A5069146576- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Click Chemistry and Applications
- Protease and Inhibitor Mechanisms
- Glycosylation and Glycoproteins Research
- Protein Degradation and Inhibitors
- Cytokine Signaling Pathways and Interactions
- Machine Learning in Bioinformatics
- Monoclonal and Polyclonal Antibodies Research
- Genomics and Phylogenetic Studies
- Lysosomal Storage Disorders Research
- S100 Proteins and Annexins
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Folate and B Vitamins Research
- Bacterial Genetics and Biotechnology
- Histone Deacetylase Inhibitors Research
- RNA regulation and disease
- Wnt/β-catenin signaling in development and cancer
- Nasolacrimal Duct Obstruction Treatments
- Ophthalmology and Eye Disorders
- Chemokine receptors and signaling
- Ocular Disorders and Treatments
University of Toronto
2023-2025
Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital
2024
Scripps Research Institute
2020-2023
Technical University of Munich
2014-2018
Center for Integrated Protein Science Munich
2015-2018
Klinikum rechts der Isar
2012-2015
Max Planck Institute of Biochemistry
2010
Max Planck Society
2010
Shanghai Tenth People's Hospital
2009
Due to its ability inhibit prometastatic matrix metalloproteinases, tissue inhibitor of metalloproteinases (TIMP)-1 has been thought suppress tumor metastasis. However, elevated systemic levels TIMP-1 correlate with poor prognosis in cancer patients, suggesting a metastasis-stimulating role TIMP-1. In colorectal as well plasma were correlated synchronous liver metastasis or distant metastasis-associated disease relapse. mice, high increased the susceptibility towards by triggering formation...
Abstract The concept of proteasome inhibition ranks among the latest achievements in treatment blood cancer and represents a promising strategy for modulating autoimmune diseases. In this study, we describe peptidic sulfonyl fluoride inhibitors that selectively block catalytic β5 subunit immunoproteasome by inducing only marginal cytotoxic effects. Structural mass spectrometric analyses revealed novel reaction mechanism involving polarity inversion irreversible crosslinking proteasomal...
Abstract The ubiquitin–proteasome system (UPS) has been successfully targeted by both academia and the pharmaceutical industry for oncological immunological applications. Typical proteasome inhibitors are based on a peptidic backbone endowed with an electrophilic C‐terminus which they react active proteolytic sites. Although peptide moiety attracted much attention in terms of subunit selectivity, target specificity biological stability compounds largely determined reactive warheads. In this...
Development of antimalarial compounds into clinical candidates remains costly and arduous without detailed knowledge the target. As resistance increases treatment options at various stages disease are limited, it is critical to identify multistage drug targets that readily interrogated in biochemical assays. Whole-genome sequencing 18 parasite clones evolved using thienopyrimidine with submicromolar, rapid-killing, pan-life cycle antiparasitic activity showed all had acquired mutations P....
Biology has been transformed by the rapid development of computing and concurrent rise data-rich approaches such as -omics or high-resolution imaging. However, there is a persistent computational skills gap in biomedical research workforce. Inherent limitations classroom teaching institutional core support highlight need for accessible ways researchers to explore developments biology. An analysis Scripps Research Genomics Core revealed an increasingly diverse set experiments: share...
The homeostasis of neutrophil granulocytes can affect the outcome several inflammation-associated diseases including cancer. regulation this is still not completely understood. We previously found that elevated systemic levels tissue inhibitor metalloproteinases-1 (TIMP-1) induce an increase neutrophils in liver, which turn strongly promotes liver metastasis. Here, we report increasing TIMP-1 were sufficient to neutrophilia mice. This was attributed prolonged survival or direct mobilization...
Abstract During mRNA translation, tRNAs are charged by aminoacyl-tRNA synthetases and subsequently used ribosomes. A multi-enzyme synthetase complex (MSC) has been proposed to increase protein synthesis efficiency passing An alternative function is that the MSC repurposes specific released from upon cues for functions independent of translation. To explore this, we generated mammalian cells in which arginyl-tRNA and/or glutaminyl-tRNA were absent MSC. Protein synthesis, under a variety...
Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes in translation by linking amino acids onto their cognate tRNAs during protein synthesis. During evolution, aaRSs develop numerous non-canonical functions that expand the roles of eukaryotic organisms. Although have been implicated viral infection, function infections with coronaviruses (CoVs) remains unclear. Here, we analyzed data from transcriptomic and proteomic database on human cytoplasmic (cyto) mitochondrial (mt) across three...
