A5009747953- Neuroinflammation and Neurodegeneration Mechanisms
- Anesthesia and Neurotoxicity Research
- Glioma Diagnosis and Treatment
- Genomics and Chromatin Dynamics
- Histone Deacetylase Inhibitors Research
- Epigenetics and DNA Methylation
- Chromosomal and Genetic Variations
- Lysosomal Storage Disorders Research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Neurological Disease Mechanisms and Treatments
- Extracellular vesicles in disease
- MicroRNA in disease regulation
- Peroxisome Proliferator-Activated Receptors
- Nuclear Receptors and Signaling
- Alzheimer's disease research and treatments
- Inflammasome and immune disorders
- IL-33, ST2, and ILC Pathways
- Immune cells in cancer
- Peptidase Inhibition and Analysis
- Computational Drug Discovery Methods
- Developmental Biology and Gene Regulation
- Atherosclerosis and Cardiovascular Diseases
- Studies on Chitinases and Chitosanases
- Sphingolipid Metabolism and Signaling
- Genetic Associations and Epidemiology
Ludwig-Maximilians-Universität München
2005-2025
German Center for Neurodegenerative Diseases
2024
LMU Klinikum
2017-2020
Center for Integrated Protein Science Munich
2010-2016
Heidelberg University
2002-2005
University of California, Santa Cruz
2000
Currently, there are no blood-based biomarkers with clinical utility for acute ischemic stroke (IS). MicroRNAs show promise as disease markers because of their cell type-specific expression patterns and stability in peripheral blood.To identify circulating microRNAs associated IS, determine temporal course up to 90 days post-stroke, explore an early diagnostic marker.We used RNA sequencing study changes a discovery sample 20 patients IS matched healthy control subjects. We further applied...
Common genetic variants in a conserved cis-regulatory element (CRE) at histone deacetylase (HDAC)9 are major risk factor for cardiovascular disease, including stroke and coronary artery disease. Given the consistency of this association its proinflammatory properties, we examined mechanisms whereby HDAC9 regulates vascular inflammation. bound mediated deacetylation NLRP3 NACHT LRR domains leading to inflammasome activation lytic cell death. Targeted deletion critical CRE mice increased Hdac9...
Polycomb group response elements (PREs) mediate the mitotic inheritance of gene expression programs and thus maintain determined cell fates. By default, PREs silence associated genes via targeting (PcG) complexes. Upon an activating signal, however, recruit counteracting trithorax (trxG) proteins, which in turn target a transcriptionally active state. Using transgenic reporter system, we show that switch from silenced to activated state PRE requires noncoding transcription. Continuous...
Article18 January 2016Open Access Transparent process Life span extension by targeting a link between metabolism and histone acetylation in Drosophila Shahaf Peleg Department of Physiological Chemistry, Biomedical Center for Integrated Protein Science Munich, Ludwig-Maximilians University, Planegg-Martinsried, Germany Molecular Biology, Search more papers this author Christian Feller Ignasi Forne Analysis Unit, Center, Evelyn Schiller Institute Experimental Genetics, Helmholtz Zentrum German...
Microglial dysfunction is a key pathological feature of Alzheimer's disease (AD), but little known about proteome-wide changes in microglia during the course AD and their functional consequences. Here, we performed an in-depth time-resolved proteomic characterization two mouse models amyloid β (Aβ) pathology, overexpression APPPS1 knock-in APP-NL-G-F (APP-KI) model. We identified large panel Aβ Response Proteins (MARPs) that reflect heterogeneity microglial alterations early, middle advanced...
Arterial inflammation manifested as atherosclerosis is the leading cause of mortality worldwide. Genome-wide association studies have identified a prominent role HDAC (histone deacetylase)-9 in and its clinical complications including stroke myocardial infarction. To determine mechanisms linking HDAC9 to these vascular pathologies explore therapeutic potential for atheroprotection. We studied effects Hdac9 on features plaque vulnerability using bone marrow reconstitution experiments...
The proteins of the trithorax and Polycomb groups maintain differential expression pattern homeotic genes established by early embryonic patterning system during development. These generate stable heritable chromatin structures acting via particular chromosomal memory elements. We a transgenic assay showing that group response elements bxd Mcp confer epigenetic inheritance throughout With previously published data for Fab7 cellular module, we confirmed function In Drosophila melanogaster,...
The 100 copies of tandemly arrayed Drosophila linker (H1) and core (H2A/B H3/H4) histone gene cluster are coordinately regulated during the cell cycle. However, molecular mechanisms that must allow differential transcription versus histones prevalent development remain elusive. Here, we used fluorescence imaging, biochemistry, genetics to show TBP (TATA-box-binding protein)-related factor 2 (TRF2) selectively regulates TATA-less Histone H1 promoter, while TBP/TFIID targets transcription....
