A5071942049- PARP inhibition in cancer therapy
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- DNA Repair Mechanisms
- Toxin Mechanisms and Immunotoxins
- Forensic Toxicology and Drug Analysis
- Advanced Proteomics Techniques and Applications
- Viral Infections and Immunology Research
- Neural dynamics and brain function
- Cancer-related Molecular Pathways
- Metabolomics and Mass Spectrometry Studies
- Retinal Development and Disorders
- Mass Spectrometry Techniques and Applications
- Cancer therapeutics and mechanisms
- Elasticity and Material Modeling
- Inflammasome and immune disorders
- Molecular Biology Techniques and Applications
- Integrated Circuits and Semiconductor Failure Analysis
- Neuroscience and Neuropharmacology Research
- Calcium signaling and nucleotide metabolism
- RNA Interference and Gene Delivery
Johns Hopkins University
2018-2025
Johns Hopkins Medicine
2024
Allen Institute for Brain Science
2018
DNA-protein cross-links (DPCs) are among the most detrimental genomic lesions. They ubiquitously produced by formaldehyde (FA), and failure to repair FA-induced DPCs blocks chromatin-based processes, leading neurodegeneration cancer. The type, structure, of remain largely unknown. Here, we profiled proteome found that flap endonuclease 1 (FEN1) resolves DPCs. We revealed FA also damages DNA bases adjoining DPCs, DPC-conjugated 5′ structures via base excision (BER) pathway. FEN1 repairs...
ADP-ribosylation, characterized by the addition of adenosine diphosphate ribose, can occur in both monomeric (MARylation) and polymeric (PARylation) forms. Little is known about specific contributions MARylation PARylation to cellular processes due a lack tools for jointly investigating these individual We present novel mass spectrometry (MS)-based proteomics approach that preserves information native ADP-ribosylation form associated with modification site within single experiment. Our...
The Lipidyzer platform was recently updated on a SCIEX QTRAP 6500+ mass spectrometer and offers targeted lipidomics assay including 1150 different lipids. We evaluated this approach using human plasma samples compared the results against global untargeted method high-resolution Q Exactive HF Orbitrap spectrometer.
PARP13/ZAP (zinc-finger antiviral protein) acts against multiple viruses by promoting degradation of viral mRNA. PARP13 has four N-terminal zinc (Zn) fingers that bind CG-rich nucleotide sequences, a C-terminal ADP ribosyltransferase fold, and central region with fifth Zn finger tandem WWE domains. The region, ZnF5-WWE1-WWE2, is implicated in binding poly(ADP-ribose); however, there are limited insights into its structure function. We present crystal structures ZnF5-WWE1-WWE2 from mouse...
Plasticity of thalamocortical (TC) synapses is robust during early development and becomes limited in the adult brain. We previously reported that a short duration deafening strengthens TC primary visual cortex (V1) mice. Here, we demonstrate restores NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) onto principal neurons V1 layer 4 (L4), which accompanied by an increase NMDAR function. In contrast, did not recover depression (LTD) at synapses. Potentiation absent...
Abstract DNA-protein crosslinks (DPCs) are among the most ubiquitous and detrimental DNA lesions which arise from exposure to metabolic stresses, drugs, or crosslinking agents such as formaldehyde (FA). FA is a cellular by-product of methanol metabolism, histone demethylation, lipid peroxidation well environmental pollutants. Failure repair FA-induced DPCs blocks nearly all chromatin-based processes including replication transcription, leading immunodeficiencies, neurodegeneration, cancer....
PARP1 (ARTD1) and Tankyrases (TNKS1/TNKS2; PARP5a/5b) are poly-ADP-ribose polymerases (PARPs) with catalytic non-catalytic functions that regulate both the genome proteome during zygotic activation (ZGA), totipotent, pluripotent embryonic stages. Here, we show primed, conventional human stem cells (hPSC) cultured continuously under non-specific TNKS1/TNKS2/PARP1-inhibited chemical naive reversion conditions underwent epigenetic reprogramming to clonal blastomere-like cells. TIRN concurrently...
SUMMARY ADP-ribosylation is a highly dynamic and fully reversible post-translational modification performed by poly(ADP-ribose) polymerases (PARPs) that modulates protein function, abundance, localization turnover. Here we show influenza A virus infection causes rapid dramatic upregulation of global inhibits viral replication. Mass spectrometry defined for the first time ADP-ribosylome during infection, creating an infection-specific profile with almost 4,300 sites on ∼1,080 host proteins,...
ABSTRACT PARP13/ZAP acts against multiple viruses through recognizing and promoting degradation of cytoplasmic viral mRNA. PARP13 has four N-terminal Zn-finger motifs that bind CG-rich nucleotide sequences, a C-terminal ADP ribosyltransferase fold similar to other PARPs. A central region predicted contain fifth two tandem WWE domains is implicated in binding poly(ADP-ribose); however, there are limited insights into the structure function this (ZnF5-WWE1-WWE2). Here, we present crystal...