A5058056986- Epigenetics and DNA Methylation
- Pharmacogenetics and Drug Metabolism
- Gut microbiota and health
- Colorectal Cancer Screening and Detection
- Glycosylation and Glycoproteins Research
- Tryptophan and brain disorders
- Immune responses and vaccinations
- Drug Transport and Resistance Mechanisms
- Cancer-related Molecular Pathways
- PARP inhibition in cancer therapy
- Advanced biosensing and bioanalysis techniques
- Computational Drug Discovery Methods
- Inflammasome and immune disorders
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Protein Degradation and Inhibitors
- Immune Cell Function and Interaction
- Extracellular vesicles in disease
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- Bioinformatics and Genomic Networks
- Hippo pathway signaling and YAP/TAZ
Coriell Institute For Medical Research
2022-2025
Cancer Research Center
2025
Institute for Medical Research
2023-2025
The intestinal microbiota is an important environmental factor implicated in CRC development. Intriguingly, modulation of DNA methylation by gut has been reported preclinical models, although the relationship between tumor-infiltrating bacteria and CIMP status currently unexplored. In this study, we investigated tumor-associated 203 tumor cases validated findings using Cancer Genome Atlas datasets. We assessed abundance Bacteroides fragilis, Escherichia coli, Fusobacterium nucleatum,...
Abstract Background Epigenetic marks are encoded by DNA methylation and accumulate errors as organisms age. This drift correlates with lifespan, but the biology of how this occurs is still unexplained. We analyze age in mouse intestinal stem cells compare them to nonstem cells. Results Age-related changes identical cells, affect most prominently CpG islands correlate weakly gene expression. entropy, measured Jensen-Shannon Distribution, affects up 25% detectable sites a better measure aging...
Here we describe a new public pharmacogenetic (PGx) annotation database of large (n = 3,202) and diverse biospecimen collection 1000 Genomes Project cell lines DNAs. The is searchable with user friendly, web-based tool ( www.coriell.org/StarAllele/Search ). This resource leverages existing whole genome sequencing data PharmVar annotations to characterize *alleles for each in the collection. designed facilitate vitro functional characterization *allele haplotypes diplotypes as well support...
Abstract DNA methyltransferase and poly (ADP-ribose) polymerase inhibitors (DNMTis, PARPis) induce a stimulator of interferon genes (STING)-dependent pathogen mimicry response (PMR) in ovarian other cancers. Here, we showed that combining DNMTis PARPis upregulates expression the nucleic-acid sensor NFX1-type zinc finger-containing 1 protein (ZNFX1). ZNFX1 mediated induction PMR mitochondria, serving as gateway for STING-dependent interferon/inflammasome signaling. Loss cancer cells promoted...
Abstract Intestinal organoids, three-dimensional cultures from intestinal stem cells, are a potential model for studying aging. DNA methylation can serve as biological clock of aging, and we hypothesized that organoid could be valuable tool aging research. We compared in organoids to seen primary epithelium. Genome wide, found very substantial changes during establishment culture, with 27% total CpG sites undergoing loss (hypomethylation), 11% gaining (hypermethylation). The observed...
Abstract Epigenetic therapies that induce global DNA hypomethylation activate transcriptionally repressed transposable elements (TEs). The activation of a class TEs known as human endogenous retroviruses (HERVs) can trigger an innate antiviral response in cells called “viral mimicry”. Viral mimicry induced by aberrantly expressed HERVs stimulates interferon signaling genes resulting adaptive immune ultimately lead to immunogenic cell death. This heightened activity enhance the efficacy...
Gastroesophageal cancer (GEAC) remains a major health burden and urgently needs novel therapeutic targets. The inhibition of CDK9's activity holds the potential to be highly effective anti-cancer therapeutic. However, functional role CDK9, its targeting in GEAC, remain largely unknown. We aim evaluate degradation CDK9 GEAC treatment explore mechanisms. evaluated expression distribution tissue. designed synthesized degraders using proteolysis chimeras (PROTACs) strategy selected promising one...
<p>Supplementary Figures</p>
<div>Abstract<p>DNA methyltransferase (DNMT) and PARP inhibitors induce a stimulator of IFN gene–dependent pathogen mimicry response (PMR) in ovarian other cancers. In this study, we showed that combining DNMT upregulates expression the nucleic acid sensor NFX1-type zinc finger–containing 1 (ZNFX1) protein. ZNFX1 mediated induction PMR mitochondria, serving as gateway for IFN/inflammasome signaling. Loss cancer cells promoted proliferation spheroid formation <i>in...
Gastroesophageal cancer (GEAC) consists of upper GI malignancies the esophagus, gastroesophageal junction, or stomach. Despite recent advancements in treatment modalities, GEAC remains a major health burden and listed as second leading cause cancer-related deaths globally. poses significant challenge with short survival lack effective therapeutics. Thus, uncovering novel targets is urgent need. Cyclin-dependent kinase 9 (CDK9), one transcription-associated CDKs, has been implicated...
Aberrant transcription in cancer cells involves the silencing of tumor suppressor genes (TSGs) and activation oncogenes. Transcriptomic changes are associated with epigenomic alterations such as DNA-hypermethylation, histone deacetylation, chromatin condensation promoter regions silenced TSGs. To discover novel drugs that trigger TSG reactivation cells, we used a GFP-reporter system whose expression is by DNA hypermethylation deacetylation. After screening natural product drug library,...
Long-read sequencing technologies offer new opportunities to generate high-confidence phased whole-genome data for robust pharmacogenetic annotation. Here, we describe a user-friendly R package, ursaPGx, designed accept multi-sample VCF input files and output star allele annotations pharmacogenes annotated in PharmVar.
DNA methylation is an epigenetic process altered in cancer and ageing. Age-related drift can be used to estimate lifespan influenced by extrinsic factors such as diet. Here, we report that non-pathogenic microbiota accelerate age-related the colon when compared with germ-free mice. analyses showed IL10KO were associated changes 5% 4.1% of CpG sites, while mice both had 18% alterations. Microbiota, IL10KO, their combination 0.4%, 4% island methylation, respectively. These are comparable what...
Abstract Long-read sequencing technologies offer new opportunities to generate high confidence phased whole genome data for robust pharmacogenetic annotation. Here we describe a user-friendly R package, ursaPGx, designed accept multi-sample VCF input files and output star allele annotations pharmacogenes annotated in PharmVar.
Abstract DNA methyltransferase and poly(ADP-ribose) polymerase inhibitors (DNMTis, PARPis) induce a stimulator of interferon (IFN) genes (STING)-dependent pathogen mimicry response (PMR) in ovarian (OC) other cancers. We now show that combining DNMTis PARPis upregulates expression little-studied nucleic-acid sensor, NFX1-type zinc finger-containing 1 protein (ZNFX1). demonstrate ZNFX1 is novel master regulator for PMR induction mitochondria, serving as gateway STING-dependent PMR. In patient...
Abstract Here we describe a new public pharmacogenetic (PGx) annotation database of large (n=3202) and diverse biospecimen collection 1000 Genomes Project cell lines DNAs. The is searchable with user friendly, web-based tool ( www.coriell.org/StarAllele/Search ). This resource leverages existing whole genome sequencing data PharmVar annotations to characterize *alleles for each in the collection. designed facilitate vitro functional characterization *allele haplotypes diplotypes as well...