A5068100015- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Cancer-related molecular mechanisms research
- T-cell and B-cell Immunology
- RNA modifications and cancer
- Renal Transplantation Outcomes and Treatments
- Genomics and Chromatin Dynamics
- Immunotherapy and Immune Responses
- Circular RNAs in diseases
- Immune Cell Function and Interaction
- RNA Research and Splicing
- Genomics and Phylogenetic Studies
- Bioinformatics and Genomic Networks
- Hematopoietic Stem Cell Transplantation
- Cytomegalovirus and herpesvirus research
- Reproductive tract infections research
- MicroRNA in disease regulation
- BRCA gene mutations in cancer
- Gut microbiota and health
- Microbial Community Ecology and Physiology
- Gene expression and cancer classification
- RNA and protein synthesis mechanisms
- Viral-associated cancers and disorders
- Catalytic Processes in Materials Science
- Urinary Tract Infections Management
Frederick National Laboratory for Cancer Research
2018-2025
National Cancer Institute
2018-2025
National Institutes of Health
2019-2025
Center for Cancer Research
2019-2025
Leidos (United States)
2018-2025
Leidos Biomedical Research Inc. (United States)
2018-2025
Virginia Commonwealth University
2011-2021
Children's Hospital of Richmond at VCU
2018
VCU Massey Comprehensive Cancer Center
2014-2017
Virginia Cancer Institute
2014-2017
Abstract The incidence of preterm birth exceeds 10% worldwide. There are significant disparities in the frequency among populations within countries, and women African ancestry disproportionately bear burden risk United States. In present study, we report a community resource that includes ‘omics’ data from approximately 12,000 samples as part integrative Human Microbiome Project. Longitudinal analyses 16S ribosomal RNA, metagenomic, metatranscriptomic cytokine profiles 45 90 term controls...
Noncoding RNAs have substantial effects in host–virus interactions. Circular (circRNAs) are novel single-stranded noncoding which can decoy other or RNA-binding proteins to inhibit their functions. The role of circRNAs is largely unknown the context Kaposi’s sarcoma herpesvirus (KSHV). We hypothesized that influence viral infection by inhibiting host and/or factors. Transcriptome analysis KSHV-infected primary endothelial cells and a B cell line identified human differentially regulated upon...
Recent advances in next-generation sequencing have revolutionized genomic research. 16S rRNA amplicon using paired-end on the MiSeq platform from Illumina, Inc., is being used to characterize composition and dynamics of extremely complex/diverse microbial communities. For this analysis Illumina platform, merging quality filtering reads are essential first steps data ensure accuracy reliability downstream analysis.We developed Merging Filtering Tool (MeFiT) combine these pre-processing into...
We report a novel mechanism of action ONC201 as mitochondria-targeting drug in cancer cells. was originally identified small molecule that induces transcription TNF-related apoptosis-inducing ligand (TRAIL) and subsequently kills cells by activating TRAIL death receptors. In this study, we examined toxicity on multiple human breast endometrial cell lines. attenuated viability all lines tested. Unexpectedly, not dependent either receptors nor caspases. Time-lapse live imaging revealed...
Non-coding RNAs (ncRNAs) play important roles in host-pathogen interactions; oncogenic viruses like Kaposi’s sarcoma herpesvirus (KSHV) employ ncRNAs to establish a latent reservoir and persist for the life of host. We previously reported that KSHV infection alters novel class RNA, circular (circRNAs). CircRNAs are alternative splicing isoforms regulate gene expression, but their importance is largely unknown. Here, we showed human circRNA, hsa_circ_0001400, induced by various pathogenic...
Nanoparticles have been an area of active research in recent years due to their properties, which can be greatly different from the bulk. In this work, we study sintering TiO2 nanoparticles using molecular dynamics simulations. Such occurs flame reactors where nanotitania is prepared via chloride process. Decrease free energy reduction surface main driving force for particles. Simulations, at various starting temperatures and orientations, indicate that process strongly affected by...
The size below which anatase nanoparticles become more stable than rutile (crossover diameter) is dependent on the environment of nanoparticles. It smaller for in vacuum those water and continues to decrease with increase temperature. Phase transformation between phases facilitated by enhanced ionic mobility at temperatures near melting point Multiparticle multiphase molecular dynamics simulations TiO2 undergoing sintering-induced phase transformations are reported here. Over time scales...
Vaginal lactobacilli can inhibit colonization by and growth of other bacteria, thereby preventing development bacterial vaginosis (BV). Amongst the lactobacilli, Lactobacillus crispatus appears to be particularly effective at inhibiting BV-associated bacteria. Nonetheless, some women who are colonized with this species still develop clinical BV. Therefore, we sought determine whether strains L. that colonize lactobacilli-dominated vaginal microbiomes distinct from The genomes isolates four (...
Abstract The centromeric histone H3 variant CENP-A is overexpressed in many cancers. mislocalization of to noncentromeric regions contributes chromosomal instability (CIN), a hallmark cancer. However, pathways that promote or prevent remain poorly defined. Here, we performed genome-wide RNAi screen for regulators localization which identified DNAJC9, J-domain protein implicated H3–H4 folding, as factor restricting mislocalization. Cells lacking DNAJC9 exhibit throughout the genome, and CIN...
