A5054204936- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- Nuclear Receptors and Signaling
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Physiological and biochemical adaptations
- Marine Bivalve and Aquaculture Studies
- RNA regulation and disease
- Light effects on plants
- Marine Biology and Environmental Chemistry
- Hedgehog Signaling Pathway Studies
- Environmental Toxicology and Ecotoxicology
- interferon and immune responses
- Fibroblast Growth Factor Research
- Circadian rhythm and melatonin
- RNA Interference and Gene Delivery
- Effects and risks of endocrine disrupting chemicals
- Histone Deacetylase Inhibitors Research
University of Pennsylvania
2022-2024
Massachusetts Institute of Technology
2019-2023
Translational Therapeutics (United States)
2022-2023
University of Massachusetts Boston
2018-2021
Woods Hole Oceanographic Institution
2018-2019
Pre-mRNA splicing is surveilled at different stages by quality control (QC) mechanisms. The leukemia-associated DExH-box family helicase hDHX15/scPrp43 known to disassemble spliceosomes after splicing. Here, using rapid protein depletion and analysis of nascent mature RNA enrich for direct effects, we identify a widespread QC function DHX15 in human cells, consistent with recent vitro studies. We find that suboptimal introns weak splice sites, multiple branch points, cryptic are repressed...
Transcriptomics, high-throughput assays, and adverse outcome pathways (AOP) are promising approaches applied to toxicity monitoring in the 21st century, but development of these methods is challenging for nonmodel organisms emerging contaminants. For example, Endocrine Disrupting Compounds (EDCs) may cause reproductive impairments feminization male bivalves; however, mechanism linked this unknown. To develop mechanism-based biomarkers that be through an AOP, we exposed Mytilus edulis...
The severity of Alzheimer's disease (AD) progression involves a complex interplay genetics, age, and environmental factors orchestrated by histone acetyltransferase (HAT)-mediated neuroepigenetic mechanisms. While disruption Tip60 HAT action in neural gene control is implicated AD, alternative mechanisms underlying function remain unexplored. Here, we report novel RNA binding for addition to its function. We show that preferentially interacts with pre-mRNAs emanating from chromatin targets...
Chromatin regulation and alternative splicing are both critical mechanisms guiding gene expression. Studies have demonstrated that histone modifications can influence decisions, but less is known about how may impact chromatin. Here, we demonstrate several genes encoding histone-modifying enzymes alternatively spliced downstream of T cell signaling pathways, including HDAC7, a previously implicated in controlling expression differentiation cells. Using CRISPR-Cas9 editing cDNA expression,...
There is growing evidence that environmental toxicants can affect various physiological processes by altering DNA methylation patterns. However, very little known about the impact of toxicant-induced changes on gene expression The objective this study was to determine genome-wide in concomitant with altered patterns response 3, 3', 4, 4', 5-pentachlorobiphenyl (PCB126) exposure. We used PCB126 as a model chemical because mechanism action well-characterized, involving activation aryl...
Abstract Polychlorinated biphenyls (PCBs) are highly persistent and ubiquitously distributed environmental pollutants. Based on their chemical structure, PCBs classified into non-ortho-substituted ortho-substituted congeners. Non-ortho-substituted structurally similar to dioxin toxic effects mode of action well-established. In contrast, very little is known about the PCBs, particularly, during early development. The objective this study investigate exposure an environmentally prominent PCB...
Cocaine epigenetically regulates gene expression via changes in histone post-translational modifications (HPTMs). We previously found that the immediate early Nr4a1 is activated by cocaine mouse brain reward regions. However, few studies have examined multiple HPTMs at a single gene. Bivalent promoters are simultaneously enriched both activating (H3K4me3 (K4)) and repressive (H3K27me3 (K27)) HPTMs. As such, bivalent genes lowly expressed but poised for activity-dependent regulation. In this...
Summary The processing of transcripts from mammalian genes often occurs near in time and space to their transcription. Here we describe a phenomenon call exon-mediated activation transcription starts (EMATS) that affects thousands which the splicing internal exons impacts spectrum promoters used expression level host gene. We observed evolutionary gain new is associated with TSSs nearby increased gene expression. Inhibiting exon reduced promoters. Conversely, creation splice sites enable...
ABSTRACT Pre-mRNA splicing is surveilled at different stages by quality control (QC) mechanisms. The leukemia-associated DExH-box family helicase h DHX15/ sc Prp43, known to disassemble spliceosomes after splicing. Here, using rapid protein depletion and analysis of nascent mature RNA enrich for direct effects, we identified a widespread QC function DHX15 in human cells, consistent with recent vitro studies. We found that suboptimal introns weak splice sites, multiple branch points, cryptic...
ABSTRACT BACKGROUND Cocaine epigenetically regulates gene expression via changes in histone post-translational modifications (HPTMs). We previously found that the immediate early Nr4a1 is activated by cocaine mouse brain reward regions. HPTMs act combinatorically, yet few studies examine multiple at a single gene. Bivalent promoters are simultaneously enriched both activating (H3K4me3 (K4)) and repressive (H3K27me3 (K27)) HPTMs. As such, bivalent genes lowly expressed but poised for...