A5046046671- DNA Repair Mechanisms
- Telomeres, Telomerase, and Senescence
- Epigenetics and DNA Methylation
- Mitochondrial Function and Pathology
- Genomics and Chromatin Dynamics
- PARP inhibition in cancer therapy
- Genetic Neurodegenerative Diseases
- Genetics, Aging, and Longevity in Model Organisms
- Cancer-related Molecular Pathways
- Muscle Physiology and Disorders
- Advanced biosensing and bioanalysis techniques
- Amyotrophic Lateral Sclerosis Research
- Cancer Cells and Metastasis
- DNA and Nucleic Acid Chemistry
- CRISPR and Genetic Engineering
- FOXO transcription factor regulation
- MicroRNA in disease regulation
- RNA Research and Splicing
- Histone Deacetylase Inhibitors Research
- RNA and protein synthesis mechanisms
- Circular RNAs in diseases
- RNA modifications and cancer
UPMC Hillman Cancer Center
2020-2025
University of Pittsburgh
2020-2023
University of Pittsburgh Medical Center
2020
Institute for Experimental Endocrinology and Oncology
2020
University of Naples Federico II
2018-2019
Federico II University Hospital
2018
European School of Molecular Medicine
2013
Abstract Oxidative stress is a primary cause of cellular senescence and contributes to the etiology numerous human diseases. damage telomeric DNA has been proposed premature by accelerating telomere shortening. Here, we tested this model directly using precision chemoptogenetic tool produce common lesion 8-oxo-guanine (8oxoG) exclusively at telomeres in fibroblasts epithelial cells. A single induction 8oxoG sufficient trigger multiple hallmarks p53-dependent senescence. Telomeric activates...
Abstract Telomeres are hypersensitive to the formation of common oxidative lesion 8-oxoguanine (8oxoG), which impacts telomere stability and function. OGG1 MUTYH glycosylases initiate base excision repair (BER) remove 8oxoG or prevent mutation. Here, we show loss inhibition, loss, partially rescues telomeric 8oxoG-induced premature senescence associated proinflammatory responses, while both causes a near complete rescue in human fibroblasts. Glycosylase deficiency also suppresses fragility...
Patricia L. Opresko1,2,3, Samantha Sanford3 and Mariarosaria De Rosa3 1Department of Pharmacology Chemical Biology, University Pittsburgh School Medicine, Pittsburgh, Pennsylvania 15261, USA 2Department Environmental Occupational Health, Public 3UPMC Hillman Cancer Center at the 15232, Correspondence: plo4{at}pitt.edu
Easily accessible biomarkers in Huntington disease (HD) are actively searched. We investigated telomere length and DNA double‐strand breaks (histone variant pγ‐H2AX) as predictive peripheral blood mononuclear cells (PBMC) from 25 premanifest subjects, 58 HD patients with similar CAG expansion the huntingtin gene ( HTT ), 44 healthy controls (HC). PBMC pre‐HD groups showed shorter telomeres p < 0.0001) a significant increase of pγ‐H2AX compared to 0.0001). The levels correlated robustly...
The epithelial-to-mesenchymal transition (EMT) is a complex transcriptional program induced by transforming growth factor β1 (TGF-β1). Histone lysine-specific demethylase 1 (LSD1) has been recognized as key mediator of EMT in cancer cells, but the precise mechanism that underlies activation and repression genes still remains elusive. Here, we characterized early events TGF-β1 during initiation establishment. triggered, 30-90 min post-treatment, nuclear oxidative wave throughout genome,...
Abstract We show that transcription induced by nuclear receptors for estrogen (E 2 ) or retinoic acid (RA) is associated with formation of chromatin loops juxtapose the 5’ end (containing promoter) enhancer and 3′ polyA addition site target gene. find three loop configurations which change as a function time after induction: 1. RA E -induced connect 5′ end, gene, are stabilized RNA early induction; 2. -independent whose stability does not require RNA; 3. Loops detected only treatment RNAse...
Tumor suppressor genes in the CDKN2A/B locus (p15INK4b, p16INK4a, and p14ARF) function as biological barriers to transformation are most frequently silenced or deleted human cancers. This gene silencing occurs due DNA methylation of promoter regions, although underlying mechanism is currently unknown. We present evidence that p16INK4a associated with damage caused by interference between transcription replication processes. Inhibition significantly reduces CpGs promoter. conclude de novo...
The human DNA base excision repair enzyme MUTYH (MutY homolog glycosylase) excises undamaged adenine that has been misincorporated opposite the oxidatively damaged 8-oxoG, preventing transversion mutations and serving as an important defense against deleterious effects of this damage. Mutations in gene predispose patients to MUTYH-associated polyposis colorectal cancer, expression documented a biomarker for pancreatic cancer. Measuring activity is therefore critical evaluating diagnosing...
Telomeres are prone to formation of the common oxidative lesion 8-oxoguanine (8oxoG), and acute production 8oxoG damage at telomeres is sufficient drive rapid cellular senescence. OGG1 MUTYH glycosylases initiate base excision repair (BER) sites remove or prevent mutation. Here, we show loss inhibition, loss, partially rescues telomeric 8oxoG-induced senescence, both results in a near complete rescue. Loss these also suppresses telomere fragility dysfunction, indicating that single-stranded...
Histone deacetylase inhibitors (HDACis) are anticancer agents that inhibit tumor cell growth and/or survival. However, their mechanism of action remains largely undefined. Recently, we have demonstrated HDACis induce apoptosis in a model rat thyroid cells transformed by the v-ras-Ki oncogene (FRTL-5 v-ras-Ki). The stabilization TNF-related apoptosis-inducing ligand (TRAIL) protein, due to its reduced ubiquitination and proteasome degradation, accounts for apoptotic effect induced...
SUMMARY Oxidative stress is a primary cause of cellular senescence and contributes to the pathogenesis numerous human diseases. damage telomeric DNA proposed trigger premature by accelerating telomere shortening. Here we tested this model directly using precision tool produce common base lesion 8-oxo-guanine (8oxoG) exclusively at telomeres in fibroblast epithelial cells. A single induction 8oxoG sufficient multiple hallmarks p53-dependent senescence. Telomeric activates ATM ATR signaling,...
Estrogen-induced transcription is characterized by localized histone demethylation and DNA oxidation, followed the recruitment of repair methyl-transferase enzymes at target sites. The functional link between these different proteins recruited estrogen chromatin sites unclear it unknown which steps catalyzed are essential for productive estrogen-mediated transcription. Here we report that specific genomic regions synchronously recruit receptor complexed with demethylase LSD1 protein such as...
Background: Blood biomarkers, that may improve the management of pre−manifest phase Huntington's disease (PRE−HD), are actively searched. We investigated telomere length (TL) and DNA damage signatures (DDS) as potential predictive biomarkers in peripheral blood mononuclear cells (PBMC) PRE−HD HD patients.