A5077830669- Methane Hydrates and Related Phenomena
- Ionosphere and magnetosphere dynamics
- Geophysics and Gravity Measurements
- Seismic Waves and Analysis
- Earthquake Detection and Analysis
- Immune cells in cancer
- Phagocytosis and Immune Regulation
- Immunotherapy and Immune Responses
- Astrophysics and Cosmic Phenomena
- Advanced Proteomics Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- Mass Spectrometry Techniques and Applications
- HER2/EGFR in Cancer Research
- Metabolomics and Mass Spectrometry Studies
- Biosimilars and Bioanalytical Methods
- RNA and protein synthesis mechanisms
- Protein purification and stability
- Advanced Biosensing Techniques and Applications
- Glycosylation and Glycoproteins Research
- Cell Adhesion Molecules Research
- Epigenetics and DNA Methylation
- PARP inhibition in cancer therapy
- Biochemical and Structural Characterization
- Pharmacogenetics and Drug Metabolism
- Analytical Chemistry and Chromatography
Pfizer (United States)
2024-2025
Seagen (United States)
2014-2024
Pacific Northwest National Laboratory
2012-2023
Novartis (Switzerland)
2022
UCB Pharma (United Kingdom)
2022
Eli Lilly (United States)
2022
Roche (Switzerland)
2022
Janssen (United States)
2022
Novartis Institutes for BioMedical Research
2022
Biogen (United States)
2022
Abstract Post-translational modifications (PTMs) of core histones work synergistically to fine tune chromatin structure and function, generating a so-called histone code that can be interpreted by variety interacting proteins. We report novel online two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) platform for high-throughput sensitive characterization PTMs at the intact protein level. The enables unambiguous identification 708 isoforms from single 2D LC-MS/MS...
Ritonavir is a human immunodeficiency virus (HIV) protease inhibitor and an of cytochrome P450 3A4, the major hepatic drug-metabolizing enzyme. Given potent inhibition CYP3A4 by ritonavir, subtherapeutic doses ritonavir are used to increase plasma concentrations other HIV drugs oxidized CYP3A4, thereby extending their clinical efficacy. However, mechanism remains unclear. To date, data suggests multiple types including mechanism-based inactivation metabolic-intermediate complex formation,...
Analysis of samples containing intact antibody-drug conjugates (ADC) using mass spectrometry provides a direct measurement the drug-load distribution. Once dosed, drug load distribution changes due to combination biological and chemical factors. Liquid chromatography-mass (LC-MS) methods measure in vivo have been established for ADCs native disulfide bonds (lysine-linked or cysteine-linked). However, because an IgG reduction step conjugation processes, LC-MS analyze cysteine-linked requires...
Post-translational modifications (PTMs) play an important role in various biological processes through changing protein structure and function. Some ultramodified proteins (like histones) have multiple PTMs forming PTM patterns that define the functionality of a protein. While bottom-up mass spectrometry (MS) has been successful identifying individual within short peptides, it is unable to identify spreading along entire coordinated fashion. In contrast, top-down MS analyzes intact reveals...
The 15th edition of the Workshop on Recent Issues in Bioanalysis (15th WRIB) was held 27 September to 1 October 2021. Even with a last-minute move from in-person virtual, an overwhelmingly high number nearly 900 professionals representing pharma and biotech companies, contract research organizations (CROs), multiple regulatory agencies still eagerly convened actively discuss most current topics interest bioanalysis. WRIB included 3 Main Workshops 7 Specialized that together spanned week...
The 17
A label-free quantitative variation of the recently developed data-independent shotgun proteomic method precursor acquisition independent from ion count (PAcIFIC) was used to identify novel proteins implicated in cancer progression and resistance. Specifically, this screen identified pro-metastatic protein anterior gradient 2 (AGR2) as significantly up-regulated tamoxifen-treated cells. Highlighting need for direct proteome profiling methods like PAcIFIC, neither data-dependent gas-phase...
Antibody-drug conjugates (ADCs) require multiple assays to characterize their PK. These can separately evaluate the ADC by quantifying antibody or conjugated drug and may give different answers due assay measurement differences, heterogeneous nature of ADCs potential biotransformations that occur in vivo.We present a new version antibody-conjugated for valine-citrulline-linked monomethylauristatin E (vcMMAE) ADCs. A stable isotope-labeled internal standard, protein affinity capture...
The 2019 13th Workshop on Recent Issues in Bioanalysis (WRIB) took place New Orleans, LA, USA April 1–5, with an attendance of over 1000 representatives from pharmaceutical/biopharmaceutical companies, biotechnology contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day, week-long event – full immersion week bioanalysis, biomarkers, immunogenicity gene therapy. As usual, it specifically designed to facilitate sharing, reviewing, discussing agreeing...
Inhibition of glycoprotein fucosylation, as monotherapy and in combination with immune checkpoint blockade, is a promising therapeutic strategy for treating broad range cancers. In this first-in-human, first-in-class, phase I study advanced solid tumors, SGN-2FF demonstrated dose-proportional pharmacokinetics, evidence pharmacodynamic target inhibition preliminary antitumor activity. was associated thromboembolic events that led to termination.We conducted SGN-2FF, potent small-molecule...
Bacterial adenosine diphosphate-ribosyltransferases (ADPRTs) are toxins that play a significant role in pathogenicity by inactivating host proteins through covalent addition of ADP-ribose. In this study we used ADP-ribosylated Kemptide (LRRASLG) as standard to examine the effectiveness three common tandem mass spectrometry fragmentation methods for assignment amino acid sequence and site modification. Fragmentation mechanisms investigated include low-energy collision-induced dissociation...
<p>Supplementary Figure 19. Protease activity of select syngeneic and xenograft tumor models was assessed using an activatable cell-penetrating peptide (ACPP)2 bearing the -IPVSLRSG- cleavage sequenced used in Coil-MMP-mIAP301 SGN-CD47M antibodies.</p>
<p>Supplementary Figure 12. Hemagglutination activity of hB6H12.3, SGN-CD47M, MMP-cleaved and an IgG1 isotype control on human red blood cells, as assessed by optical measurement spot size following incubation with increasing concentrations antibodies.</p>
<p>Supplementary Figure 6. hB6H12.3, bearing a human IgG1 Fc region elicits stronger phagocytosis of red blood cells by monocytes in vitro compared to IgG4 competitor antibodies HuF9-G4 and CC-90002.</p>
<p>Supplementary Figure 13. Assessment of the ability hB6H12.3, SGN-CD47M, MMP-cleaved SGN-CD47, and a IgG1 isotype control antibody to induce direct apoptosis THP1 cells, as assessed by flow cytometry Annexin V cell surface expression.</p>
<p>Supplementary Figure 2. Concentration-time profiles of 3H-labeled mIAP301 and Coil-MMP-mIAP301 were profiled in the plasma, liver, tumors BALB/c mice bearing A20 lymphoma once reached approximately 250 mm3 size.</p>
<p>Supplementary Figure 15. Anti-CD47 antibody mediated FcgRIIa-H131 signaling, assessed using FcγRIIa Jurkat NFAT reporter cells incubated with CD47-expressing WIL2-S target and increasing concentrations of anti-CD47 antibodies or isotype control.</p>
<p>Supplementary Figure 17. F4/80 staining of select xenograft tumor models used in the study.</p>