A5029848713- DNA Repair Mechanisms
- Sirtuins and Resveratrol in Medicine
- Mitochondrial Function and Pathology
- Genomics and Chromatin Dynamics
- Calcium signaling and nucleotide metabolism
- Adipose Tissue and Metabolism
- Autophagy in Disease and Therapy
- CRISPR and Genetic Engineering
- Phosphodiesterase function and regulation
- Peptidase Inhibition and Analysis
- Genetics, Aging, and Longevity in Model Organisms
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- 3D Printing in Biomedical Research
- Hemoglobinopathies and Related Disorders
- BRCA gene mutations in cancer
- Retinoids in leukemia and cellular processes
- Cancer-related Molecular Pathways
- Inflammasome and immune disorders
- Microtubule and mitosis dynamics
- PARP inhibition in cancer therapy
- Histone Deacetylase Inhibitors Research
- Metabolism, Diabetes, and Cancer
- Chromatin Remodeling and Cancer
- interferon and immune responses
National Heart Lung and Blood Institute
2015-2025
Pfizer (United States)
2021-2025
National Institutes of Health
2013-2023
National Institute of Diabetes and Digestive and Kidney Diseases
1996-2019
ProQuest (United States)
2019
Bioengineering Center
2019
Génétique et biologie du développement
2012-2013
Institut thématique Génétique, génomique et bioinformatique
2012
Howard Hughes Medical Institute
1987-1999
MRC Laboratory of Molecular Biology
1993
Resveratrol, a natural polyphenolic compound that is found in grapes and red wine, increases metabolic rate, insulin sensitivity, mitochondrial biogenesis, physical endurance reduces fat accumulation mice. Although it thought resveratrol targets Sirt1, this controversial because also activates 5' AMP-activated protein kinase (AMPK), which regulates sensitivity biogenesis. Here, we use mice deficient AMPKalpha1 or -alpha2 to determine whether the effects of are mediated by AMPK.Mice catalytic...
Mitochondrial stress releases mitochondrial DNA (mtDNA) into the cytosol, thereby triggering type Ι interferon (IFN) response. outer membrane permeabilization, which is required for mtDNA release, has been extensively studied in apoptotic cells, but little known about its role live cells. We found that oxidatively stressed mitochondria release short fragments via pores formed by voltage-dependent anion channel (VDAC) oligomers membrane. Furthermore, positively charged residues N-terminal...
Insulators, first identified in Drosophila , are DNA sequence elements that shield a promoter from nearby regulatory elements. We have previously reported at the 5′ end of chicken β-globin locus can function as an insulator. It is capable shielding reporter gene activating effects mouse control region element human erythroleukemic cell line K562. In this report, we show most insulating activity lies 250-bp CpG island (core element), which contains constitutive DNase I-hypersensitive site...
The pathway determining malignant cellular transformation, which depends upon mutation of the BRCA1 tumor suppressor gene, is poorly defined. A growing body evidence suggests that promotion DNA double-strand break repair by homologous recombination (HR) may be means maintains genomic stability, while a role in error-prone nonhomologous (NHR) processes has just begun to elucidated. protein becomes phosphorylated response damage, but effects phosphorylation on recombinational are unknown. In...
Checkpoints maintain the order and fidelity of eukaryotic cell cycle, defects in checkpoints contribute to genetic instability cancer. Much our current understanding comes from studies conducted yeast. In fission yeast Schizosaccharomyces pombe (Sp), SpRad3 is an essential component both DNA damage replication checkpoints. The SpChk1 SpCds1 protein kinases function downstream SpRad3. effector checkpoint and, absence SpCds1, serves checkpoint. functions S phase Human homologs but not have...
The circadian clock synchronizes the activity level of an organism to light-dark cycle environment. Energy intake, as well energy metabolism, also has a diurnal rhythm. Although role genes in sleep-wake is characterized, their generation metabolic rhythms poorly understood. Here, we use mice deficient protein mPer2 study how regulates two critical rhythms: glucocorticoid and food intake rhythms. Our findings indicate that mPer2−/− do not have rhythm even though corticosterone response...
