A5084646360- Genomics and Rare Diseases
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Genomics and Phylogenetic Studies
- RNA Research and Splicing
- Renal and related cancers
- Sarcoma Diagnosis and Treatment
- Neuroblastoma Research and Treatments
- Renal Diseases and Glomerulopathies
- Soft tissue tumor case studies
- Glioma Diagnosis and Treatment
- RNA and protein synthesis mechanisms
- Herpesvirus Infections and Treatments
- Immune Response and Inflammation
- Immune Cell Function and Interaction
- Chromosomal and Genetic Variations
- Genomic variations and chromosomal abnormalities
- Bacterial biofilms and quorum sensing
- Cytomegalovirus and herpesvirus research
- Chromatin Remodeling and Cancer
- Salmonella and Campylobacter epidemiology
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Bacterial Genetics and Biotechnology
- Childhood Cancer Survivors' Quality of Life
Nationwide Children's Hospital
2015-2024
The Ohio State University Wexner Medical Center
2020
The Ohio State University
2017-2020
Rasmussen College
2020
University of Massachusetts Chan Medical School
2010
UMass Memorial Medical Center
2010
Hitachi (United States)
2009
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...
Abstract Mesenchymal stem/stromal cells (MSCs) are widely studied by both academia and industry for a broad array of clinical indications. The collective body data provides compelling evidence the safety MSC therapy. However, generally accepted proof therapeutic efficacy has not yet been reported. In an effort to generate more effective cell product, investigators focused on modifying processing protocols enhance intrinsic biologic activity. Here, we report Good Manufacturing...
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...
Phosphatase and tensin homologue (PTEN) regulates cell growth survival through inhibition of the mammalian target rapamycin (MTOR) signalling pathway. Germline genetic variation PTEN is associated with autism, macrocephaly hamartoma tumour syndromes. The effect developmental somatic mutations on nervous system phenotypes not well understood, although brain mosaicism MTOR pathway genes an emerging cause cortical dysplasia epilepsy in paediatric population. Here we report two variants...
Abstract Variants in the AUTS2 gene are associated with a broad spectrum of neurological conditions characterized by intellectual disability, microcephaly, and congenital brain malformations. Here, we use human cerebral organoid model to investigate pathophysiology heterozygous de novo missense variant identified patient multiple impairments including primary microcephaly profound disability. Proband organoids exhibit reduced growth, deficits neural progenitor cell (NPC) proliferation...
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...
Many genetic studies of intractable epilepsy in pediatric patients primarily focus on inherited, constitutional deficiencies identified patient blood. Recently, have revealed somatic mosaicism associated with which variants are present only a subset brain cells. We hypothesize that tissue-specific, represents an important etiology and aim to discover alterations epilepsy-affected tissue.We pursued research study identify mosaicism, using next-generation sequencing (NGS) technologies,...
Abstract Nontypeable Haemophilus influenzae (NTHI) is a human-restricted pathogen with an essential requirement for heme–iron acquisition. We previously demonstrated that microevolution of NTHI promotes stationary phase survival in response to transient restriction. In this study, we examine the metabolic contributions biofilm formation using evolved strain, RM33. Quantitative analyses identified 29 proteins, 55 transcripts, and 31 metabolites significantly changed within vitro biofilms...
Typhoid fever is caused primarily by Salmonella enterica serovar Typhi. Approximately 3% to 5% of individuals infected with S Typhi become chronic carriers the gallbladder (GB) as site persistence, gallstones within GB are a platform on which bacteria form biofilm. human-restricted pathogen; therefore, asymptomatic represent critical reservoir for further spread disease. To examine dynamics biofilm during carriage, human gallstone (GS) environment was simulated growing biofilms...
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....
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...
L-arabinose inducible promoters are commonly used in gene expression analysis. However, nutrient source and availability also play a role biofilm formation; therefore, metabolism could impact development. In this study we examined the of on Salmonella enterica serovar Typhimurium (S. Typhimurium) formation. Using mutants impaired for transport L-arabinose, showed that negatively impacts S. formation vitro. When is abrogated, returned to baseline levels. without ability import extracellular...
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates cellular processes in cancer and immunity, including innate immune cell development effector function. However, the transcriptional repertoire through which AHR mediates these effects remains largely unexplored. To elucidate elements directly regulated by natural killer (NK) cells, we performed RNA chromatin immunoprecipitation sequencing on NK cells exposed to agonist or antagonist. We show mature...
Abstract The renal collecting duct consists of intercalated cells (ICs) and principal (PCs). We have previously demonstrated that ducts a role in the innate immune defense kidney. Transcriptomics is an important tool used to enhance systems-level understanding cell biology. However, transcriptomics performed on whole kidneys provides limited insight gene expression, because these comprise small fraction total kidney cells. Recently we generated reporter mouse models enrich specific PC ICs...
Abstract Oncogenesis in PLAG1‐ rearranged tumors often results from PLAG1 transcription factor overexpression driven by promoter‐swapping between constitutively expressed fusion partners. ‐rearranged demonstrate diverse morphologies. This study adds to this morphologic heterogeneity introducing two with rearrangements that display distinct histologic features. The first arose the inguinal region of a 3‐year‐old, appeared well‐circumscribed multinodular pattern, and harbored fusions:...
Typhoid fever, caused primarily by Salmonella enterica serovar Typhi (S Typhi), is a life-threatening systemic disease responsible for significant morbidity and mortality worldwide. Three to 5% of individuals infected with S become chronic carriers due bacterial persistence in the gallbladder. We have demonstrated that forms biofilms on gallstones establish gallbladder carriage. However, an in-depth molecular understanding carriage gallbladder, from perspective both pathogen host, poorly...
Next-generation sequencing (NGS) assays can sensitively detect somatic variation, and increasingly enable the identification of complex structural rearrangements. A subset infantile spindle cell sarcomas, particularly congenital mesoblastic nephromas with classic or mixed histology, have rearrangement in form internal tandem duplications (ITD) involving EGFR. We performed prospective analysis to identify EGFR ITD through clinical research studies, as well retrospective quantify frequency...
Abstract Primary spinal cord tumors contribute to ≤ 10% of central nervous system in individuals pediatric or adolescent age. Among intramedullary tumors, ependymomas make up ~ 30% this rare tumor population. A twelve-year-old male presented with an intradural, extramedullary mass occupying the dorsal canal from C6 through T2. Gross total resection and histopathology revealed a World Health Organization (WHO) grade 2 ependymoma. He recurred eleven months later extension C2 T1-T2. Subtotal...
Background Severe innate immune suppression, termed immunoparalysis, is associated with increased risks of nosocomial infection and mortality in children septic shock. Currently, immunoparalysis cannot be clinically diagnosed children, mechanisms remain unclear. Transcriptomic studies identify subsets downregulation genes within adaptive pathways, but assays function have not been performed as part these studies, little known about transcriptomic profiles immunoparalysis. Methods We a nested...