A5020360537- DNA Repair Mechanisms
- Genetic factors in colorectal cancer
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- PARP inhibition in cancer therapy
- RNA modifications and cancer
- Chromatin Remodeling and Cancer
- Cancer Genomics and Diagnostics
- Cancer Mechanisms and Therapy
- Pancreatic and Hepatic Oncology Research
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- Integrated Circuits and Semiconductor Failure Analysis
- RNA Interference and Gene Delivery
- Advanced Welding Techniques Analysis
- Colorectal Cancer Treatments and Studies
- Sulfur Compounds in Biology
- Nanoparticles: synthesis and applications
- BRCA gene mutations in cancer
- Biotin and Related Studies
- Graphene and Nanomaterials Applications
- Calcium signaling and nucleotide metabolism
- Metabolomics and Mass Spectrometry Studies
- Cancer therapeutics and mechanisms
- Advanced Nanomaterials in Catalysis
Harvard University
2019-2025
University of Calgary
2017
Mount Royal University
2013
The emergence of drug resistance limits the efficacy targeted therapies in human tumors. prevalent view is that a fait accompli: when treatment initiated, cancers already contain drug-resistant mutant cells. Bacteria exposed to antibiotics transiently increase their mutation rates (adaptive mutability), thus improving likelihood survival. We investigated whether colorectal cancer (CRC) cells likewise exploit adaptive mutability evade therapeutic pressure. found epidermal growth factor...
Silver nanoparticles (AgNPs), owing to their effective antimicrobial properties, are being widely used in a broad range of applications. These include, but not limited to, antibacterial materials, the textile industry, cosmetics, coatings various household appliances and medical devices. Despite extensive use, little is known about AgNP safety toxicity vis-à-vis human animal health. Recent studies have drawn attention towards potential neurotoxic effects AgNPs, however, primary cellular...
Although mismatch repair (MMR) is essential for correcting DNA replication errors, it can also recognize other lesions, such as oxidized bases. In G0 and G1, MMR kept in check through unknown mechanisms error-prone during these cell cycle phases. We show that mammalian cells, D-type cyclins are recruited to sites of oxidative damage a PCNA- p21-dependent manner. inhibit the proteasomal degradation p21, which competes with proteins binding PCNA, thereby inhibiting MMR. The ability limit CDK4-...
Cell survival after oxidative DNA damage requires signaling, repair and transcriptional events often enabled by nucleosome displacement, exchange or removal chromatin remodeling enzymes. Here, we show that Chromodomain Helicase DNA-binding protein 6 (CHD6), distinct to other CHD enzymes, is stabilized during stress via reduced degradation. CHD6 relocates rapidly in a manner dependent upon lesions conserved N-terminal poly(ADP-ribose)-dependent recruitment motif, with later retention...
Non-homologous end joining (NHEJ) repairs DNA double strand breaks in non-cycling eukaryotic cells. NHEJ relies on polynucleotide kinase/phosphatase (PNKP), which generates 5΄-phosphate/3΄-hydroxyl termini that are critical for ligation by the ligase, LigIV. PNKP and LigIV require scaffolding protein, XRCC4. The FHA domain binds to CK2-phosphorylated XRCC4 C-terminal tail, while uses its tandem BRCT repeats bind coiled-coil. Yet, assembled PNKP-XRCC4-LigIV complex remains uncharacterized....
Glioblastoma (GBM) has a poor prognosis despite intensive treatment with surgery and chemoradiotherapy. Previous studies using dose-escalated radiotherapy have demonstrated improved survival; however, increased rates of radionecrosis limited its use. Development radiosensitizers could improve patient outcome. In the present study, we report use sodium sulfide (Na2S), hydrogen (H2S) donor, to selectively kill GBM cells (T98G U87) while sparing normal human cerebral microvascular endothelial...
Background: The lack of molecular targets for triple negative breast cancer (TNBC) has limited treatment options and reduced survivorship. Identifying new may help improve patient survival decrease recurrence metastasis. As DNA repair defects are prevalent in cancer, we evaluated the expression capacities proteins preclinical models. Methods: capacity was analyzed four TNBC cell lines, MDA-MB-157 (MDA-157), MDA-MB-231 (MDA-231), MDA-MB-468 (MDA-468), HCC1806, using fluorescence multiplex...
