A5031984861- Classical Antiquity Studies
- Cancer Genomics and Diagnostics
- Genomics and Rare Diseases
- RNA modifications and cancer
- Genomics and Phylogenetic Studies
- Archaeology and Historical Studies
- Glioma Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- Classical Studies and Legal History
- Metabolomics and Mass Spectrometry Studies
- Genetics and Neurodevelopmental Disorders
- Law, logistics, and international trade
- RNA Research and Splicing
- American Constitutional Law and Politics
- Genomic variations and chromosomal abnormalities
- Acute Lymphoblastic Leukemia research
- RNA and protein synthesis mechanisms
- Neuroblastoma Research and Treatments
- Congenital heart defects research
- Ancient Egypt and Archaeology
- Spectroscopy and Chemometric Analyses
- Chromatin Remodeling and Cancer
- Chromosomal and Genetic Variations
- Bacterial Genetics and Biotechnology
- Childhood Cancer Survivors' Quality of Life
Nationwide Children's Hospital
2014-2024
Thermo Fisher Scientific (United States)
2023
St. Jude Children's Research Hospital
2023
York University
2010-2022
Rasmussen College
2020-2021
Michigan Medicine
2020
The Ohio State University
2012-2017
Wright State University
2007-2009
University of Delaware
2008
Mississippi State University
2008
Abstract The AURORA US Metastasis Project was established with the goal to identify molecular features associated metastasis. We assayed 55 females metastatic breast cancer (51 primary cancers and 102 metastases) by RNA sequencing, tumor/germline DNA exome low-pass whole-genome sequencing global methylation microarrays. Expression subtype changes were observed in ~30% of samples coincident clonality shifts, especially involving HER2. Downregulation estrogen receptor (ER)-mediated cell–cell...
The transcription factor AmrZ regulates genes important for P. aeruginosa virulence, including type IV pili, extracellular polysaccharides, and the flagellum; however, global effect of on gene expression remains unknown, therefore, may directly regulate many additional that are crucial infection. Compared to wild strain, a ΔamrZ mutant exhibits rugose colony phenotype, which is commonly observed in variants accumulate intracellular second messenger cyclic diguanylate (c-di-GMP). Cyclic...
While advances in genome sequencing technology make population-scale genomics a possibility, current approaches for analysis of these data rely upon parallelization strategies that have limited scalability, complex implementation and lack reproducibility. Churchill, balanced regional strategy, overcomes challenges, fully automating the multiple steps required to go from raw reads variant discovery. Through novel deterministic techniques, Churchill allows computationally efficient high-depth...
Abstract Objective Epilepsy‐associated developmental lesions, including malformations of cortical development and low‐grade tumors, represent a major cause drug‐resistant seizures requiring surgical intervention in children. Brain‐restricted somatic mosaicism has been implicated the genetic etiology these lesions; however, many contributory genes remain unidentified. Methods We enrolled 50 children who were undergoing epilepsy surgery into translational research study. Resected tissue was...
Recent characterizations of pioneer transcription factors provide insights into their structures and patterns chromatin recognition associated with roles in cell fate commitment transformation. Intersecting these basic science concepts, identification (PFs) fused together as driver translocations childhood cancers raises questions whether fusions retain the fundamental ability to invade repressed chromatin, consistent monomeric PF constituents. This study defines cellular localization...
Abstract Background Cancers exhibit complex transcriptomes with aberrant splicing that induces isoform-level differential expression compared to non-diseased tissues. Transcriptomic profiling using short-read sequencing has utility in providing a cost-effective approach for evaluating isoform expression, although assembly displays limitations the accurate inference of full-length transcripts. Long-read RNA (Iso-Seq), Pacific Biosciences (PacBio) platform, can overcome such by sequence...
Single exon duplications account for disease in a minority of Duchenne muscular dystrophy patients. Exon skipping these patients has the potential to be highly therapeutic through restoration full-length dystrophin expression. We conducted 48-week open label study casimersen and golodirsen 3 subjects with an 45 or 53 duplication. Two (aged 18 23 years) were non-ambulatory at baseline. Upper limb, pulmonary, cardiac function appeared stable 2 whom they could evaluated. Dystrophin expression...
Two sisters (ages 16 yr and 15 yr) have been followed by our clinical genetics team for several years. Both girls severe intellectual disability, hypotonia, seizures, distinctive craniofacial features. The parents are healthy no other children. Oligo array, fragile X testing, numerous single-gene tests were negative. All four family members underwent research exome sequencing, which revealed a heterozygous nonsense mutation in ASXL3 (p.R1036X) that segregated with disease. Exome data...
Survival of patients with acute myeloid leukemia (AML) is inversely associated age, but the impact race on outcomes adolescent and young adult (AYA; range, 18-39 years) unknown. We compared survival 89 non-Hispanic Black 566 White AYA AML treated frontline Cancer Leukemia Group B/Alliance for Clinical Trials in Oncology protocols. Samples 327 (50 277 White) were analyzed via targeted sequencing. Integrated genomic profiling was performed select longitudinal samples. had worse outcomes,...
Congenital heart disease (CHD) is a common group of birth defects with strong genetic contribution to their etiology, but historically the diagnostic yield from exome studies isolated CHD has been low. Pleiotropy, variable expressivity, and difficulty accurately phenotyping newborns contribute this problem. We hypothesized that performing sequencing on selected individuals in families multiple members affected by left-sided CHD, then filtering variants population frequency, silico predictive...
Pediatric cancers typically have a distinct genomic landscape when compared to adult and frequently carry somatic gene fusion events that alter expression drive tumorigenesis. Sensitive specific detection of fusions through the analysis next-generation-based RNA sequencing (RNA-Seq) data is computationally challenging may be confounded by low tumor cellularity or underlying complexity. Furthermore, numerous computational tools are available identify from supporting RNA-Seq reads, yet each...
Gastroblastomas are rare tumors with a biphasic epithelioid/spindle cell morphology that typically present in early adulthood and have recurrent MALAT1-GLI1 fusions. We describe an adolescent patient Wiskott-Aldrich syndrome who presented large submucosal gastric tumor morphology. Despite histologic features consistent gastroblastoma, fusion was not found this patient's tumor; instead, comprehensive molecular profiling identified novel EWSR1-CTBP1 no other significant genetic alterations....
Meningiomas are a central nervous system tumor primarily afflicting adults, with <1% of cases diagnosed during childhood or adolescence. Somatic variation in NF2 may be found ∼50% meningiomas, other genetic drivers (eg, SMO, AKT1, TRAF7) contributing to wild-type tumors. is an upstream negative regulator YAP signaling and loss the protein product, Merlin, results overexpression target gene transcription. This mechanism dysregulation described NF2-driven but further work necessary understand...
Exome sequencing (ES) has become an important tool in pediatric genomic medicine, improving identification of disease-associated variation due to assay breadth. Depth is also afforded by ES, enabling detection lower-frequency mosaic compared Sanger the studied tissue, thus enhancing diagnostic yield. Within a tertiary-care hospital, we report two years clinical ES data from probands evaluated for genetic disease assess yield, characteristics causal variants, and prevalence mosaicism among...
Abstract Background The role of synonymous single-nucleotide variants in human health and disease is poorly understood, yet evidence suggests that this class “silent” genetic variation plays multiple regulatory roles both transcription translation. One mechanism by which codons direct modulate the translational process through alteration elaborate structure formed single-stranded mRNA molecules. While tools to computationally predict effect non-synonymous on protein are plentiful, analogous...