Jörg Menche

Jörg Menche
University of Vienna | UniWien · Zentrum für Molekulare Biologie

Professor

About

140
Publications
19,385
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4,771
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Publications

Publications (140)
Article
Full-text available
Networks offer an intuitive visual representation of complex systems. Important network characteristics can often be recognized by eye and, in turn, patterns that stand out visually often have a meaningful interpretation. In conventional network layout algorithms, however, the precise determinants of a node’s position within a layout are difficult...
Article
Complex disease definitions often represent descriptive umbrella terms of symptoms rather than mechanistic entities. A new study shows how network-based approaches can help identify the mechanisms that link genes, cells, tissues and organs in cardiovascular diseases.
Article
Motivation High-content imaging screens provide a cost-effective and scalable way to assess cell states across diverse experimental conditions. The analysis of the acquired microscopy images involves assembling and curating raw cellular measurements into morphological profiles suitable for testing biological hypotheses. Despite being a critical ste...
Article
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Rare genetic diseases are typically caused by a single gene defect. Despite this clear causal relationship between genotype and phenotype, identifying the pathobiological mechanisms at various levels of biological organization remains a practical and conceptual challenge. Here, we introduce a network approach for evaluating the impact of rare gene...
Article
Full-text available
We report on the hydrothermal polymerization (HTP) of porous polyimide (PI) networks using the medium H 2 O and the comonomers 1,3,5-tris(4-aminophenyl)benzene (TAPB) and pyromellitic acid (PMA).
Article
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The immunological synapse is a complex structure that decodes stimulatory signals into adapted lymphocyte responses. It is a unique window to monitor lymphocyte activity because of development of systematic quantitative approaches. Here we demonstrate the applicability of high-content imaging to human T and natural killer (NK) cells and develop a p...
Preprint
Full-text available
Motivation High-content imaging screens provide a cost-effective and scalable way to assess cell states across diverse experimental conditions. The analysis of the acquired microscopy images involves assembling and curating morphological measurements of individual cells into morphological profiles suitable for testing biological hypotheses. Despite...
Article
Full-text available
Networks provide a powerful representation of interacting components within complex systems, making them ideal for visually and analytically exploring big data. However, the size and complexity of many networks render static visualizations on typically-sized paper or screens impractical, resulting in proverbial ‘hairballs’. Here, we introduce a Vir...
Article
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Invited for this month′s cover is the group of Miriam Unterlass at the Technische Universität Wien and the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences. The image illustrates the synthesis of quinoxalines in “hot water” and the large‐scale computational comparison of all existing syntheses of these quinoxalines. T...
Article
The Front Cover shows the synthesis of various quinoxalines in nothing but “hot water”. Aromatic quinoxalines can be synthesized in down to 10 min from the starting compounds in stoichiometric ratio in water at 230 °C through microwave‐assisted hydrothermal synthesis. The synthetic approach is tolerant to a broad array of functional groups and can...
Article
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Recently, also first HT syntheses (HTS) of organic compounds were achieved. Here, we report the HTS of 2,3‐diarylquinoxalines from 1,2‐diketones and o ‐phenylendiamines ( o ‐PDAs). The synthesis is simple, fast and generates high yields, without requiring any organic solvents, strong acids or toxic catalysts. Reaction times down to <10 min without...
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Obesity-induced white adipose tissue (WAT) hypertrophy is associated with elevated adipose tissue macrophage (ATM) content. Overexpression of the triggering receptor expressed on myeloid cells 2 (TREM2) reportedly increases adiposity, worsening health. Paradoxically, using insulin resistance, elevated fat mass and hypercholesterolemia as hallmarks...
Article
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Adipose tissue macrophages (ATMs) display tremendous heterogeneity depending on signals in their local microenvironment and contribute to the pathogenesis of obesity. The phosphoinositide 3-kinase (PI3K) signalling pathway, antagonized by the phosphatase and tensin homologue (PTEN), is important for metabolic responses to obesity. We hypothesized t...
Preprint
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Solute Carriers (SLCs) represent the largest family of human transporter proteins, consisting of more than 400 members1,2. Despite the importance of these proteins in determining metabolic states and adaptation to environmental changes, a large proportion of them is still orphan and lacks associated substrates1,3,4. Here we describe a systematic ma...
Article
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The WAVE regulatory complex (WRC) is crucial for assembly of the peripheral branched actin network constituting one of the main drivers of eukaryotic cell migration. Here, we uncover an essential role of the hematopoietic-specific WRC component HEM1 for immune cell development. Germline-encoded HEM1 deficiency underlies an inborn error of immunity...
Article
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Multinucleated giant cells (MGCs) are implicated in many diseases including schistosomiasis, sarcoidosis and arthritis. MGC generation is energy intensive to enforce membrane fusion and cytoplasmic expansion. Using receptor activator of nuclear factor kappa-Β ligand (RANKL) induced osteoclastogenesis to model MGC formation, here we report RANKL cel...
Preprint