DNA repair defects have been increasingly focused on as therapeutic targets. In hormone-positive breast cancer, XRCC1-deficient tumors identified and proposed targets for combination therapies that damage inhibit pathways. XRCC1 is a scaffold protein functions in base excision (BER) by mediating essential interactions between glycosylases, AP endonuclease, poly(ADP-ribose) polymerase 1, β (POL β), ligases. Loss of confers BER hypersensitivity to damaging agents. not evaluated triple negative...
To tolerate oxidative stress, cells enable DNA repair responses often sensitive to poly(ADP-ribose) (PAR) polymerase 1 and 2 (PARP1/2) inhibition—an intervention effective against cancers lacking BRCA1/2. Here, we demonstrate that mutating the CHD6 chromatin remodeler sensitizes PARP1/2 inhibitors in a manner distinct from BRCA1, recruitment damage requires cooperation between PAR- DNA-binding domains essential for nucleosome sliding activity. displays direct PAR-binding, interacts with...
Background & Aims: ARID1A is postulated to be a tumor suppressor gene owing loss-of-function mutations in human pancreatic ductal adenocarcinomas (PDAC). However, its role pathogenesis not clear despite recent studies using genetically engineered mouse (GEM) models. We aimed at further understanding of direct functional PDAC, combination GEM model and PDAC cell lines. Methods: Pancreas-specific mutant Arid1a-driven (Ptf1a-Cre; KrasG12D; Arid1af/f or "KAC") was generated by crossing...
Abstract DNA repair defects have been increasingly focused on as therapeutic targets. In hormone positive breast cancer, XRCC1-deficient tumors identified and proposed targets for combination therapies that damage inhibit pathways. XRCC1 is a scaffold protein functions in base excision (BER) by mediating essential interactions between glycosylases, AP endonuclease, poly(ADP-ribose) polymerase 1, β (POL β), ligases. Loss of confers BER hypersensitivity to damaging agents. not evaluated triple...
ABSTRACT The large majority of oxidative DNA lesions occurring in the G1 phase cell cycle are repaired by base excision repair (BER) rather than mismatch (MMR) to avoid long resections that can lead genomic instability and death. However, molecular mechanisms dictating pathway choice between MMR BER have remained unknown. Here, we show that, during G1, D-type cyclins recruited sites damage a PCNA- p21-dependent manner. shield p21 from its two ubiquitin ligases CRL1 SKP2 CRL4 CDT2...
Rev7 is a regulatory protein with roles in translesion synthesis (TLS), double strand break (DSB) repair, replication fork protection, and cell cycle regulation. forms homodimer vitro using its HORMA (Hop, Rev7, Mad2) domain; however, the functional importance of dimerization has been incompletely understood. We analyzed properties cells expressing either wild-type mouse or Rev7K44A/R124A/A135D, mutant that cannot dimerize. The expression but not mutant, rescued sensitivity Rev7−/− to X-rays...
Abstract Background & Aims ARID1A is postulated to be a tumor suppressor gene owing loss-of-function mutations in human pancreatic ductal adenocarcinomas (PDAC). However, its role pathogenesis not clear despite recent studies using genetically engineered mouse (GEM) models. We aimed at further understanding of direct functional PDAC, combination GEM model, PDAC cell lines. Methods Pancreas-specific mutant Arid1a -driven model ( Ptf1a -Cre; Kras G12D ; f/f or “KAC”) was generated by...
Abstract Success in eradicating human cancer with targeted therapies is limited by the emergence of secondary resistance. The prevalent view that resistance a fait accompli: when treatment initiated, tumors already contain drug-resistant mutant cells. However, cells are challenged agents, drug tolerant ‘persister’ cell population often observed. Persisters survive exposure to through non-genetic, poorly understood mechanisms, and constitute reservoir from which genetically divergent,...