In contrast to expectations in the past that tumor starvation or unselective inhibition of proteolytic activity would cure cancer, there is accumulating evidence microenvironmental stress, such as hypoxia broad-spectrum metalloproteinases can promote metastasis. fact, malignant cells, due their genetic and epigenetic instability, are predisposed react stress by adaptation and, if persists, escape formation Recent recognition concepts dynamic evolution well population systems biology...
The tetraspanin CD63 is implicated in pro-metastatic signaling pathways but, so far, it unclear, how levels affect the tumor cell phenotype. Here, we investigated effect of modulation different metastatic lines. In vitro, knock down induced a more epithelial-like phenotype concomitant with increased E-cadherin expression, downregulation its repressors Slug and Zeb1, decreased N-cadherin. addition, β-catenin protein was markedly reduced, negatively affecting expression target genes MMP-2...
Abstract Clinically applied proteasome inhibitors induce cell death by concomitant blockage of constitutive and immunoproteasomes. In contrast, selective immunoproteasome inhibition is less cytotoxic has the potential to modulate chronic inflammation autoimmune diseases. this study, we rationally designed decarboxylated peptides that covalently target a non‐catalytic cysteine subunit β5i with α‐chloroacetamide‐containing sidechains. The enhanced isoform specificity decreased effects compound...
Protein activity is often regulated by altering the oligomerization state. One mechanism of multimerization involves domain swapping, wherein proteins exchange parts their structures and thereby form long-lived dimers or multimers. Domain swapping has been specifically observed in amyloidogenic proteins, for example cystatin superfamily cysteine protease inhibitors. Cystatins are twin-headed inhibitors, simultaneously targeting lysosomal cathepsins legumain, with important roles cancer...
Aminoacyl-tRNA synthetases (aaRSs) are key enzymes in the mRNA translation machinery, yet they possess numerous non-canonical functions developed during evolution of complex organisms. The aaRSs and aaRS-interacting multi-functional proteins (AIMPs) continually being implicated tumorigenesis, but these connections often limited scope, focusing on specific distinct cancer subtypes. Here, we analyze publicly available genomic transcriptomic data human cytoplasmic mitochondrial across many...
Glycans are emerging as important regulators of T cell function but remain poorly characterized across the functionally distinct populations that exist
The aminoacyl-tRNA synthetases (aaRS) are a large group of enzymes that implement the genetic code in all known biological systems. They attach amino acids to their cognate tRNAs, moonlight various translational and non-translational activities beyond aminoacylation, linked many disorders. aaRS have subtle ontology characterized by structural functional idiosyncrasies vary from organism organism, protein protein. Across tree life, 22 coded handled 16 evolutionary families Class I 21 II aaRS....
Tellurophene-bearing small molecules have emerged as valuable tools for localizing cellular activities
Abstract Das Ubiquitin‐Proteasom‐System (UPS) wurde in akademischer wie pharmazeutischer Forschung erfolgreich für onkologische und immunologische Anwendungen adressiert. Typische Proteasominhibitoren basieren auf einem peptidischen Rückgrat, das mit elektrophilen C‐Terminus zur Bindung an die aktiven proteolytischen Zentren gekuppelt ist. Obwohl der peptidische Anteil viel Interesse bezüglich Untereinheitenselektivität hervorgerufen hat, wird Wirkspezifität biologische Stabilität Substanzen...
Abstract Translational readthrough of UGA stop codons by selenocysteine-specific tRNA (tRNASec) enables the synthesis selenoproteins. Seryl-tRNA synthetase (SerRS) charges tRNASec with serine, which is modified into selenocysteine and delivered to ribosome a designated elongation factor (eEFSec in eukaryotes). Here we found that components human incorporation machinery (SerRS, tRNASec, eEFSec) also increased translational non-selenocysteine genes, including VEGFA, create C-terminally...
Abstract Das Konzept der Proteasom‐Inhibition zählt zu den jüngsten Errungenschaften Blutkrebstherapie und stellt eine vielversprechende Strategie zur Regulierung von Autoimmunerkrankungen dar. Diese Arbeit beschreibt die selektive Hemmung katalytischen β5‐Untereinheit des Immunoproteasoms durch peptidische Sulfonylfluoride, nur geringen zytotoxischen Effekt haben. Strukturelle massenspektrometrische Analysen offenbarten einen neuartigen Inhibitionsmechanismus, einer Umpolung irreversiblen...
Abstract Selective inhibition of the immunoproteasome is a promising approach towards development immunomodulatory drugs. Recently, class substituted thiazole compounds that combine nonpeptidic scaffold with absence an electrophile was reported in patent. Here, we investigated mode action lead compound by using sophisticated chimeric yeast model human for structural studies. The inhibitor adopts unique orientation perpendicular to β5i substrate‐binding channel. Distinct interactions between...