A5077467093- DNA Repair Mechanisms
- Mitochondrial Function and Pathology
- Asthma and respiratory diseases
- Allergic Rhinitis and Sensitization
- Cytomegalovirus and herpesvirus research
- Immune Response and Inflammation
- Fungal and yeast genetics research
- Adipose Tissue and Metabolism
- DNA and Nucleic Acid Chemistry
- Genetic Neurodegenerative Diseases
- Carcinogens and Genotoxicity Assessment
- Immune Cell Function and Interaction
- Pediatric health and respiratory diseases
- Epigenetics and DNA Methylation
- NF-κB Signaling Pathways
- Neonatal Respiratory Health Research
- Sirtuins and Resveratrol in Medicine
- RNA Research and Splicing
- Herpesvirus Infections and Treatments
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Cell death mechanisms and regulation
- Cytokine Signaling Pathways and Interactions
- Genomics, phytochemicals, and oxidative stress
- Virus-based gene therapy research
The University of Texas Medical Branch at Galveston
2016-2025
Columbia University
2013-2023
Columbia University Irving Medical Center
2009-2023
University of Exeter
2022
Shanghai Jiao Tong University
2022
Keio University
2022
Estación Experimental del Zaidín
2022
Sanford Burnham Prebys Medical Discovery Institute
2022
Western University
2001-2022
National Centre for Biological Sciences
2022
8-oxoguanine (8-oxoG), ring-opened purines (formamidopyrimidines or Fapys), and other oxidized DNA base lesions generated by reactive oxygen species are often mutagenic toxic, have been implicated in the etiology of many diseases, including cancer, aging. Repair these all organisms occurs primarily via excision repair pathway, initiated with their glycosylase/AP lyases, which two classes. One class utilizes an internal Lys residue as active site nucleophile, includes Escherichia coli Nth...
Apurinic/apyrimidinic (AP) endonuclease (APE; EC 4.2.99.18 ) plays a central role in repair of DNA damage due to reactive oxygen species (ROS) because its 3′-phosphoesterase activity removes 3′ blocking groups that are generated by glycosylase/AP-lyases during removal oxidized bases and direct ROS reaction with DNA. The major human APE (APE-1) gene is activated selectively sublethal levels variety generators, including ionizing radiation, but not other genotoxicants—e.g., UV light alkylating...
Pollen exposure induces allergic airway inflammation in sensitized subjects. The role of antigenic pollen proteins the induction is well characterized, but contribution other constituents grains to this process unknown. Here we show that and their extracts contain intrinsic NADPH oxidases. oxidases rapidly increased levels ROS lung epithelium as amount oxidized glutathione (GSSG) 4-hydroxynonenal (4-HNE) airway-lining fluid. These oxidases, products oxidative stress (such GSSG 4-HNE)...
Significance Amyotrophic lateral sclerosis (ALS) is a devastating, motor neuron degenerative disease without any cure to date. About 95% of ALS patients feature abnormalities in the RNA/DNA binding protein TDP-43, involving its nucleus-cytoplasmic mislocalization spinal neurons. How TDP-43 pathology triggers neuronal apoptosis remains unclear. Here, we report that participates DNA damage response and nuclear clearance neurons causes double-strand break repair defects ALS. Our findings...
The onset of inflammation is associated with reactive oxygen species and oxidative damage to macromolecules like 7,8-dihydro-8-oxoguanine (8-oxoG) in DNA. Because 8-oxoguanine DNA glycosylase 1 (OGG1) binds 8-oxoG because Ogg1-deficient mice are resistant acute systemic inflammation, we hypothesized that OGG1 inhibition may represent a strategy for the prevention treatment inflammation. We developed TH5487, selective active-site inhibitor OGG1, which hampers binding repair well tolerated by...
Abstract Interstitial lung diseases such as idiopathic pulmonary fibrosis (IPF) are caused by persistent micro-injuries to alveolar epithelial tissues accompanied aberrant repair processes. IPF is currently treated with pirfenidone and nintedanib, compounds which slow the rate of disease progression but fail target underlying pathophysiological mechanisms. The DNA protein 8-oxoguanine glycosylase-1 (OGG1) has significant roles in modulation inflammation metabolic syndromes. Currently, no...
Two candidate human orthologs of<i>Escherichia coli</i> MutM/Nei were recently identified in the genome database, and one of these, NEH1, was characterized earlier (Hazra, T. K., Izumi, T., Boldogh, I., Imhoff, B., Kow, Y. W., Jaruga, P., Dizdaroglu, M. (2002) <i>Proc. Natl. Acad. Sci. U. S. A.</i> 99, 3523–3528). Here we report characterization second protein, originally named NEH2 now renamed NEIL2 (Nei-like). The 37-kDa wild-type expressed purified from <i>E. has DNA glycosylase/AP lyase...
Previous studies indicate that two proteins, Mmm1p and Mdm10p, are required to link mitochondria the actin cytoskeleton of yeast for actin-based control mitochondrial movement, inheritance morphology. Both proteins integral outer membrane proteins. localizes punctate structures in close proximity DNA (mtDNA) nucleoids. We found Mdm10p exist a complex with Mdm12p, another protein morphology inheritance. This interpretation is based on observations 1) Mdm12p showed same localization as Mmm1p;...
The cytokine tumor necrosis factor α (TNF-α) induces expression of inflammatory gene networks by activating cytoplasmic to nuclear translocation the factor-κB (NF-κB) transcription factor. NF-κB activation results from sequential phosphorylation and hydrolysis inhibitor, IκBα, through 26 S proteasome. Here, we show a parallel proteasome-independent pathway for cytokine-inducible IκBα proteolysis in HepG2 liver cells mediated cytosolic calcium-activated neutral protease (calpains)....
Abstract The prevalence of allergies and asthma among the world’s population has been steadily increasing due to environmental factors. It described that exposure ozone, diesel exhaust particles, or tobacco smoke exacerbates allergic inflammation in lungs. These oxidants increase levels cellular reactive oxygen species (ROS) induce mitochondrial dysfunction airway epithelium. In this study, we investigated involvement preexisting exacerbation inflammation. After oxidative insult induced by...
The human endonuclease III (hNTH1), a homolog of the <i>Escherichia coli</i> enzyme (Nth), is DNA glycosylase with abasic (apurinic/apyrimidinic (AP)) lyase activity and specifically cleaves oxidatively damaged pyrimidines in DNA. Its cDNA was cloned, full-length (304 amino acid residues) expressed as glutathione <i>S</i>-transferase fusion polypeptide <i>E. coli</i>. Purified wild-type protein two additional residues truncated deletion 22 at NH<sub>2</sub> terminus were equally active had...