This study uses molecular dynamics simulations performed in a parallel computing environment to investigate the adsorption of water molecules on surface anatase and rutile nanoparticles ranging from 2.5 4 nm at room temperature hydrothermal conditions. Phase enhancement occurs when these are immersed coverage per unit area increases with increase size. The residence time nanoparticle is ∼5−6 times longer than that under Examining oxygen hydrogen atom distribution surfaces, it found there two...
Brain-derived neurotrophic factor (BDNF) is a potent modulator of brain synaptic plasticity. Signaling defects caused by dysregulation its Ntrk2 (TrkB) kinase (TrkB.FL) and truncated receptors (TrkB.T1) have been linked to the pathophysiology several neurological neurodegenerative disorders. We found that upregulation Rbfox1, an RNA binding protein associated with intellectual disability, epilepsy autism, increases selectively hippocampal TrkB.T1 isoform expression. Physiologically,...
Abstract Cancer cells experience endoplasmic reticulum (ER) stress due to activated oncogenes and conditions of nutrient deprivation hypoxia. The ensuing unfolded protein response (UPR) is executed by ATF6, IRE1 PERK pathways. Adaptation mild ER promotes tumor cell survival aggressiveness. Unmitigated stress, however, will result in death a potential avenue for cancer therapies. Because this yin-yang nature it imperative that we fully understand the mechanisms dynamics UPR its contribution...
Abstract Background Kaposi sarcoma (KS) is a multicentric tumor caused by herpesvirus (KSHV) that leads to morbidity and mortality among people with HIV worldwide. KS commonly involves the skin but can occur in gastrointestinal tract (GI) severe cases. Methods RNA sequencing was used compare cellular KSHV gene expression signatures of GI lesions 44 paired samples from 19 participants alone or concurrent KSHV-associated diseases. Analyses identified transcriptionally active areas viral...
Abstract Herpesviruses require the host transcriptional machinery, inducing significant changes in gene expression to prioritize viral transcripts. We examined alpha- and gamma-herpesvirus alterations a type of alternative splicing, namely circular RNA (circRNA) synthesis. developed “Circrnas Host And viRuses anaLysis pIpEline” (CHARLIE) facilitate profiling. This method identified thousands back-splicing variants, including circRNA common lytic latent phases infection. Ours is first report...
Transfer RNA (tRNA) modifications are crucial for protein synthesis, but their position-specific physiological roles remain poorly understood. Here, we investigate the impact of N 4 -acetylcytidine (ac C), a highly conserved tRNA modification catalyzed by essential acetyltransferase Nat10. By targeting Thumpd1, nonessential adapter required Nat10-catalyzed acetylation, determine that loss acetylation leads to reduced levels Leu , increased ribosome stalling, and activation eIF2α...
Abstract Residual tumor cells can persist in a dormant state during clinical remissions that may last decades. The mechanisms lead to such growth control vs. eventual reactivation and macroscopic outgrowth remain unclear. Here, we report data from mouse model reveals key role of host immunity the cellular molecular dormancy. Abrogation myeloid-specific TGF-βRII expression (TβRII myeKO ) resulted an IFN-γ rich immune microenvironment. turn elevated KLF4-mediated SLURP1 production malignant...
Cancers often display immune escape, but the mechanisms are incompletely understood. Herein, we identify SMYD3 as a mediator of escape in human papilloma virus (HPV)-negative head and neck squamous cell carcinoma (HNSCC), an aggressive disease with poor response to immunotherapy pembrolizumab. depletion induces upregulation multiple type I interferon (IFN) antigen presentation machinery genes HNSCC cells. Mechanistically, binds regulates transcription UHRF1, encoding for reader H3K9me3,...
Abstract Low response rate, treatment relapse, and resistance remain key challenges for cancer with immune checkpoint blockade (ICB). Here we report that loss of specific tumor suppressors (TS) induces an inflammatory promotes suppressive microenvironment. Importantly, low expression these TSs is associated a higher inhibitory mediators. identify, by using in vivo CRISPR/Cas9 based loss-of-function screening, NF1, TSC1, TGF-β RII as regulating composition. Loss each three leads to...
Summary Whole exome sequencing ( WES ) was performed on stem cell transplant donor‐recipient D ‐ R pairs to determine the extent of potential antigenic variation at a molecular level. In small cohort pairs, high frequency sequence observed between donor and recipient exomes independent human leucocyte antigen HLA matching. Nonsynonymous, nonconservative single nucleotide polymorphisms were approximately twice as frequent in ‐matched unrelated, compared with related pairs. When mapped...
Multiple herpesviruses have been recently found to encode viral circular RNAs. Like cellular RNAs, these RNAs lack poly-A tails and their 5′ 3′ ends joined, which confers protection from RNA exonucleases. We examined the expression patterns of Kaposi’s sarcoma herpesvirus (KSHV) in various environments. performed deep sequencing circRNA-enriched total a KSHV-positive patient lymph node for comparison with previous circRNA-Seq results. that circvIRF4 is highly expressed sample relative both B...
Highlights•Exome sequencing may predict alloreactive donor T cell response using matrix mathematics.•HLA-matched transplant donor–recipient pairs exhibit different responses.AbstractImmune reconstitution kinetics and subsequent clinical outcomes in HLA-matched recipients of allogeneic stem transplantation (SCT) are variable difficult to predict. Considering SCT as a dynamical system allow sequence differences across the exomes donors be used simulate an response, which better outcome...