A5064860620- Autophagy in Disease and Therapy
- Mitochondrial Function and Pathology
- Endoplasmic Reticulum Stress and Disease
- Chronic Kidney Disease and Diabetes
- Advanced Proteomics Techniques and Applications
- RNA Research and Splicing
- Neurotransmitter Receptor Influence on Behavior
- PI3K/AKT/mTOR signaling in cancer
- Influenza Virus Research Studies
- Renal cell carcinoma treatment
- Metabolomics and Mass Spectrometry Studies
- Glycosylation and Glycoproteins Research
- DNA Repair Mechanisms
- SARS-CoV-2 and COVID-19 Research
- Galectins and Cancer Biology
- Protein Tyrosine Phosphatases
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Calcium signaling and nucleotide metabolism
- Health Systems, Economic Evaluations, Quality of Life
- Genetic Associations and Epidemiology
- Family and Patient Care in Intensive Care Units
- Advanced Biosensing Techniques and Applications
- Fungal Biology and Applications
European Molecular Biology Laboratory
2021-2025
University of Freiburg
2015-2024
University of California San Francisco Medical Center
2017
California Pacific Medical Center
2009
Abstract Amino acids (aa) are not only building blocks for proteins, but also signalling molecules, with the mammalian target of rapamycin complex 1 (mTORC1) acting as a key mediator. However, little is known about whether aa, independently mTORC1, activate other kinases mTOR network. To delineate aa-stimulated network dynamics, we here combine computational–experimental approach text mining-enhanced quantitative proteomics. We report that AMP-activated protein kinase (AMPK),...
Mechanistic target of rapamycin complex 1 (MTORC1) and polo like kinase (PLK1) are major drivers cancer cell growth proliferation, inhibitors both protein kinases currently being investigated in clinical studies. To date, MTORC1's PLK1's functions mostly studied separately, reports on their mutual crosstalk scarce. Here, we identify PLK1 as a physical MTORC1 interactor human cells. inhibition enhances activity under nutrient sufficiency starved cells, directly phosphorylates the component...
Abstract The Mitochondrial Complex I Assembly (MCIA) complex is essential for the biogenesis of respiratory (CI), first enzyme in chain, which has been linked to Alzheimer’s disease (AD) pathogenesis. However, how MCIA facilitates CI assembly, and it with AD pathogenesis, poorly understood. Here we report structural basis formation between subunits ECSIT ACAD9. binding induces a major conformational change FAD-binding loop ACAD9, releasing FAD cofactor converting ACAD9 from fatty acid...
Summary Dishevelled (Dvl) proteins are essential transducers in Wnt signaling pathways, which have been implicated development, stem cell maintenance, and human diseases such as cancer. Several studies shown that Dvl form dynamic biomolecular condensates. However, how cellular signals states influence the formation of condensates remains poorly understood. Here, we analyzed cells with endogenous Dvl2 using image-based sorting combination phosphoproteomics identified protein enrichment for...
Epigenome, transcriptome, and proteome analyses of postmortem brains have revealed initial molecular insights into cocaine use disorder (CUD). However, the inter-relationship between these omics contribution individual cell types remains largely unknown. We present an in-depth analysis changes in ventral striatum CUD at multi-omics single-cell resolution. Integrative microRNA sequencing (microRNA-seq), RNA (RNA-seq), proteomics datasets 41 individuals single-nuclei RNA-seq a subset 16...
Abstract Wnt signaling controls cell proliferation, differentiation, and migration, with critical roles in diseases such as cancer. It was proposed that relies on the formation of dynamic biomolecular condensates, “signalosome” “destruction complex”, a potential to modify spatial temporal regulation outcomes. To investigate role phase separation signaling, we generated line endogenously tagged Dvl2, central scaffolding protein, using mEos3.2 fluorophore. Applying live-cell single-molecule...
Abstract Systematic mapping of protein-ligand interactions is essential for understanding biological processes and drug mechanisms. Peptide-centric local stability assay (PELSA) a powerful tool detecting these localizing potential binding sites. However, its original workflow limited in throughput, sample compatibility accessible protein targets. Here, we introduce high-throughput adaptation - HT-PELSA that increases processing efficiency 100-fold while maintaining high sensitivity...
The serine/threonine kinase mammalian target of rapamycin (mTOR) governs growth, metabolism, and aging in response to insulin amino acids (aa), is often activated metabolic disorders cancer. Much known about the regulatory signaling network that encompasses mTOR, but surprisingly few direct mTOR substrates have been established date. To tackle this gap our knowledge, we took advantage a combined quantitative phosphoproteomic interactomic strategy. We analyzed insulin- aa-responsive...
Multiprotein complexes control the behavior of cells, such as lymphocytes immune system. Methods to affinity purify protein and determine their interactome by mass spectrometry are thus widely used. One drawback these methods is presence false positives. In fact, elution interest (POI) done changing biochemical properties buffer, so that unspecifically bound proteins (the positives) may also elute. Here, we developed an optogenetics-derived light-controlled purification method based on...