he detection and neutralization of infected cells and tumors by cytotoxic lymphocytes is a vital immune defense mechanism. The immunological synapse orchestrates the target recognition process and the subsequent cytotoxic activity. Here, we present an integrated experimental and computational strategy to systematically characterize the morphologica...
Chapter
Networks are a general-purpose tool for understanding how the interactions of many components give rise to the behavior of an entire system. Around the turn of the millennium, research inspired by both sociology and statistical physics uncovered intriguing structural commonalities in networks across a wide range of scientific fields. Further resear...
Chapter
From protein interactions to signal transduction, from metabolism to the nervous system: Virtually all processes in health and disease rely on the careful orchestration of a large number of diverse individual components ranging from molecules to cells and entire organs. Networks provide a powerful framework for describing and understanding these co...
Article
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Drug combinations provide effective treatments for diverse diseases, but also represent a major cause of adverse reactions. Currently there is no systematic understanding of how the complex cellular perturbations induced by different drugs influence each other. Here, we introduce a mathematical framework for classifying any interaction between pert...
Article
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Infections induce complex host responses linked to antiviral defense, inflammation, and tissue damage and repair. We hypothesized that the liver, as a central metabolic hub, may orchestrate systemic metabolic changes during infection. We infected mice with chronic lymphocytic choriomeningitis virus (LCMV), performed RNA sequencing and proteomics of...
Preprint
BACKGROUND & AIMS: Genome-wide association studies (GWAS) have uncovered multiple loci associated with inflammatory bowel disease (IBD), yet delineating functional consequences is complex. We used a network-based approach to uncover traits common to monogenic and polygenic forms of IBD in order to reconstruct disease relevant pathways and prioritiz...
Preprint
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Infections induce complex host responses linked to antiviral defense, inflammation and tissue damage and repair. These processes are increasingly understood to involve systemic metabolic reprogramming. We hypothesized that the liver as a central metabolic hub may orchestrate many of these changes during infection. Thus, we investigated the systemic...
Article
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Aberrations in genes coding for subunits of the BRG1/BRM associated factor (BAF) chromatin remodeling complexes are highly abundant in human cancers. Currently, it is not understood how these mostly loss-of-function mutations contribute to cancer development and how they can be targeted therapeutically. The cancer-type-specific occurrence patterns...
Article
Inducing protein degradation via small molecules is a transformative therapeutic paradigm. Although structural requirements of target degradation are emerging, mechanisms determining the cellular response to small-molecule degraders remain poorly understood. To systematically delineate effectors required for targeted protein degradation, we applied...
Article
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Objective: We aim to characterize the causality and molecular and functional underpinnings of HACE1 deficiency in a mouse model of a recessive neurodevelopmental syndrome called spastic paraplegia and psychomotor retardation with or without seizures (SPPRS). Methods: By exome sequencing, we identified 2 novel homozygous truncating mutations in H...
Article
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The histone acetyl reader bromodomain-containing protein 4 (BRD4) is an important regulator of chromatin structure and transcription, yet factors modulating its activity have remained elusive. Here we describe two complementary screens for genetic and physical interactors of BRD4, which converge on the folate pathway enzyme MTHFD1 (methylenetetrahy...
Article
Ph-negative myeloproliferative neoplasms (MPNs) are hematological cancers that can be subdivided into entities with distinct clinical features. Somatic mutations in JAK2, CALR, and MPL have been described as drivers of the disease, together with a variable landscape of nondriver mutations. Despite detailed knowledge of disease mechanisms, targeted...
Preprint
Full-text available
Identification of modules in molecular networks is at the core of many current analysis methods in biomedical research. However, how well different approaches identify disease-relevant modules in different types of gene and protein networks remains poorly understood. We launched the “Disease Module Identification DREAM Challenge”, an open competiti...
Article
Full-text available
We provide a catalog for the effects of the human kinome on cell survival in response to DNA-damaging agents, covering all major DNA repair pathways. By treating 313 kinase-deficient cell lines with ten diverse DNA-damaging agents, including seven commonly used chemotherapeutics, we identified examples of vulnerability and resistance that are kinas...
Article
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Network medicine utilizes common genetic origins, markers and co-morbidities to uncover mechanistic links between diseases. These links can be summarized in the diseasome, a comprehensive network of disease–disease relationships and clusters. The diseasome has been influential during the past decade, although most of its links are not followed up e...
Article
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Probing the dynamic control features of biological networks represents a new frontier in capturing the dysregulated pathways in complex diseases. Here, using patient samples obtained from a pancreatic islet transplantation program, we constructed a tissue-specific gene regulatory network and used the control centrality (Cc) concept to identify the...
Article
Background Myeloproliferative Neoplasms (MPN) encompass several disease subgroups (ET, PV, and PMF) with distinct phenotypic and clinical features. Although the landscape of somatic mutations in MPN has been mapped in detail, the current therapies show limited efficacy in eliminating MPN cells. Immunotherapy for MPN have been suggested as an altern...
