A5025441654- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Advanced Proteomics Techniques and Applications
- Mitochondrial Function and Pathology
- RNA modifications and cancer
- Ocular Diseases and Behçet’s Syndrome
- Diabetes and associated disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Cell Adhesion Molecules Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Cellular transport and secretion
- Ubiquitin and proteasome pathways
- Mass Spectrometry Techniques and Applications
- Neuroscience and Neuropharmacology Research
- T-cell and B-cell Immunology
- RNA Research and Splicing
- Photoreceptor and optogenetics research
- Metabolomics and Mass Spectrometry Studies
- Systemic Lupus Erythematosus Research
- Immunotherapy and Immune Responses
- Complement system in diseases
- Peptidase Inhibition and Analysis
- Galectins and Cancer Biology
- RNA regulation and disease
- Neurogenesis and neuroplasticity mechanisms
Helmholtz Zentrum München
2016-2025
Center for Environmental Health
2007-2025
German Center for Diabetes Research
2016-2025
Heinrich Heine University Düsseldorf
2016-2025
Deutsches Diabetes-Zentrum e.V.
2016-2025
Ludwig-Maximilians-Universität München
1988-2023
Center for Integrated Protein Science Munich
2010-2022
University of Zurich
2022
München Klinik
2021
Bavarian Polymer Institute
2018
Ferroptosis is an iron-dependent form of regulated cell death linking iron, lipid, and glutathione levels to degenerative processes tumor suppression. By performing a genome-wide activation screen, we identified cohort genes antagonizing ferroptotic death, including GTP cyclohydrolase-1 (GCH1) its metabolic derivatives tetrahydrobiopterin/dihydrobiopterin (BH4/BH2). Synthesis BH4/BH2 by GCH1-expressing cells caused lipid remodeling, suppressing ferroptosis selectively preventing depletion...
Abstract Survival of plasma cells is regulated by B-cell maturation antigen (BCMA), a membrane-bound receptor activated its agonist ligands BAFF and APRIL. Here we report that γ-secretase directly cleaves BCMA, without prior truncation another protease. This direct shedding facilitated the short length BCMA’s extracellular domain. In vitro , reduces BCMA-mediated NF-κB activation. addition, releases soluble BCMA (sBCMA) acts as decoy neutralizing vivo inhibition enhances surface expression...
The plasma proteome is the ultimate target for biomarker discovery. It stores an endless amount of information on pathophysiological status a living organism, which is, however, still difficult to comprehensively access. high complexity can be addressed by either system-wide and unbiased tool such as mass spectrometry (LC-MS/MS) or highly sensitive targeted immunoassay proximity extension assay (PEA). To address relevant differences important shared characteristics, we tested performance...
Adipocyte-derived extracellular vesicles (AdEVs) are membranous nanoparticles that convey communication from adipose tissue to other organs. Here, delineate their role as messengers with glucoregulatory nature, we paired fluorescence AdEV-tracing and SILAC-labeling (phospho)proteomics, revealed AdEVs transfer functional insulinotropic protein cargo into pancreatic β-cells. Upon transfer, AdEV proteins were subjects for phosphorylation, augmented GPCR/cAMP/PKA signaling by increasing total...
Abstract DNA and histone modifications combine into characteristic patterns that demarcate functional regions of the genome 1,2 . While many ‘readers’ individual have been described 3–5 , how chromatin states comprising composite modification signatures, variants internucleosomal linker are interpreted is a major open question. Here we use multidimensional proteomics strategy to systematically examine interaction around 2,000 nuclear proteins with over 80 modified dinucleosomes representing...
Autoimmune uveitis is a blinding disease presenting with autoantibodies against eye-specific proteins as well autoagressive T cells invading and attacking the immune-privileged target tissue retina. The molecular events enabling to invade attack have remained elusive. Changes in membrane protein expression patterns between diseased healthy stages are especially interesting because initiating of will most likely occur at membranes. Since progression accompanied break-down blood-retinal...
To date, the proteomic profiling of Müller cells, dominant macroglia retina, has been hampered because absence suitable enrichment methods. We established a novel protocol to isolate native, intact cells from adult murine retinae at excellent purity which retain in situ morphology and are well suited for analyses. Two different strategies sample preparation - an StageTips (iST) subcellular fractionation approach including cell surface protein were used quantitative liquid chromatography-mass...
Purpose.: SNPs in chromosomal region 10q26 harboring PLEKHA1, ARMS2, and Htra1 showed the strongest association with age-related macular degeneration. Recent evidence suggests that patients homozygous for risk allele, lack of synthesis poorly characterized ARMS2 is causative this disorder. The present study was undertaken to gain an understanding genuine (patho)physiological role protein. Methods.: ARMS2-interacting proteins were identified by using a yeast two-hybrid system validated...
