ArticleScience signaling2018
Integrated in vivo multiomics analysis identifies p21-activated kinase signaling as a driver of colitis.
Article in Science signaling, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- An unexpected tumor-resistant phenotype from floxing PAK1 in a mouse model of colitis associated cancer.Scientific reports · 2025Article
- LKB1 regulates JNK-dependent stress signaling and apoptotic dependency of KRAS-mutant lung cancers.Nature communications · 2025Article
- SRC inhibition enables formation of a growth suppressive MAGI1-PP2A complex in isocitrate dehydrogenase-mutant cholangiocarcinoma.Science translational medicine · 2024Article
- FGFR inhibition blocks NF-ĸB-dependent glucose metabolism and confers metabolic vulnerabilities in cholangiocarcinoma.Nature communications · 2024Article
- Blood transcriptomic markers of necrotizing enterocolitis in preterm pigs.Pediatric research · 2022Article
- Cholesterol Regulates the Tumor Adaptive Resistance to MAPK Pathway Inhibition.Journal of proteome research · 2021Article
- Global characterization of macrophage polarization mechanisms and identification of M2-type polarization inhibitors.Cell reports · 2021Article
- A Novel PAK1-Notch1 Axis Regulates Crypt Homeostasis in Intestinal Inflammation.Cellular and molecular gastroenterology and hepatology · 2021Article
- Chemical Biology Toolkit for DCLK1 Reveals Connection to RNA Processing.Cell chemical biology · 2020Article
- An interspecies translation model implicates integrin signaling in infliximab-resistant inflammatory bowel disease.Science signaling · 2020Article
- Discovery of a selective inhibitor of doublecortin like kinase 1.Nature chemical biology · 2020Article
- Substrate-based kinase activity inference identifies MK2 as driver of colitis.Integrative biology : quantitative biosciences from nano to macro · 2019Article
- Proteogenomic Network Analysis of Context-Specific KRAS Signaling in Mouse-to-Human Cross-Species Translation.Cell systems · 2019Article
- A phenotypic and genomics approach in a multi-ethnic cohort to subtype systemic lupus erythematosus.Nature communications · 2019Article
- Isoform-Specific Destabilization of the Active Site Reveals a Molecular Mechanism of Intrinsic Activation of KRas G13D.Cell reports · 2019Article
- Neutrophil Recruitment: From Model Systems to Tissue-Specific Patterns.Trends in immunology · 2019Review
- Tissue-Specific Oncogenic Activity of KRASCancer discovery · 2019Article
- Mesalamine and azathioprine modulate junctional complexes and restore epithelial barrier function in intestinal inflammation.Scientific reports · 2019Article
- Salmonella stimulates pro-inflammatory signalling through p21-activated kinases bypassing innate immune receptors.Nature microbiology · 2018Article
- Atypical enteropathogenicGut microbesArticle
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
Inflammatory bowel disease (IBD) is a chronic disorder of the gastrointestinal tract that has limited treatment options. To gain insight into the pathogenesis of chronic colonic inflammation (colitis), we performed a multiomics analysis that integrated RNA microarray, total protein mass spectrometry (MS), and phosphoprotein MS measurements from a mouse model of the disease. Because we collected all three types of data from individual samples, we tracked information flow from RNA to protein to phosphoprotein and identified signaling molecules that were coordinately or discordantly regulated and pathways that had complex regulation in vivo. For example, the genes encoding acute-phase proteins were expressed in the liver, but the proteins were detected by MS in the colon during inflammation. We also ascertained the types of data that best described particular facets of chronic inflammation. Using gene set enrichment analysis and trans-omics coexpression network analysis, we found that each data set provided a distinct viewpoint on the molecular pathogenesis of colitis. Combining human transcriptomic data with the mouse multiomics data implicated increased p21-activated kinase (Pak) signaling as a driver of colitis. Chemical inhibition of Pak1 and Pak2 with FRAX597 suppressed active colitis in mice. These studies provide translational insights into the mechanisms contributing to colitis and identify Pak as a potential therapeutic target in IBD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.