A5046136462- Molecular Biology Techniques and Applications
- PI3K/AKT/mTOR signaling in cancer
- DNA Repair Mechanisms
- RNA Research and Splicing
- PARP inhibition in cancer therapy
- Glioma Diagnosis and Treatment
- CRISPR and Genetic Engineering
- Renal and related cancers
- Cancer Genomics and Diagnostics
- Protein Tyrosine Phosphatases
- Mitochondrial Function and Pathology
- FOXO transcription factor regulation
- Plant Disease Resistance and Genetics
- RNA regulation and disease
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- interferon and immune responses
- Plant Virus Research Studies
- Biomedical Research and Pathophysiology
- Cell Adhesion Molecules Research
- Carcinogens and Genotoxicity Assessment
- Advanced Fluorescence Microscopy Techniques
- Cancer-related Molecular Pathways
- Genetic factors in colorectal cancer
- Infectious Diseases and Mycology
Yale University
2016-2023
Howard Hughes Medical Institute
2021
Dana-Farber Cancer Institute
2021
Harvard University
2021
2-Hydroxyglutarate (2HG) exists as two enantiomers, (R)-2HG and (S)-2HG, both are implicated in tumor progression via their inhibitory effects on α-ketoglutarate (αKG)-dependent dioxygenases. The former is an oncometabolite that induced by the neomorphic activity conferred isocitrate dehydrogenase 1 (IDH1) IDH2 mutations, whereas latter produced under pathologic processes such hypoxia. We report IDH1/2 mutations induce a homologous recombination (HR) defect renders cells exquisitely...
Abstract The blood disorder, β-thalassaemia, is considered an attractive target for gene correction. Site-specific triplex formation has been shown to induce DNA repair and thereby catalyse genome editing. Here we report that triplex-forming peptide nucleic acids (PNAs) substituted at the γ position plus stimulation of stem cell factor (SCF)/c-Kit pathway yielded high levels editing in haematopoietic cells (HSCs) a mouse model human β-thalassaemia. Injection thalassemic mice with SCF...
Background In patients with autosomal dominant polycystic kidney disease (ADPKD), most of whom have a mutation in PKD1 or PKD2 , abnormally large numbers macrophages accumulate around cysts and promote their growth. Research by us others has suggested that monocyte chemoattractant protein-1 (Mcp1) may be signal for macrophage-mediated cyst Methods To define the role Mcp1 promoting growth, we used mice inducible knockout Pkd1 alone (single knockout) both (double murine renal tubule. Levels...
Dysregulation of long interspersed nuclear element 1 (LINE-1, L1), a dominant class transposable elements in the human genome, has been linked to neurodegenerative diseases, but whether elevated L1 expression is sufficient cause neurodegeneration not directly tested. Here, we show that cerebellar significantly ataxia telangiectasia patients and strongly anti-correlated with epigenetic silencers. To examine role disease etiology, developed an approach for direct targeting promoter...
The heavy metal nickel is a known carcinogen, and occupational exposure to compounds has been implicated in human lung nasal cancers. Unlike many other environmental carcinogens, however, does not directly induce DNA mutagenesis, the mechanism of nickel-related carcinogenesis remains incompletely understood. Cellular leads signaling pathway activation, transcriptional changes epigenetic remodeling, processes also impacted by hypoxia, which itself promotes tumor growth without causing direct...
Abstract miR-155 is an oncogenic miRNA that often overexpressed in cancer and associated with poor prognosis. can target several DNA repair factors, including RAD51, MLH1, MSH6, its overexpression results increased mutation frequency vitro, although the mechanism has yet to be fully understood. Here, we demonstrate of drives both vitro vivo, promoting genomic instability by affecting multiple pathways. causes a decrease homologous recombination, but yields concurrent increase error-prone...
// Susan E. Scanlon 1, 2 , Denise C. Hegan 3 Parker L. Sulkowski and Peter M. Glazer 1 Department of Therapeutic Radiology, Yale University School Medicine, New Haven, CT, USA Experimental Pathology, Genetics, Correspondence to: Glazer, email: peter.glazer@yale.edu Keywords: DNA repair; homologous recombination; von Hippel-Lindau (VHL); hypoxia; PARP inhibitor Received: October 30, 2017 Accepted: November 28, Published: December 19, ABSTRACT The ( VHL ) tumor suppressor gene is inactivated...
Abstract DNA double-strand breaks (DSB) are the most cytotoxic lesions, and up to 90% of DSBs require repair by nonhomologous end joining (NHEJ). Functional genomic analyses patient-derived melanomas revealed that PTEN loss is associated with NHEJ deficiency. In PTEN-null melanomas, complementation rescued defect; conversely, suppression compromised NHEJ. Mechanistic studies promotes through direct induction expression XRCC4-like factor (NHEJ1/XLF), which functions in bridging ligation. was...
The authors have withdrawn their manuscript because many of the experiments described in this paper not been reproducible, or at least are robust, hands other members Kaelin Laboratory who were initially involved work. While we do see apparent secretion histone H3 under some conditions, it is usually accompanied by H4. In regard, Halo tagged-histone and Halo-tagged H4 constructs used for single molecule imaging studies reported, which seemingly confirmed specific transfer H3, purported to be...
Abstract Environmental exposure to certain heavy metals, such as nickel and arsenic, has been implicated in a variety of human cancers, including lung, skin, digestive track, bladder cancers. Importantly, the mechanism underlying carcinogenicity arsenic remains poorly understood they do not induce direct DNA mutagenesis. However, lead global changes chromatin structure transcription, many similar effects hypoxia. Since hypoxia is known regulate different repair pathways, we investigated...
ABSTRACT Previous studies have revealed that dysregulation of long interspersed nuclear element 1 (LINE-1), a dominant class transposable elements in the human genome, correlates with neurodegeneration 1–3 . Yet whether LINE-1 is causal to disease pathogenesis has not been proven directly. Here, we demonstrate expression evolutionarily younger families elevated cerebella ataxia telangiectasia (AT) patients, which was correlated extensive downregulation epigenetic silencers. To examine...
<p>Additional Characterization of PTEN K128R</p>
<p>Additional DNA Repair Data with PTEN-Complemented Cells</p>
<p>Additional Data on XLF Promoter Activity and Occupancy</p>
<p>Additional TGCA Analysis and Additional XLF levels in Melanocytes HCT116 cells</p>
<p>Additional Data for Patient Derived Melanoma Cells and Luciferase Reporter Assays</p>
<p>Additional Characterization of PTEN K128R</p>
<p>Additional Data on XLF Promoter Activity and Occupancy</p>
<p>Additional DNA Repair Data with PTEN-Complemented Cells</p>
<p>Additional TGCA Analysis and Additional XLF levels in Melanocytes HCT116 cells</p>
<p>Additional Data for Patient Derived Melanoma Cells and Luciferase Reporter Assays</p>