A5012117569- DNA Repair Mechanisms
- PARP inhibition in cancer therapy
- CRISPR and Genetic Engineering
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Sirtuins and Resveratrol in Medicine
- Cancer-related Molecular Pathways
- Pulmonary Hypertension Research and Treatments
- RNA Research and Splicing
- HIV/AIDS drug development and treatment
- Microtubule and mitosis dynamics
- MicroRNA in disease regulation
- Adenosine and Purinergic Signaling
- Transgenic Plants and Applications
- Biochemical and Molecular Research
- Yeasts and Rust Fungi Studies
- Adolescent and Pediatric Healthcare
- Cancer, Hypoxia, and Metabolism
- Family Support in Illness
- Genetics and Neurodevelopmental Disorders
- Renal and related cancers
- Calcium signaling and nucleotide metabolism
- Bacteriophages and microbial interactions
- Berry genetics and cultivation research
- Plant Virus Research Studies
University of South Alabama
2006-2024
USA Mitchell Cancer Institute
2016-2023
Mayo Clinic in Arizona
2022
Bainbridge State College
2014
NanoVector (United States)
2010
North Carolina State University
2010
Abstract Changes in nicotinamide adenine dinucleotide (NAD + ) levels that compromise mitochondrial function trigger release of DNA damaging reactive oxygen species. NAD also affect repair capacity as is a substrate for PARP-enzymes (mono/poly-ADP-ribosylation) and sirtuins (deacetylation). The ecto-5′-nucleotidase CD73, an ectoenzyme highly expressed cancer, suggested to regulate intracellular by processing its bio-precursor, mononucleotide (NMN), from tumor microenvironments, thereby...
Assembly and disassembly of DNA repair protein complexes at damage sites are essential for maintaining genomic integrity. Investigating factors coordinating assembly the base excision (BER) proteins polymerase β (Polβ) XRCC1 to lesion identifies a role Polβ in regulating from and, conversely, demonstrates Polβ's dependence on complex assembly. LivePAR, genetically encoded probe live-cell imaging poly(ADP-ribose) (PAR), reveals that require PAR repair-complex assembly, with PARP1 PARP2...
Multifunctional nanoparticles hold promise as the next generation of therapeutic delivery and imaging agents. Nanoparticles comprising many types materials are being tested for this purpose, including plant viral capsids. It has been found that Red clover necrotic mosaic virus (RCNMV) can be loaded with significant amounts molecules molecular weights 600 or even greater. Formulation RCNMV into a nanoparticle (PVN) involves loading cargo attachment peptides. In study, we show targeting...
Pulmonary microvascular endothelial cells (PMVECs) are enriched with progenitor that underlie their rapid proliferation and vasculogenic capacity. However, the molecular basis for such an enhanced growth potential is unknown. Nucleosome assembly protein-1 (NAP1), its related family of proteins, have been incriminated in control cell a range species. We therefore sought to determine whether NAP1 contributes vasculogenesis observed PMVECs. was expressed at high level two fast-growing types,...
Abstract Protein–protein interactions regulate many essential enzymatic processes in the cell. Somatic mutations outside of an enzyme active site can therefore impact cellular function by disruption critical protein–protein interactions. In our investigation T304I cancer mutation DNA Polymerase β (Polβ), we find that this surface threonine residue impacts Polβ We show proteasome-mediated degradation is regulated both ubiquitin-dependent and ubiquitin-independent via unique The proteasome...
Abstract Elevated expression of the DNA damage response proteins PARP1 and poly(ADP-ribose) glycohydrolase (PARG) in glioma stem cells (GSCs) suggests that may be a unique target for PARG inhibitors (PARGi). While PARGi-induced cell death is achieved when combined with ionizing radiation, as single agent appear to mostly cytostatic. Supplementation NAD+ precursor dihydronicotinamide riboside (NRH) rapidly increased levels GSCs cells, inducing activation mild suppression replication fork...
The ability to quickly discover reliable hits from screening and rapidly convert them into lead compounds, which can be verified in functional assays, is central drug discovery. expedited validation of novel targets the identification modulators advance preclinical studies significantly increase development success. Our SaXPyTM (“SAR by X-ray Poses Quickly”) platform, applicable any crystallography-enabled target, couples established methods protein crystallography fragment-based discovery...
