A5031483671- Advanced Proteomics Techniques and Applications
- Lysosomal Storage Disorders Research
- Acute Myeloid Leukemia Research
- Mass Spectrometry Techniques and Applications
- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Epigenetics and DNA Methylation
- Acute Lymphoblastic Leukemia research
- Biosimilars and Bioanalytical Methods
- Muscle Physiology and Disorders
- TGF-β signaling in diseases
- Trypanosoma species research and implications
- Monoclonal and Polyclonal Antibodies Research
- Drug Transport and Resistance Mechanisms
- PARP inhibition in cancer therapy
- Glycogen Storage Diseases and Myoclonus
- Immune Response and Inflammation
- Ubiquitin and proteasome pathways
- Advanced biosensing and bioanalysis techniques
- Virus-based gene therapy research
- NF-κB Signaling Pathways
- T-cell and B-cell Immunology
- Cell death mechanisms and regulation
- Analytical Chemistry and Chromatography
- Drug-Induced Hepatotoxicity and Protection
University of Duisburg-Essen
2025
University of Trieste
2024
The University of Texas MD Anderson Cancer Center
2011-2021
Takeda (United States)
2015-2019
Tesaro (United States)
2018-2019
University of California, San Francisco
1997-2001
Engagement of the immunoinhibitory receptor, programmed death‐1 (PD‐1) attenuates T‐cell receptor (TCR)‐mediated activation IL‐2 production and proliferation. Here, we demonstrate that PD‐1 modulation function involves inhibition TCR‐mediated phosphorylation ZAP70 association with CD3ζ. In addition, signaling PKCθ loop in a cognate TCR signal. has been shown to be required for production. A phosphorylated peptide, corresponding C‐terminal immunoreceptor tyrosine‐switch motif (ITSM), acts as...
Myostatin, also known as growth and differentiation factor 8, is a member of the transforming β superfamily that negatively regulates skeletal muscle mass (1McPherron A.C. Lawler A.M. Lee S.J. Nature. 1997; 387: 83-90Google Scholar). Recent experiments have shown myostatin activity detected in serum by reporter gene assay only after activation acid, suggesting native circulates latent complex (2Zimmers T.A. Davies M.V. Koniaris L.G. Haynes P. Esquela A.F. Tomkinson K.N. McPherron Wolfman...
Liver toxicity following an overdose of acetaminophen is frequently considered a model for drug-induced hepatotoxicity. Extensive studies over many years have established that such well correlated with liver protein arylation by metabolites. Identification targets covalent modifications challenging but necessary step in understanding how binding could lead to toxicity. Previous approaches suffered from technical limitations, and thus the last 10 heroic efforts were required determine...
Myostatin, a member of the TGFbeta superfamily, is potent and specific negative regulator skeletal muscle mass. In serum, myostatin circulates as part latent complex containing propeptide and/or follistatin-related gene (FLRG). Here, we report identification an additional protein associated with endogenous in normal mouse human discovered by affinity purification mass spectrometry. This protein, which have named growth differentiation factor-associated serum protein-1 (GASP-1), contains...
Synergistic molecular vulnerabilities enhancing hypomethylating agents in myeloid malignancies have remained elusive. RNA-interference drug modifier screens identified antiapoptotic BCL-2 family members as potent 5-Azacytidine-sensitizing targets. In further dissecting BCL-XL, and MCL-1 contribution to 5-Azacytidine activity, siRNA silencing of BCL-XL MCL-1, but not BCL-2, exhibited variable synergy with vitro. The BCL-w inhibitor ABT-737 sensitized most cell lines more potently compared the...
Allergic asthma is characterized by persistent airway inflammation and remodeling. Bronchoalveolar lavage conducted with fiberoptic bronchoscopy has been widely used for investigating the pathogenesis of other lung disorders. Identification proteins in bronchoalveolar fluid (BALF) their expression changes at different stages could provide further insights into complex molecular mechanisms involved this disease. In report, we describe first comprehensive differential proteomic analysis BALF...
Abstract Objective To identify potential molecular mediators and biomarkers for osteoarthritis (OA), through comparative proteomic analysis of articular cartilage tissue obtained from normal donors without OA (n = 7) patients with 7). Methods The analyses comprised extraction soluble proteins cartilage, separation the protein mixtures by sodium dodecyl sulfate–polyacrylamide gel electrophoresis followed in‐gel digestion, subsequent nano‐liquid chromatography–tandem mass spectrometry in...
This was an open-label, phase 1/2 dose-escalation, safety trial of intrathecal recombinant human heparan-N-sulfatase (rhHNS) administered via drug delivery device (IDDD) for treating mucopolysaccharidosis IIIA (NCT01155778).Twelve patients received 10, 45, or 90mg rhHNS IDDD once monthly a total 6 doses. Primary endpoints included adverse events (AEs) and anti-rhHNS antibodies. Secondary standardized neurocognitive assessments, cortical gray matter volume, pharmacokinetic/pharmacodynamic...
Myostatin is a secreted TGF-beta family member that controls skeletal muscle growth. Humans, cattle, and dogs carrying natural loss-of-function mutations in the myostatin gene knockout mice exhibit significant increases mass. Treatment of adult with antimyostatin antibodies also resulted mass increases. However, myostatin-knockout were treated soluble form activin type II receptor (ActRII) B increased their by an additional 15-25%, indicating there at least one ligand, addition to myostatin,...
As part of our effort to identify putative protein targets for the development male contraceptives, we performed an in-depth proteomic analysis human sperm by liquid chromatography and tandem mass spectrometry. Motile were collected from a single fertile individual fractionated into detergent-soluble detergent-insoluble fractions. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis separation these fractions, followed manual cutting gel, yielded 35 sections each fraction include...
The 2016 10th Workshop on Recent Issues in Bioanalysis (10th WRIB) took place Orlando, Florida with participation of close to 700 professionals from pharmaceutical/biopharmaceutical companies, biotechnology contract research organizations, and regulatory agencies worldwide. WRIB was once again a weeklong event - A Full Immersion Week for PK, Biomarkers Immunogenicity. As usual, it is specifically designed facilitate sharing, reviewing, discussing agreeing approaches address the most current...
Mass spectrometry (MS) has emerged as a sensitive, versatile, and rapid method for protein identification, following the advent of electrospray ionization mass (ESI-MS) matrix-assisted laser desorption/ionization (MALDI-MS). The advantages MALDI-MS over ESI-MS include its relatively high tolerance to contamination from biological matrices, sensitivity, relative ease interpreting spectra mixtures, formation singly protonated molecular ions tandem analysis. Peptide fingerprint mapping partial...
Quantitative mass spectrometry using stable isotope-labeled tagging reagents such as isotope-coded affinity tags has emerged a powerful tool for identification and relative quantitation of proteins in current proteomic studies. Here we describe an integrated approach both automated two-dimensional liquid chromatography/ (2D-LC/MS) novel class chemically modified resins, termed acid-labile extractants (ALICE), quantitative spectrometric analysis protein mixtures. ALICE contains thiol-reactive...
Gaucher disease (GD), an autosomal recessive lipid storage disorder, arises from mutations in the GBA1 (β-glucocerebrosidase) gene, resulting glucosylceramide accumulation tissue macrophages. Lyso-Gb1 (glucosylsphingosine, lyso-GL1), a downstream metabolic product of glucosylceramide, has been identified as promising biomarker for diagnosis and monitoring patients with GD. This retrospective, exploratory analysis data phase 3 clinical trials velaglucerase alfa type 1 GD evaluated potential...