The MOF (males absent on the first)-containing NSL (non-specific lethal) complex binds to a subset of active promoters in Drosophila melanogaster and is thought contribute proper gene expression. determinants that target specific circumstances which engages regulating transcription are currently unknown. Here, we show primarily targets particular housekeeping genes, at it colocalizes with chromatin remodeler NURF (nucleosome remodeling factor) histone methyltransferase Trithorax. However,...
Background and Purpose— Genome-wide association studies have identified the HDAC9 (histone deacetylase 9) gene region as a major risk locus for atherosclerotic stroke coronary artery disease in humans. Previous results suggest role of altered expression levels underlying mechanism. rs2107595, lead single nucleotide polymorphism resides noncoding DNA colocalizes with histone modification marks suggestive enhancer elements. Methods— To determine mechanisms by which genetic variation at...
Abstract Genome-wide association studies (GWAS) have identified over two hundred chromosomal loci that modulate risk of coronary artery disease (CAD). The genes affected by variants at these are largely unknown and an untapped resource to improve our understanding CAD pathophysiology identify potential therapeutic targets. Here, we prioritized 68 as the most likely causal genome-wide significant GWAS examined their regulatory roles in 286 metabolic vascular tissue gene-protein sub-networks...
Niemann–Pick type C (NPC) disease is a rare progressive lysosomal lipid storage disorder that manifests with heterogeneous spectrum of clinical syndromes, including visceral, neurological and psychiatric symptoms. This monogenetic autosomal recessive largely caused by mutations in the NPC1 gene, which controls intracellular homeostasis. Vesicle-mediated endo-lysosomal trafficking non-vesicular exchange via inter-organelle membrane contact sites are both regulated protein. Loss function...
Atherosclerosis leads to vascular lesions that involve major rearrangements of the proteome, especially extracellular matrix (ECM). Using single aortas from ApoE knock out mice, we quantified formation plaques by single-run, high-resolution mass spectrometry (MS)-based proteomics. To probe localization on a proteome-wide scale employed quantitative detergent solubility profiling. This compartment- and time-resolved resource atherogenesis comprised 5117 proteins, 182 which changed their...
Loss-of-function mutations in CLN3 cause juvenile Batten disease, featuring neurodegeneration and early-stage neuroinflammation. How loss of function leads to early neuroinflammation is not yet understood. Here, we have comprehensively studied microglia from Cln3∆ex7/8 mice, a genetically accurate disease model. Loss lysosomal storage material accumulation abnormal morphology subcellular organelles. Moreover, pathological proteomic signatures are indicative defects lipid metabolism....
Recently, our group has discovered a family suffering from premature coronary artery disease (CAD) and myocardial infarction (MI). Whole-exome sequencing of three affected members revealed that these shared mutation in the PDE5A gene encoding phosphodiesterase 5A protein. Mutations proteins involved cGMP-signalling have already been shown to play an important role CAD/MI [1]. Here, we aimed characterize effect this at molecular level. PDE5A encodes distinct isoforms, PDE5A1, PDE5A2,...
Current therapy strategies still provide only limited success in the treatment of glioblastoma, most frequent primary brain tumor adults. In addition to characterization microenvironment, global changes patients with glioblastoma have been described. However, impact and molecular signature neuroinflammation distant site not yet thoroughly elucidated.
<p>Contralateral hemispheres of SB28 glioblastoma mice indicate signatures disease-associated myeloid cells and immunosuppression. <b>A,</b> Volcano plot highlights genes with significant upregulation downregulation in the contralateral hemisphere (red blue, respectively) compared to sham. <b>B,</b> qPCR reveals higher expression related an inflammatory cell state contrast <b>C,</b> Illustration 50 pathways highest elevation immune (informed by IPA)....
<p>Characteristics of the cohort.</p>
<p>Elevated TSPO-PET signals in the non-lesional hemisphere of patients with glioblastoma. <b>A,</b> Patient selection process. Patients receiving imaging at initial diagnosis glioma were allocated. unilateral manifestation glioblastoma (WHO IV; <i>n</i> = 41) or isocitrate dehydrogenase mutant astrocytoma WHO grade 2 (IDHmut 2; 7) time PET selected for further analysis. <b>B,</b> newly diagnosed but not IDHmut indicate higher signal contralateral...
<p>Contralateral TSPO-PET signal elevation is associated with persisting epileptic seizures and worse overall survival. <b>A,</b> Contralateral shows no quantitative difference between patients presenting (<i>n</i> = 20) without at inital diagnosis (top). Significant increase of contralateral TSPO expression in experiencing after treatment the primary tumor site 8) compared to discontinued 12; bottom). <b>B,</b> Heatmap anatomically functionally...
<p>Contralateral TSPO-PET signal elevation is associated with tumor phenotype and localization. <b>A</b> <b>B,</b> Correlation of contralateral signals in patients glioblastoma (<i>n</i> = 38) the (<b>A</b>) volume TSPO-PET, FET-PET (<b>B</b>, left), MRI right). <b>C,</b> Examples images derived from distinct extent TSPO expression PET indicate elevation. <b>D,</b> Overall correlation between...