A5061589516- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- RNA modifications and cancer
- RNA Research and Splicing
- Cancer Genomics and Diagnostics
- Genomics and Rare Diseases
- Genomics and Chromatin Dynamics
- Bioinformatics and Genomic Networks
- RNA and protein synthesis mechanisms
- Genomic variations and chromosomal abnormalities
- SARS-CoV-2 and COVID-19 Research
- Metabolomics and Mass Spectrometry Studies
- Gene expression and cancer classification
- MicroRNA in disease regulation
- Epigenetics and DNA Methylation
- Gene Regulatory Network Analysis
- Liver Disease Diagnosis and Treatment
- Genetics and Neurodevelopmental Disorders
- Direction-of-Arrival Estimation Techniques
- Inflammation biomarkers and pathways
- Extracellular vesicles in disease
- Neurogenetic and Muscular Disorders Research
- Spaceflight effects on biology
- Blind Source Separation Techniques
- Corneal surgery and disorders
Children's Hospital of Philadelphia
2015-2023
University of Pennsylvania
2007-2022
National Human Genome Research Institute
2012-2016
National Institutes of Health
2012-2016
Institute of Molecular Biology and Biophysics
2013
Cardiff University
2013
Howard Hughes Medical Institute
2010-2012
Penn Center for AIDS Research
2007
The University of Texas at Dallas
2004-2006
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins bind to host mitochondrial proteins, likely inhibiting oxidative phosphorylation (OXPHOS) and stimulating glycolysis. We analyzed gene expression in nasopharyngeal autopsy tissues from patients with disease 2019 (COVID-19). In samples declining titers, the virus blocked transcription of a subset nuclear DNA (nDNA)–encoded OXPHOS genes, induced microRNA 2392, activated HIF-1α induce glycolysis, immune defenses...
Significance Spinal muscular atrophy (SMA), a common genetic motor neuron (MN) degenerative disease and leading hereditary cause of infant mortality, results from survival (SMN) protein deficiency. However, SMN’s ubiquitous expression housekeeping functions in biogenesis snRNPs, the spliceosome’s subunits, seems difficult to reconcile with SMA’s MN selective pathology. Here, we sequenced transcriptomes MNs adjacent white matter microdissected spinal cords presymptomatic SMA mice. This...
Accurate transcription is required for the faithful expression of genetic information. To understand molecular mechanisms that control fidelity transcription, we used novel sequencing technology to provide first comprehensive analysis in eukaryotic cells. Our results demonstrate errors can occur any gene, at location, and affect every aspect protein structure function. In addition, show multiple proteins safeguard evidence suggesting evade these layers RNA quality profoundly physiology...
Changes in the gut microbiota and mitochondrial genome are both linked with development of disease. To investigate why, we examined mice harboring various mutations genes that alter function. These studies revealed genetic variations altered composition community. In cross-fostering studies, found although initial community newborn was obtained from nursing mother, progressed toward characteristic microbiome unfostered pups same genotype within 2 months. Analysis DNA variants associated...
Diseases associated with mitochondrial DNA (mtDNA) mutations are highly variable in phenotype, large part because of differences the percentage normal and mutant mtDNAs (heteroplasmy) present within cell. For example, increasing heteroplasmy levels mtDNA tRNA Leu(UUR) nucleotide (nt) 3243A > G mutation result successively diabetes, neuromuscular degenerative disease, perinatal lethality. These phenotypes function nuclear (nDNA) gene expression, which recapitulated cybrid cell lines...
Mitochondrial DNA (mtDNA) variant pathogenicity interpretation has special considerations given unique features of the mtDNA genome, including maternal inheritance, heteroplasmy, threshold effect, absence splicing, and contextual effects haplogroups. Currently, there are insufficient standardized criteria for assessment, which leads to inconsistencies in clinical reporting. An international working group experts was assembled within Disease Sequence Data Resource Consortium obtained Expert...
