A5039872505- PARP inhibition in cancer therapy
- Cancer, Lipids, and Metabolism
- Cancer, Hypoxia, and Metabolism
- Chromatin Remodeling and Cancer
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Signaling Pathways in Disease
- interferon and immune responses
- Endoplasmic Reticulum Stress and Disease
- Immunotherapy and Immune Responses
- Adipose Tissue and Metabolism
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Peptidase Inhibition and Analysis
- Cancer Mechanisms and Therapy
- Protein Degradation and Inhibitors
- Peroxisome Proliferator-Activated Receptors
- Immune cells in cancer
- Lipid metabolism and biosynthesis
- RNA Research and Splicing
- Cancer-related gene regulation
- Cancer-related molecular mechanisms research
- Genomics and Chromatin Dynamics
- Ubiquitin and proteasome pathways
- Cytomegalovirus and herpesvirus research
University of Tsukuba
2016-2025
The Wistar Institute
2019-2023
University of California, Irvine
2019
Abstract Cyclic cGMP-AMP synthase (cGAS) is a pattern recognition cytosolic DNA sensor that essential for cellular senescence. cGAS promotes inflammatory senescence-associated secretory phenotype (SASP) through recognizing cytoplasmic chromatin during cGAS-mediated inflammation the antitumor effects of immune checkpoint blockade. However, mechanism by which recognizes unknown. Here we show topoisomerase 1-DNA covalent cleavage complex (TOP1cc) both necessary and sufficient SASP TOP1cc...
Abstract The tumor immune microenvironment is influenced by the epigenetic landscape of tumor. Here, we have identified SETDB1–TRIM28 complex as a critical suppressor antitumor immunity. An CRISPR–Cas9 screen 1,218 chromatin regulators TRIM28 PD-L1 expression. We then revealed that expression negatively correlated with infiltration effector CD8+ T cells. Inhibition simultaneously upregulated and activated cyclic GMP–AMP synthase (cGAS)–stimulator interferon genes (STING) innate response...
Abstract ARID1A inactivation causes mitotic defects. Paradoxically, cancers with high mutation rates typically lack copy number alterations (CNAs). Here, we show that defects in telomere cohesion, which selectively eliminates gross chromosome aberrations during mitosis. promotes the expression of cohesin subunit STAG1 is specifically required for cohesion. damage can be rescued by expression. Colony formation capability single cells G 2 /M, but not 1 phase, significantly reduced...
Abstract Chemoresistance is one of the leading causes mortality in breast cancer (BC). Understanding molecules regulating chemoresistance critical order to combat chemoresistant BC. Drug efflux pump ABCB1 overexpressed neoplasms where it effluxes various chemotherapeutic agents from cells. Because expressed normal and cancerous cells alike, attempts at targeting directly have failed due low specificity disruption tissue. A proposed method inhibit target its cancer-specific, upstream...
Abstract CARM1 is often overexpressed in human cancers including ovarian cancer. However, therapeutic approaches based on expression remain to be an unmet need. Cancer cells exploit adaptive responses such as the endoplasmic reticulum (ER) stress response for their survival through activating pathways IRE1α/XBP1s pathway. Here, we report that CARM1-expressing cancer are selectively sensitive inhibition of regulates XBP1s target gene and directly interacts with during ER response. Inhibition...
Linker histones constitute a class of proteins that are responsible for the formation higher-order chromatin structures. Core integral components nucleosome core particles (NCPs), whereas linker bind to DNA between NCPs. Heterochromatin protein 1 binding 3 (HP1BP3) displays sequence similarity histones, with exception presence three globular domains in its central region. However, function HP1BP3 as histone has not been analyzed previously. The present study aimed elucidate full-length...
NPM1/nucleophosmin is frequently overexpressed in various tumors, although the oncogenic role of NPM1 remains unclear. Here we revealed link between and nuclear factor-κB (NF-κB), a master regulator inflammation. We found that knockdown decreased NF-κB-mediated transcription selected target genes by decreasing recruitment NF-κB p65 to gene promoters. directly associated with DNA binding domain enhance its activity without being part DNA-NF-κB complex. This result suggests requires...
The SWI/SNF chromatin-remodeling complex is frequently altered in human cancers. For example, the component
The arginine methyltransferase CARM1 exhibits high expression levels in several human cancers, with the trend also observed ovarian cancer. However, therapeutic approaches targeting tumors that overexpress have not been explored. Cancer cells exploit metabolic reprogramming such as fatty acids for their survival. Here we report promotes monounsaturated acid synthesis and represents a vulnerability CARM1-expressing of genes encoding rate-limiting enzymes
The extent to which effector CD8+ T cells infiltrate into tumors is one of the major predictors clinical outcome for patients with epithelial ovarian cancer (EOC). Immune cell infiltration EOC a complex process that could be affected by epigenetic makeup tumor. Here, we have demonstrated lysine 4 histone H3 (H3K4) demethylase, (lysine-specific demethylase 5A; KDM5A) impairs immune and inhibits antitumor responses. Mechanistically, found KDM5A silenced genes involved in antigen processing...
Abstract NIPBL is an essential loader of cohesin to mediate sister chromatid cohesion and chromatin loop organization. mutations cause Cornelia de Lange Syndrome. How NIPBL’s genomic localization specified not fully understood. We found that localizes the nucleolus in RNA-dependent manner binds directly ribosomal RNA (rRNA). identified two binding domains vitro, both which are required for efficient rRNA vivo. DNA (rDNA) RNA-stimulated manner, recruits PAF1 promotes pre-rRNA transcription....
<div>Abstract<p>The SWI/SNF chromatin-remodeling complex is frequently altered in human cancers. For example, the component <i>ARID1A</i> mutated more than 50% of ovarian clear cell carcinomas (OCCC), for which effective treatments are lacking. Here, we report that ARID1A transcriptionally represses IRE1α–XBP1 axis endoplasmic reticulum (ER) stress response, confers sensitivity to inhibition pathway <i>ARID1A</i>-mutant OCCC. mutational status correlated...
<p>Figure S5 shows that B-I09 is not effective against ARID1A wildtype OCCCs.</p>
<p>Figure S1 shows that ARID1A regulates the IRE1a/XBP1 pathway.</p>
<p>Figure S2 shows that XBP1 and ERN1 are direct ARID1A target genes.</p>