects (CTDs) are a group of serious relatively common birth defects. Although both maternal inherited genotypes thought to play role in the etiology CTDs, few specific genetic risk factors have been identified. To determine whether variants acting through genotype mother (e.g. via an utero effect) or case associated with we conducted genome-wide association study 750 CTD case-parent triads, follow-up analyses 358 independent triads. Log-linear were used assess...
Congenital left-sided lesions (LSLs) are serious, heritable malformations of the heart. However, little is known about genetic causes LSLs. This study was undertaken to identify common variants acting through genotype affected individual (i.e. case) or mother (e.g. via an in utero effect) that influence risk A genome-wide association (GWAS) performed using data from 377 LSL case-parent triads, with follow-up studies independent sample 224 triads and analysis combined data. Associations both...
Friedreich's ataxia (FRDA) represents a rare neurodegenerative disease caused by expansion of GAA trinucleotide repeats in the first intron FXN gene. The number FRDA patients varies from approximately 60 to <1000 and is tightly correlated with age onset severity symptoms. heterogeneity stresses need for large cohort patient samples conduct studies addressing mechanism pathogenesis or evaluate novel therapeutic candidates. Herein, we report establishment characterization an fibroblast...
Undifferentiated pleomorphic sarcomas (UPSs) are aggressive mesenchymal malignancies with no definitive cell of origin or specific recurrent genetic hallmarks. These tumors largely chemoresistant; thus, identification potential therapeutic targets is necessary to improve patient outcome. Previous studies demonstrated that high expression activated protein kinase B (AKT) in patients UPS corresponds poor disease-specific survival. Here, we demonstrate inhibiting...
BACKGROUND Based on studies in animals and humans, PAX3 T ( brachyury ) are candidate genes for spina bifida. However, neither gene has been definitively identified as a risk factor this condition. METHODS Sanger sequencing was used to identify variants all exons promoter regions 114 bifida cases. For known variants, allele frequencies cases were compared with those from public databases using unadjusted odds ratios. Novel genotyped parents assessed predicted functional impact. RESULTS We...
Objective Friedreich's ataxia (FRDA) is an autosomal recessive trinucleotide repeat expansion disorder caused by epigenetic silencing of the frataxin gene (FXN). Current research suggests that damage and variation mitochondrial DNA (mtDNA) contribute to molecular pathogenesis FRDA. We sought establish extent mutation burden across genome in FRDA cells investigate mechanisms connecting FXN downregulation acquisition mtDNA damage. Methods Damage load a panel control fibroblasts were determined...
Abstract Introduction: Neurofibromatosis Type 1 (NF-1) associated malignant peripheral nerve sheath tumors (MPNST) harbor mutations in the polycomb repressive complex 2 (PRC2) 70% of tumors. PRC2 loss results epigenetic changes, which increase histone acetylation and make DNA vulnerable to binding by bromodomain proteins. This interaction could be targeted uncouple from transcription using extra terminal inhibitors (BETi). As radiation therapy (RT) is a cornerstone MPNST treatment, we...
ABSTRACT Malignant peripheral nerve sheath tumor (MPNST) development is characterized by an altered DNA methylation landscape, which presents a promising area for developing MPNST‐specific biomarkers screening patients with NF1. Genome‐wide profiling of cohort 13 MPNST (29 samples and adjacent neurofibroma tissues) NF1‐MPNST cell lines was performed to identify validate candidate CpG sites (CpGs). A logistic regression prediction model constructed select CpGs distinct from neurofibromas...
Dysregulation of the receptor tyrosine kinase AXL is known to promote cancer cell growth and survival in many sarcomas, including rare subtype, malignant peripheral nerve sheath tumors (MPNST). MPNSTs are largely chemoresistant carry a poor prognosis. an attractive potential therapeutic target, as it aberrantly expressed, its activation may be early event MPNST. However, effect inhibition on MPNST development progression not known. Here, we investigated role effects MEK1/2 co-inhibition...
Abstract Undifferentiated pleomorphic sarcoma (UPS) and malignant peripheral nerve sheath tumor (MPNST) are aggressive soft tissue sarcomas that do not respond well to current treatment modalities. The limited availability of UPS MPNST cell lines makes it challenging identify potential therapeutic targets in a laboratory setting. Understanding the urgent need for improved treatments these tumors cellular models led us generate additional study rare cancers further. Patient-derived were used...
Cells are equipped with multiple RNA regulatory mechanisms that control the expression of specific proteins. Here we report an miRNA expressed selectively in brain, miR‐128, regulates another RNA‐repressing mechanism: nonsense‐mediated decay (NMD). miR‐128 directly two NMD factors: helicase UPF1 and exon junction complex core component MLN51. Gain‐of‐function loss‐of‐function experiments demonstrated downregulates magnitude NMD, rescue provided evidence has this effect by acting through both...
Abstract Malignant peripheral nerve sheath tumors (MPNSTs) are a highly aggressive soft tissue sarcoma affecting approximately 10-15% of individuals with neurofibromatosis type 1 (NF1). MPNST development is characterized by an altered DNA methylation landscape and presents promising area for developing MPNST-specific biomarkers screening NF1 patients in the clinic. Here, using genome-wide profiling cohort 13 matched pairs MPNSTs adjacent neurofibroma tissues, along cell lines control...