B cell antigen receptor (BCR) signaling is initiated by protein kinases and limited counteracting phosphatases that currently are less well studied in their regulation of BCR signaling. Here, we used the line Ramos to identify quantify human components. Specifically, a tyrosine phosphatase profiling revealed high expression 1B (PTP1B) naïve cells. The loss PTP1B leads increased activation. Through substrate trapping combination with quantitative mass spectrometry, identified 22 putative...
Endothelial cells (ECs) are primed to respond various signaling cues. For example, TGF (transforming growth factor)-β has major effects on EC function and phenotype by driving ECs towards a more mesenchymal state (ie, triggering endothelial activation), dynamic process associated with cardiovascular diseases. Although transcriptional regulation triggered TGF-β in is well characterized, post-transcriptional regulatory mechanisms induced remain largely unknown.Using RNA interactome capture, we...
Oligo/polynucleotide-based gene targeting strategies provide new options for achieving sequence-specific modification of genomic DNA and have implications the development therapies transgenic animal models. One such strategy, small fragment homologous replacement (SFHR), was evaluated qualitatively quantitatively in human lymphoblasts that contain a single base substitution hypoxanthine-guanine phosphoribosyl transferase (HPRT1) gene. Because HPRT1 mutant cells are readily discernable from...
The spike protein is the main component of SARS-CoV-2 virion surface. receptor-binding motif mediates recognition human angiotensin-converting enzyme 2 receptor, a critical step in infection, and preferential target for spike-neutralizing antibodies. Posttranslational modifications have been shown to modulate viral infectivity host immune response, but these are still being explored. Here we studied asparagine deamidation protein, spontaneous event that leads appearance aspartic isoaspartic...
Summary Gene duplication generates paralogs undergoing diverse fates during evolution and serves as a potent catalyst of biological complexity. Paralogs frequently share redundant functions may also exhibit antagonistic activities by competing for common interaction partners. Here we show that the gene NRBP1 NRBP2 oppositely regulate LINE1 retrotransposition, via influencing integrity ribonucleoprotein complex. We demonstrate opposite roles are not results competitive mechanism, but rather...
<title>Abstract</title> The understanding of ubiquitin E3 ligase function hinges on thoroughly identifying their cellular targets, but the transient nature signaling complexes leading to ubiquitination poses a significant challenge for detailed mechanistic studies. TRIM2 and TRIM3 are paralogous mammalian ligases with particularly high expression in brain, where they contribute neuronal development homeostasis. Here, we tailored recently developed ubiquitin-specific proximity labelling tools...
Abstract Epigenome, transcriptome, and proteome analyses of postmortem brains have revealed initial molecular insights into cocaine use disorder (CUD). However, the inter-relationship between these –omics contribution individual cell types remain largely unknown. We present an in-depth analysis changes in ventral striatum CUD at multi-omics single-cell resolution. Integrative microRNA-seq, RNA-seq, proteomics datasets 41 individuals single-nuclei RNA-seq a subset 16 conserved deregulation...
Kidney fibrosis, characterized by excessive extracellular matrix deposition, is a progressive disease that, despite affecting 10% of the population, lacks specific treatments and suitable biomarkers. This study presents comprehensive, time-resolved multi-omics analysis kidney fibrosis using an in vitro model system based on human PDGFRβ+ mesenchymal cells aimed at unraveling mechanisms. Using transcriptomics, proteomics, phosphoproteomics, secretomics we quantified over 14,000 biomolecules...
ABSTRACT B cell antigen receptor (BCR) signaling is initiated by protein kinases and limited counteracting phosphatases that currently are less well studied in their regulation of BCR signaling. We here used the line Ramos to identify quantify human components. Specifically, a tyrosine phosphatase profiling revealed high expression 1B (PTP1B) naïve cells. The loss PTP1B leads increased activation. Through substrate trapping combination with quantitative mass spectrometry, we identified 22...
Abstract The spike is the main protein component of SARS-CoV-2 virion surface. receptor binding motif mediates recognition hACE2 receptor, a critical infection step, and preferential target for spike-neutralizing antibodies. Post-translational modifications can modulate viral infectivity immune response. We studied in search asparagine deamidation, spontaneous event that leads to appearance aspartic isoaspartic residues, affecting both backbone its charge. used computational prediction...
Barchas, Denise; Gross, Kendall; Garwood, Charlotte; Schell-Chaple, Hildy; Schwarz, Jennifer; Lipshutz, Angela; Gropper, Michael UCSF Critical Care Innovations Group
Gross, Kendall; Schwarz, Jennifer; Khanna, Raman; Schell-Chaple, Hildy; Gropper, Michael; Lipshutz, Angela; Aldrich, Matthew; UCSF Critical Care Innovations Group
ABSTRACT The mitochondrial Complex I assembly (MCIA) complex is an essential player in the biogenesis of respiratory (CI), multiprotein responsible for initiation oxidative phosphorylation (OXPHOS). It not well understood how MCIA facilitates CI. Here we report structural basis formation between subunits ECSIT and ACAD9. binding induces a major conformational change FAD-binding loop ACAD9, resulting efflux FAD cofactor redeployment ACAD9 from fatty acid β-oxidation (FAO) to CI assembly. We...