A5043500292- Mass Spectrometry Techniques and Applications
- Advanced Proteomics Techniques and Applications
- Cardiac Fibrosis and Remodeling
- Monoclonal and Polyclonal Antibodies Research
- Vitamin K Research Studies
- Microtubule and mitosis dynamics
- Cellular transport and secretion
- Ubiquitin and proteasome pathways
- Metabolomics and Mass Spectrometry Studies
- Protein Degradation and Inhibitors
- interferon and immune responses
- Muscle Physiology and Disorders
- Influenza Virus Research Studies
- Advanced Biosensing Techniques and Applications
- Cardiomyopathy and Myosin Studies
- Respiratory viral infections research
- Chronic Lymphocytic Leukemia Research
- HER2/EGFR in Cancer Research
- Histone Deacetylase Inhibitors Research
- HIV Research and Treatment
- Peptidase Inhibition and Analysis
- vaccines and immunoinformatics approaches
- Parkinson's Disease Mechanisms and Treatments
- Glycosylation and Glycoproteins Research
- Genetic and Kidney Cyst Diseases
AbbVie (United States)
2018-2025
University of Wisconsin–Madison
2013-2023
Energy Center of Wisconsin
2016-2019
Thermo Fisher Scientific (United States)
2017
University of Illinois Urbana-Champaign
2011
Mechanical signals play a critical role in the regulation of muscle mass, but molecules that sense mechanical and convert this stimulus into biochemical events regulate mass remain ill-defined. Here we report spectrometry-based workflow to study changes protein phosphorylation occur mouse skeletal 1 h after bout electrically evoked maximal-intensity contractions (MICs). Our dataset provides first comprehensive map MIC-regulated phosphoproteome. Using unbiased bioinformatics approaches,...
Influenza virus expresses transcripts early in infection and transitions towards genome replication at later time points. This process requires de novo assembly of the viral machinery, large ribonucleoprotein complexes (RNPs) composed polymerase, genomic RNA oligomeric nucleoprotein (NP). Despite central role RNPs during infection, factors dictating where when they assemble are poorly understood. Here we demonstrate that human protein kinase C (PKC) family members regulate RNP assembly....
Mechanical signals, such as those evoked by maximal-intensity contractions (MICs), can induce an increase in muscle mass. Rapamycin-sensitive signaling events are widely implicated the regulation of this process; however, recent studies indicate that rapamycin-insensitive also involved. Thus, to identify these events, we generate a map MIC-regulated and rapamycin-sensitive phosphoproteome. In total, quantify more than 10,000 unique phosphorylation sites find 2,000 significantly affected...
Targeted protein degradation (TPD) is a therapeutic approach that leverages the cell's natural machinery to degrade targets instead of inhibiting them. This accomplished by using mono- or bifunctional small molecules designed induce proximity target proteins and E3 ubiquitin ligases, leading ubiquitination subsequent proteasome-dependent target. One most significant attributes TPD its proposed catalytic mechanism action, which permits substoichiometric exposure achieve desired...
Negative-sense RNA viruses assemble large ribonucleoprotein (RNP) complexes that direct replication and transcription of the viral genome. Influenza virus RNPs contain polymerase, genomic multiple copies nucleoprotein (NP). During RNP assembly, monomeric NP oligomerizes along length RNA. Regulated assembly is essential for replication, but how maintained as a monomer subsequently to form poorly understood. Here we elucidate mechanism whereby phosphorylation regulates oligomerization. We...
Peptides presented by the class-I major histocompatibility complex (MHC-I) are important targets for immunotherapy. The identification of these peptide greatly facilitates generation T-cell-based therapeutics. Herein, we report capability proteolysis targeting chimera (PROTAC) compounds to induce presentation specific MHC peptides derived from endogenous cellular proteins. Using LC-MS/MS, identified several BET-derived MHC-I induced treatment with three BET-directed PROTAC compounds. To...
Methods for the generation of substratespresenting biomolecules in a spatially controlled manner are enabling tools applications biosensor systems, microarray technologies, fundamental biological studies and biointerface science. We have implemented method to create biomolecular patterns by using light control direct covalent immobilization onto benzophenone-modified glass substrates. generated substrates presenting up three different patterned sequence, demonstrate photopatterning on...
Affinity capture (AC) combined with mass spectrometry (MS)-based proteomics is highly utilized throughout the drug discovery pipeline to determine small-molecule target selectivity and engagement. However, tedious sample preparation steps time-consuming MS acquisition process have limited its use in a high-throughput format. Here, we report an automated workflow employing biotinylated probes streptavidin magnetic beads for enrichment 96-well plate format, ending direct sampling from EvoSep...