EGFR signaling has been implicated in hypoxia-associated resistance to radiation or chemotherapy. Non-small cell lung carcinomas (NSCLC) with activating L858R ΔE746-E750 mutations exhibit elevated activity and downstream signaling. Here, relative wild-type (WT) EGFR, mutant (MT) expression significantly increases radiosensitivity hypoxic cells. Gene profiling human bronchial epithelial cells (HBEC) revealed that MT-EGFR transcripts related cycle replication aerobic conditions downregulated...
Children with rare or life-limiting chronic conditions and their families are at high risk of psychosocial distress. However, despite its impact on patient family health functioning, distress antecedents may not routinely be captured in medical records. The purpose this study was to characterize current record documentation practices around among children families. Medical records for patients (n = 60) followed by a pediatric complex care program were reviewed. Study team members extracted...
Abstract Traditional rust preventives utilize waxes, metal sulfonates and oils to leave a thin, temporary coating on surface. Ongoing research has started design preventive formulations that provide more robust corrosion protection utilizes new alternative chemistries. This study will compare technology componentry the traditional preventives. examine differences in performance, physical characteristics solubility profiles.
Abstract PARP-inhibitors (PARPi) have been developed to treat homology-directed repair deficient cancers such as BRCA1/2-defective breast and ovarian tumors. However, acquired resistance PARPi is now common, suggesting the need identify new protein targets. To that end, a missed opportunity found in PARP1/PARP2 activation mechanism response DNA damage replication stress resulting complexes enzymes depend on coordinate PARP-mediated processes. We activation, whether from acute damage, or both...
The multitude of DNA lesion types, and the nuclear dynamic context in which they occur, present a challenge for genome integrity maintenance as this requires engagement different repair pathways. Specific 'repair controllers' that facilitate pathway crosstalk between double strand break (DSB) base excision (BER), regulate BER protein trafficking at sites, have yet to be identified. We find polymerase β (Polβ), crucial BER, is ubiquitylated complex-dependent manner by TRIP12, an E3 ligase...
Nucleosome assembly protein (NAP) is a chromatin-associated that fulfills an important role in cell memory, and has been incriminated the control of growth. We have recently shown NAP expression determinant endothelial vasculogenic phenotype. Western analysis using monoclonal antibody specifically targeting 4a8 epitope consistently resolved two bands. The higher molecular weight band 58 kD, corresponds to full length NAP. lower 53 postulated be degradation product, although this yet...
SUMMARY Assembly and disassembly of DNA repair protein complexes at sites damage is essential to maintain genomic integrity. We investigated factors coordinating assembly the base excision (BER) proteins, polymerase β (Polβ) XRCC1, lesion sites, identifying a new role for Polβ in regulating XRCC1 from conversely, demonstrating Polβ’s dependence on complex assembly. RealPAR, genetically-encoded probe live cell imaging poly(ADP-ribose) (PAR), reveals that require PAR degradation disassembly....
Abstract Traditional rust preventives utilize wax and oils to leave a thin, temporary coating on metal surface. The waxes used in traditional are petroleum typically from Group I refineries. Ongoing research has started investigating alternative such as natural synthetic waxes. Because these have varying melt point structures comparison waxes, solubilizer is needed. This study will compare made with the preventives. also examine differences performance of without solubilizers.
<p>Ectopic MT-EGFR expression significantly reduces hypoxia-associated radiation resistance in A549 NSCLC cells.</p>
Nucleosome assembly protein (NAP) has a role in inducing pro-proliferative phenotype all cells during development and several cell types the adult including hematopoetic precursors. Pulmonary microvascular endothelial (PMVECs) proliferate rapidly when isolated grown culture compared to pulmonary artery (PAECs). mRNA analysis revealed PMVECs produce 3.5 fold greater NAP than PAECs. We hypothesize PMVEC is maintained by NAP. overexpressing PAECs using retroviral transfection induction of...
The multitude of DNA lesion types, and the nuclear dynamic context in which they occur, present a challenge for genome integrity maintenance as this requires engagement different repair pathways. Specific ‘repair controllers’ that facilitate pathway crosstalk at sites, by regulating base excision (BER) protein trafficking, have yet to be identified. We find polymerase β (Polβ), crucial BER, is ubiquitylated BER complex-dependent manner TRIP12, an E3 ligase partnered with UBR5 restrains...