A5065907373- Mitochondrial Function and Pathology
- Cell death mechanisms and regulation
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- RNA modifications and cancer
- Glioma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Extracellular vesicles in disease
- Cancer, Hypoxia, and Metabolism
- Inflammation biomarkers and pathways
- PARP inhibition in cancer therapy
- Molecular Biology Techniques and Applications
- MicroRNA in disease regulation
- Microtubule and mitosis dynamics
- Autophagy in Disease and Therapy
- FOXO transcription factor regulation
- ATP Synthase and ATPases Research
- Ion-surface interactions and analysis
- Circular RNAs in diseases
- Pancreatitis Pathology and Treatment
- Apelin-related biomedical research
- RNA Interference and Gene Delivery
- Nanopore and Nanochannel Transport Studies
- SARS-CoV-2 detection and testing
- DNA Repair Mechanisms
Centre for Genomic Regulation
2022-2025
Institute of Bioorganic Chemistry
2015-2024
Neurological Surgery
2012-2023
The Ohio State University
2012-2023
Mayo Clinic in Arizona
2023
First Affiliated Hospital of Xi'an Jiaotong University
2023
The Ohio State University Wexner Medical Center
2023
University of Alabama at Birmingham
2016-2018
Institute of Bioorganic Chemistry
2018
Mayo Clinic
2012
Unresectable glioblastoma (GBM) cells in the invading tumor edge can act as seeds for recurrence. The molecular and phenotypic properties of these remain elusive. Here, we report that core have two distinct types glioma stem-like (GSCs) resemble proneural (PN) mesenchymal (MES) subtypes, respectively. Upon exposure to ionizing radiation (IR), GSCs, initially enriched a CD133+ PN signature, transition CD109+ MES subtype C/EBP-β-dependent manner. Our gene expression analysis paired cohorts...
Glioma stem-like cells (GSC) with tumor-initiating activity orchestrate the cellular hierarchy in glioblastoma and engender therapeutic resistance. Recent work has divided GSC into two subtypes a mesenchymal (MES) population as more malignant subtype. In this study, we identify FOXD1-ALDH1A3 signaling axis determinant of MES phenotype. The transcription factor FOXD1 is expressed predominantly patient-derived cultures enriched MES, but not proneural shRNA-mediated attenuation ablates their...
Abstract Intratumor spatial heterogeneity facilitates therapeutic resistance in glioblastoma (GBM). Nonetheless, understanding of GBM is largely limited to the surgically resectable tumor core lesion while seeds for recurrence reside unresectable edge. In this study, stratification and edge demonstrates clinically relevant surgical sequelae. We establish regionally derived models that retain their identity a cell autonomous manner. Upon xenotransplantation, edge-derived cells show higher...
Ovarian cancer ascites is a native medium for cells that allows investigation of their secretome in natural environment. This interest as promising source potential biomarkers, and also cell–cell communication. The aim this study was to elucidate specific features the malignant metabolome proteome. In order omit components systemic response formation, we compared with cirrhosis ascites. Metabolome analysis revealed 41 differed significantly between Most identified cancer-specific metabolites...
Abstract Purpose: Glioblastoma multiforme (GBM) is a devastating disease. Recent studies suggest that the stem cell properties of GBM contribute to development therapy resistance. Experimental Design: The expression Survivin and Ran was evaluated by immunohistochemistry with tissues, quantitative reverse transcriptase (qRT)-PCR immunocytochemistry patient-derived sphere cultures. With computational structure-based drug design, 11 small-molecule compounds were designed, synthesized, as...
Accumulating evidence suggests that glioma stem cells (GSCs) are important therapeutic targets in glioblastoma (GBM). In this study, we identified NIMA-related kinase 2 (NEK2) as a functional binding protein of enhancer zeste homolog (EZH2) plays critical role the posttranslational regulation EZH2 GSCs. NEK2 was among most differentially expressed kinase-encoding genes GSC-containing cultures (glioma spheres), and it required for vitro clonogenicity, vivo tumor propagation, radioresistance....
Glioblastoma (GBM) is one of the most aggressive human cancers with a median survival less than two years. A distinguishing pathological feature GBM high degree inter- and intratumoral heterogeneity. Intertumoral heterogeneity has been extensively investigated on genomic, methylomic, transcriptomic, proteomic metabolomics levels, however only few studies describe because lack methods allowing to analyze samples spatial resolution. Here, we applied TOF-SIMS (Time-of-flight secondary ion mass...
Abstract Extensive neovascularization is a hallmark of glioblastoma (GBM). In addition to supplying oxygen and nutrients, vascular endothelial cells provide trophic support GBM via paracrine signaling. Here we report that Endocan ( ESM1 ), an endothelial-secreted proteoglycan, confers enhanced proliferative, migratory, angiogenic properties regulates their spatial identity. Mechanistically, exerts at least part its functions direct binding activation the PDGFRA receptor. Subsequent...
In the eukaryotic cell, spliceosomes assemble onto pre-mRNA cotranscriptionally. Spliceosome assembly takes place in context of chromatin environment, suggesting that state may affect splicing. The molecular details and mechanisms through which affects splicing, however, are still unclear. Here, we show a role for histone methyltransferase Set2 its modification, H3K36 methylation, splicing high-throughput sequencing. Moreover, effect methylation on is mediated chromodomain protein Eaf3. We...
Short nuclear regulatory RNAs play a key role in the main stages of maturation precursors major RNA species. Small (snRNAs) form core spliceosome and are responsible for splicing pre-mRNA molecules. nucleolar (snoRNAs) direct post-transcriptional modification pre-rRNAs. A promising strategy development non-coding (ncRNAs) mimicking molecules is introduction modified nucleotides, which normally present natural ncRNAs, into structure synthetic RNAs. We have created set snoRNAs snRNA analogs...
Abnormal pre-mRNA splicing regulation is common in cancer, but the effects of chemotherapy on this process remain unclear. To evaluate effect slicing regulation, we performed meta-analyses previously published transcriptomic, proteomic, phosphoproteomic, and secretome datasets. Our findings were verified by LC-MS/MS, western blotting, immunofluorescence, FACS analyses multiple cancer cell lines treated with cisplatin pladienolide B. results revealed that different types lead to similar...
Gliomas are fast growing and highly invasive brain tumors, characterized by tumor microenvironment acidification that drives glioma cell growth migration. Channels containing Acid-sensing Ion Channel 1a subunit (ASIC1a) mediate amiloride-sensitive cation influx in late stage cells, but not normal astrocytes. Thus, selective targeting of ASIC1a can be a perspective strategy for treatment. Here, expression U251 MG A172 astrocytes, was demonstrated. Recombinant analog mambalgin-2 from black...
PON2 belongs to the paraoxonase protein family that consists of lactone hydrolyzing enzymes with different substrate specificities. Unlike other members family, exhibits substantial antioxidant activity, is localized predominantly inside cell, and ubiquitously expressed in all human tissues. Previously, it was proffered defense against pathogens, such as Pseudomonas aeruginosa, main function paraoxonases. However, recent findings have highlighted important role played by protection oxidative...
Abstract Ovarian cancer often develops resistance to conventional therapies, hampering their effectiveness. Here, using ex vivo paired ovarian ascites obtained before and after chemotherapy in vitro therapy-induced secretomes, we show that molecules secreted by cells upon therapy promote cisplatin enhance DNA damage repair recipient cells. Even a short-term incubation of chemonaive with secretomes induces changes resembling those are observed chemoresistant patient-derived tumor long-term...