Abstract Introduction: Telisotuzumab Vedotin (Teliso-V), a first-in-class c-Met-MMAE antibody-drug conjugate (ADC), achieved FDA breakthrough therapy designation in c-Met overexpressing (OE), 2nd Line+ EGFR wild-type, non-squamous, non-small cell lung cancer (NSCLC) patients. In addition, phase 1/1b trial, Teliso-V demonstrated 50% response combination with the inhibitor, osimertinib, mutant (EGFR-MT) NSCLC patients who had progressed on osimertinib. Here, we present mechanistic insights...
We describe a new method to accomplish multiplexed, absolute protein quantification in targeted fashion. The approach draws upon the recently developed neutron encoding (NeuCode) metabolic labeling strategy and parallel reaction monitoring (PRM). Since PRM scanning relies high-resolution tandem mass spectra for quantification, incorporation of multiple NeuCode labeled peptides permits high levels multiplexing that can be accessed from spectra. Here we demonstrate this cultured cells by viral...
Periostin (PN, gene name POSTN) is an extracellular matrix protein that up-regulated in bronchial epithelial cells and lung fibroblasts by TH-2 cytokines. Its paralog, TGF-β-induced (βig-h3, TGFBI), also expressed the myofibroblasts TGF-β. PN βig-h3 contain fasciclin 1 modules harbor putative recognition sequences for γ-glutamyl carboxylase are annotated UniProt as undergoing vitamin K-dependent γ-carboxylation of multiple glutamic acid residues. profoundly alters activities other proteins...
Aggregation of misfolded α-synuclein (α-syn) is a key characteristic feature Parkinson's disease (PD) and related synucleinopathies. The nature these aggregates their contribution to cellular dysfunction still not clearly elucidated. We employed mass spectrometry-based total phospho-proteomics characterize the underlying molecular biological changes due α-syn aggregation using M83 mouse primary neuronal model PD. identified gross in proteome that coincided with formation large Lewy body-like...
Model substrates presenting biochemical cues immobilized in a controlled and well-defined manner are of great interest for their applications biointerface studies that elucidate the molecular basis cell receptor-ligand interactions. Herein, we describe direct, photochemical method to generate surface-immobilized biomolecular gradients applied study selectin-mediated leukocyte rolling. The technique employs benzophenone-modified glass substrates, which upon exposure UV light (350-365 nm)...
Label-free quantification is a powerful tool for the measurement of protein abundances by mass spectrometric methods. To maximize quantifiable identifications, MS(1)-based methods must balance collection survey scans and fragmentation spectra while maintaining reproducible extracted ion chromatograms (XIC). Here we present method which increases depth proteome coverage over replicate data-dependent experiments without requirement additional instrument time or sample prefractionation....
HIV-1 spreads efficiently through direct cell-to-cell transmission at virological synapses (VSs) formed by interactions between envelope proteins (Env) on the surface of infected cells and CD4 receptors uninfected target cells. Env-CD4 bring cellular membranes into close proximity induce transport viral factors to VS for efficient virion assembly transmission. Using novel, cell-specific stable isotope labeling quantitative mass spectrometric proteomics, we identified extensive changes in...
Abstract Affinity capture (AC) combined with mass spectrometry (MS)-based proteomics is highly utilized throughout the drug discovery pipeline to determine small molecule target selectivity and engagement. However, tedious sample preparation steps time-consuming MS acquisition process has limited its use in high-throughput format. Here, we report an automated workflow employing biotinylated probes streptavidin magnetic beads for enrichment 96-well plate format, ending direct sampling from...
Mechanical signals, such as those which are evoked during maximal intensity contractions (MIC), can induce an increase in skeletal muscle size. It has been widely concluded that this process is driven by the activation of rapamycin‐sensitive / mTORC1‐dependent signaling; however, recent studies have revealed mTORC1‐independent signaling events might also be involved. Thus, effort to identify these events, we generated a comprehensive map MIC‐regulated, and phosphoproteomes. In total,...
Identifying major histocompatibility complex (MHC) class I immunopeptide antigens represents a key step in the development of immune-based targeted therapeutics and vaccines. However, complete characterization these by tandem mass spectrometry remains challenging due to their short sequence length, high degree hydrophobicity, and/or lack sufficiently basic amino acids. This study seeks address potential for 193 nm ultraviolet photodissociation (UVPD) improve analysis MHC immunopeptides...