Preprint
Full-text available
The histone acetyl-reader BRD4 is an important regulator of chromatin structure and transcription, yet factors modulating its activity have remained elusive. Here we describe two complementary screens for genetic and physical interactors of BRD4, which converge on the folate pathway enzyme MTHFD1. We show that a fraction of MTHFD1 resides in the nu...
Article
Full-text available
The polygenic nature of complex diseases offers potential opportunities to utilize network-based approaches that leverage the comprehensive set of protein-protein interactions (the human interactome) to identify new genes of interest and relevant biological pathways. However, the incompleteness of the current human interactome prevents it from reac...
Preprint
Full-text available
The polygenic nature of complex diseases offers potential opportunities to utilize network-based approaches that leverage the comprehensive set of protein-protein interactions (the human interactome) to identify new genes of interest and relevant biological pathways. However, the incompleteness of the current human interactome prevents it from reac...
Preprint
Full-text available
We provide a catalog for the effects of the human kinome on cell survival in response to DNA damaging agents, selected to cover all major DNA repair pathways. By treating 313 kinase-deficient cell lines with ten diverse DNA damaging agents, including seven commonly used chemotherapeutics, we were able to identify kinase specific vulnerabilities and...
Article
Full-text available
Objectives Bone destruction in rheumatoid arthritis is mediated by osteoclasts (OC), which are derived from precursor cells of the myeloid lineage. The role of the two monocyte subsets, classical monocytes (expressing CD115, Ly6C and CCR2) and non-classical monocytes (which are CD115 positive, but low in Ly6C and CCR2), in serving as precursors for...
Article
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The past decades have witnessed a paradigm shift from the traditional drug discovery shaped around the idea of “one target, one disease” to polypharmacology (multiple targets, one disease). Given the lack of clear-cut boundaries across disease (endo)phenotypes and genetic heterogeneity across patients, a natural extension to the current polypharmac...
Article
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Defects in DNA repair can cause various genetic diseases with severe pathological phenotypes. Fanconi anemia (FA) is a rare disease characterized by bone marrow failure, developmental abnormalities, and increased cancer risk that is caused by defective repair of DNA interstrand crosslinks (ICLs). Here, we identify the deubiquitylating enzyme USP48...
Article
Background -Atherosclerotic cardiovascular disease (heart attacks and strokes) is the major cause of death globally and is caused by the buildup of a plaque in the arterial wall. Genomic data showed that the B cell activating factor receptor (BAFFR) pathway, which is specifically essential for the survival of conventional B lymphocytes (B-2 cells),...
Preprint
Full-text available
The traditional drug discovery paradigm has shaped around the idea of "one target, one disease". Recently, it has become clear that not only it is hard to achieve single target specificity but also it is often more desirable to tinker the complex cellular network by targeting multiple proteins, causing a paradigm shift towards polypharmacology (mul...
Article
Full-text available
Identification of modules in molecular networks is at the core of many current analysis methods in biomedical research. However, how well different approaches identify disease-relevant modules in different types of gene and protein networks remains poorly understood. We launched the “Disease Module Identification DREAM Challenge”, an open competiti...
Article
Background Systems biology methods emerged as popular tools to investigate various types of diseases. However to date, there is a lack of knowledge with regards to their usefulness in rare, Mendelian diseases. In this project, we will use inflammatory bowel disease (IBD) to illustrate the utility of systems biology tools for rare diseases. Methods...
Article
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RNA-dependent RNA polymerases (RdRps) play a key role in the life cycle of RNA viruses and impact their immunobiology. The arenavirus lymphocytic choriomeningitis virus (LCMV) strain Clone 13 provides a benchmark model for studying chronic infection. A major genetic determinant for its ability to persist maps to a single amino acid exchange in the...
Data
Analyses of the L protein of LCMV strain ARM in vitro and in vivo. (A) Two independently generated HeLa S3 CRISPR-Cas9 targeted cell pools per gene of interest for 5 genes were infected in triplicate wells with LCMV ARM WT at a MOI of 0.01 and viral loads were measured at 36 hours post infection by focus forming assay. The obtained data were normal...
Data
Protein functional modules targeted by L protein and other RdRps. (XLSX)
Data
Functional validation of Cl13L-HA virus and HA-immunoprecipitation. (A) HEK293T cells were infected at a MOI of 3 with either Cl13L-HA or with untagged Cl13. Cells were harvested and lysed at 36 hours post infection for western blot analyses with anti-HA antibodies. (B) C57BL/6J mice were infected with 2x106 FFU either Cl13L-HA or untagged Cl13 and...
Data
TRIM21 expression in HEK293T cells infected with Cl13 LCMV. HEK293T cells were infected with LCMV Cl13 WT at a MOI of 3 and harvested at the indicated time points. The gene expression for NP of LCMV and TRIM21 was measured by RT-PCR. The arbitrary units were calculated using HPRT1 as a housekeeping gene, then fold change for each gene was calculate...
Data
Primers used for reverse genetic engineering of L protein-tagged LCMV. (XLSX)
Data
sgRNA oligonucleotide sequences. (XLSX)
Data
Confirmation of the genome editing for CRISPR-Cas9 targeted cells. Confirmation of the genome editing for CRISPR-Cas9 targeted cells using (A) T7EI cleavage assay followed by the band intensity quantification with ImageJ software and (B) Sanger sequencing followed by tracking of indels by decomposition (TIDE) quantification. For TIDE analyses prime...
Data
Host protein interactomes of viral