Metformin is one of the most commonly used first line drugs for type II diabetes. lowers serum glucose levels by activating 5'-AMP-activated kinase (AMPK), which maintains energy homeostasis directly sensing AMP/ATP ratio. AMPK plays a central role in food intake and metabolism through its activities nervous system peripheral tissues. Since synchronized to light-dark (LD) cycle environment, we investigated possibility that may affect circadian rhythm. We discovered period Rat-1 fibroblasts...
Background AMP protein kinase (AMPK) plays an important role in food intake and energy metabolism, which are synchronized to the light-dark cycle. In vitro, AMPK affects circadian rhythm by regulating at least two clock components, CKIα CRY1, via direct phosphorylation. However, it is not known whether catalytic activity of actually regulates vivo. Methodology/Principal Finding The subunit has isoforms: α1 α2. We investigate behavior, physiology gene expression AMPKα1−/− AMPKα2−/− mice....
Recent studies have implicated mitochondrial dysfunction as a trigger of inflammatory bowel diseases, including Crohn's disease (CD) and ulcerative colitis (UC). We investigated the role mitochondria gate-keeper protein, voltage-dependent-anion channel 1 (VDAC1), in gastrointestinal inflammation tested effects newly developed VDAC1-interacting molecules, VBIT-4 VBIT-12, on UC induced by dextran sulfate sodium (DSS) or trinitrobenzene sulphonic acid (TNBS) mice. VDAC1, which controls...
hCds1 (Chk2) (1-4) is an evolutionarily conserved kinase that functions in DNA damage response and cell cycle checkpoint. The Cds1 family of kinases are activated by a large phosphatidylinositol 3-kinase-like kinases. In humans, ataxia telangiectasia-mutated (ATM) (5) ataxia-telangiectasia Rad3-related (6) activate phosphorylating Thr<sup>68</sup> (7-9). Cds1-related contain the FHA (forkhead-associated) domain (10), which appears to be important for integrating signal. It not known how ATM...
Mammalian Chk1 and Chk2 are two Ser/Thr effector kinases that play critical roles in DNA damage-activated cell cycle checkpoint signaling pathways downstream of ataxia telangiectasia-mutated telangiectasia-related. Endogenous substrates have been identified for human hCds1/Chk2 Chk1; however, the sequences surrounding substrate residues appear unrelated, consensus motifs remain unknown. We utilized peptide library analyses to develop specific, highly preferred Chk1. The optimal similar both...
SIRT1, an NAD+ (nicotinamide adenine dinucleotide)-dependent deacetylase, protects cells from stress-induced apoptosis, and its orthologues delay aging in lower eukaryotes. SIRT1 increases survival response to stress such as DNA damage by deacetylating a number of substrates including pro-apoptotic protein p53. The molecular mechanism which DNA-damage activates is not known. By screening kinase inhibitor library, we identified CK2 kinase. pleiotropic with more than 300 well-known...
Abstract The tumor suppressor gene BRCA1 maintains genomic integrity by protecting cells from the deleterious effects of DNA double-strand breaks (DSBs). Through its interactions with checkpoint kinase 2 (Chk2) and Rad51, promotes homologous recombination, which is typically an error-free repair process. In addition, accumulating evidence implicates in regulation nonhomologous end-joining (NHEJ), may involve precise religation DSB ends if they are compatible (i.e., repair) or sequence...
Abstract Epigenetic factors have been suggested to play an important role in metabolic memory by trapping and maintaining initial changes within the transcriptional regulatory machinery. In this study we fed mice a high fat diet (HFD) for seven weeks followed additional five of chow, identify HFD-mediated hepatic program that may persist after weight loss. Mice HFD displayed increased fasting insulin levels, hepatosteatosis major gene transcription associated with modulation H3K27Ac at...