Abstract Regional lymph node metastasis negatively affects prognosis in colon cancer patients. The molecular processes leading to regional are only partially understood and proteomic markers for still scarce. Therefore, a tissue‐based approach was undertaken identifying proteins associated with metastasis. Two complementary methods have been employed. MALDI imaging used small (≤25 kDa) situ label‐free quantitative proteomics larger proteins. A tissue cohort comprising primary tumours without...
Astrocytes react to brain injury in a heterogeneous manner with only subset resuming proliferation and acquiring stem cell properties vitro. In order identify novel regulators of this subset, we performed genomewide expression analysis reactive astrocytes isolated 5 days after stab wound from the gray matter adult mouse cerebral cortex. The pattern was compared intact cortex neural cells (NSCs) subependymal zone (SEZ). These comparisons revealed set genes expressed at higher levels both...
To better understand the involvement of retinal Müller glial (RMG) cells in diseases, we phenotyped primary porcine RMGs dependence cultivation time using different quantitative proteomic strategies. A well‐established LC‐MS/MS‐based quantification method was employed: stable isotope labeling by amino acids cell culture (SILAC) and directly compared to label‐free (LF) quantifications, based on total peak intensities two programs (MaxQuant Progenesis LC‐MS). The overall numbers detected...
When nanoparticles (NP) enter the body they come into contact with fluids containing proteins which can adsorb to their surface. These may influence NP interactions biological vicinity, eventually determining fate inside body.
Article9 April 2018Open Access Transparent process Cross-talk between monocyte invasion and astrocyte proliferation regulates scarring in brain injury Jesica Frik Physiological Genomics, Biomedical Center, Ludwig-Maximilians-University Munich, Germany Institute for Stem Cell Research, Helmholtz Center Instituto de Biotecnología y Biología Molecular, UNLP-CONICET, La Plata, Argentina Search more papers by this author Juliane Merl-Pham Research Unit Protein Science, Nikolaus Plesnila Stroke...
RNA-binding proteins (RBPs) and long non-coding RNAs (lncRNAs) are key regulators of gene expression, but their joint functions in coordinating cell fate decisions poorly understood. Here we show that the expression activity RBP TDP-43 isoform lncRNA Neat1, scaffold nuclear compartment "paraspeckles," reciprocal pluripotent differentiated cells because cross-regulation. In cells, represses formation paraspeckles by enhancing polyadenylated short Neat1. also promotes pluripotency regulating...
Genome-wide association studies (GWAS) identified the MEIS1 locus for Restless Legs Syndrome (RLS), but causal single nucleotide polymorphisms (SNPs) and their functional relevance remain unknown. This contains a large number of highly conserved noncoding regions (HCNRs) potentially functioning as cis -regulatory modules. We analyzed these HCNRs allele-dependent enhancer activity in zebrafish mice found that risk allele lead SNP rs12469063 reduces Meis1 expression domain murine embryonic...
Abstract Ragweed pollen is the main cause of allergenic diseases in Northern America, and weed has become a spreading neophyte Europe. Climate change air pollution are speculated to affect potential pollen. The objective this study was investigate effects NO 2 , major pollutant, under controlled conditions, on allergenicity ragweed exposed different levels throughout entire growing season, its further analysed. Spectroscopic analysis showed increased outer cell wall polymers decreased...
BAFF and a proliferation-inducing ligand (APRIL), which control B cell homeostasis, are therapeutic targets in autoimmune diseases. TACI-Fc (atacicept), soluble fusion protein containing the extracellular domain of BAFF-APRIL receptor TACI, was applied clinical trials. However, disease activity multiple sclerosis unexpectedly increased, whereas systemic lupus erythematosus, atacicept beneficial. In this study, we show that an endogenous TACI (sTACI) exists vivo. proteolysis involved shedding...
Complement dysregulation is a feature of many retinal diseases, yet mechanistic understanding at the cellular level limited. Given this knowledge gap about which cells express complement, we performed single-cell RNA sequencing on ∼92,000 mouse and validated our results in five major purified cell types. We found evidence for distributed cell-type-specific complement expression across 11 Notably, Müller are contributor activators c1s, c3, c4, cfb. Retinal pigment epithelium (RPE) mainly...
Internal organs heal injuries with new connective tissue, but the cellular and molecular events of this process remain obscure. By tagging extracellular matrix around mesothelium lining in mouse peritoneum, liver cecum, here we show that preexisting was transferred across into wounds various injury models. Using proteomics, genetic lineage-tracing selective juxtaposed organs, found tissue origin for likely dictated scarring or regeneration healing tissue. Single-cell RNA sequencing chemical...
Ferroptosis is an iron-dependent form of cell death driven by biochemical processes that promote oxidation within the lipid compartment. Calcium (Ca2+) a signaling molecule in diverse cellular such as migration, neurotransmission, and death. Here, we uncover crucial link between ferroptosis Ca2+ through identification novel tetraspanin MS4A15. MS4A15 localizes to endoplasmic reticulum, where it blocks depleting luminal stores reprogramming membrane phospholipids ferroptosis-resistant...