Highlights•In silico predictions of miR-2392 as a miRNA involved with SARS-CoV-2•Overexpression produces similar biological response COVID-19 infection•miR-2392 is confirmed to circulate in serum and urine patients COVID-19•Development initiated potential antiviral therapeutic against COVID-19SummaryMicroRNAs (miRNAs) are small non-coding RNAs post-transcriptional gene regulation that have major impact on many diseases provide an exciting avenue toward therapeutics. From patient...
Massively parallel sequencing to identify rare variants is widely practiced in medical research and the clinic. Genome exome can genetic cause of a disease (primary results), but it also pathogenic underlying diseases that are not being sought (secondary or incidental results). A major controversy has developed surrounding return secondary results participants. We have piloted method analyze exomes participants at risk for cardiac arrhythmias, cardiomyopathies, sudden death.
<h3>Importance</h3> Autism spectrum disorders (ASD) are characterized by impairments in social interaction, communication, and repetitive or restrictive behavior. Although multiple physiologic biochemical studies have reported defects mitochondrial oxidative phosphorylation patients with ASD, the role of DNA (mtDNA) variation has remained relatively unexplored. <h3>Objective</h3> To assess what impact lineages encompassing ancient mtDNA functional polymorphisms, termed haplogroups, on ASD...
Defects in mitochondrial oxidative phosphorylation (OXPHOS) have been reported COVID-19 patients, but the timing and organs affected vary among reports. Here, we reveal dynamics of through transcription profiles nasopharyngeal autopsy samples from patients infected rodent models. While bioenergetics is repressed viral portal entry, it up regulated lung tissues deceased patients. In most disease stages organs, discrete OXPHOS functions are blocked by virus, this countered host broadly...
Abstract Background CTCF (CCCTC-binding factor) is an evolutionarily conserved zinc finger protein involved in diverse functions ranging from negative regulation of MYC, to chromatin insulation the beta-globin gene cluster, imprinting Igf2 locus. The 11 fingers are known differentially contribute CTCF-DNA interaction at different binding sites. It possible that differences conformation sites underlie CTCF's functional diversity. If so, may belong distinct classes, each compatible with a...
Reproducibility is receiving increased attention across many domains of science and genomics no exception. Efforts to identify copy number variations (CNVs) from exome sequence (ES) data have been increasing. Many algorithms published discover CNVs exomes a major challenge the reproducibility in other datasets. Here we test CNV calling under three conditions: generated by different sequencing centers; varying sample sizes; capture methodology.Four tools were tested: eXome Hidden Markov Model...
Summary Increasing evidence suggests that regulation of heterochromatin at the nuclear envelope underlies metabolic disease susceptibility and age‐dependent changes, but mechanism is unknown. Here, we profile lamina‐associated domains ( LAD s) using lamin B1 Ch IP ‐Seq in young old hepatocytes find that, although resides a large fraction both ages, third B1‐associated regions are bound exclusively each age vivo. Regions occupied by solely livers enriched for forkhead motif, Foxa pioneer...
Despite the presence of a cytosolic fatty acid synthesis pathway, mitochondria have retained their own means creating acids via mitochondrial (mtFASII) pathway. The reason for its conservation has not yet been elucidated. Therefore, to better understand role mtFASII in cell, we used thin layer chromatography characterize contribution pathway composition selected lipids. Next, performed metabolomic analysis on HeLa cells which was either hypofunctional (through knockdown acyl carrier protein,...
Purpose: To determine whether mitochondrial DNA haplogroups or rare variants associate with primary open-angle glaucoma in subjects of European descent. Methods: A case–control comparison age- and sex-matched cohorts 90 patients 95 population controls. Full sequences from peripheral blood were generated by next-generation sequencing compared to the revised Cambridge Reference Sequence define variants. Results: Most major H, J, K, U, T. Logistic regression analysis showed haplogroup U be...