Cross-species transcriptomic signatures predict response to MK2 inhibition in mouse models of chronic inflammation

Summary: Inflammatory bowel diseases (IBDs) are genetically complex and exhibit significant inter-patient heterogeneity in disease presentation and therapeutic response. Here, we show that mouse models of IBD exhibit variable responses to inhibition of MK2, a pro-inflammatory serine/threonine kinase...

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Autores principales:	Lucia Suarez-Lopez, Bing Shui, Douglas K. Brubaker, Marza Hill, Alexander Bergendorf, Paul S. Changelian, Aisha Laguna, Alina Starchenko, Douglas A. Lauffenburger, Kevin M. Haigis
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Immunology Computational bioinformatics Systems biology Transcriptomics Science Q
Acceso en línea:	https://doaj.org/article/76c5639d0d49434cae5abe91c97fbaf5
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spelling	oai:doaj.org-article:76c5639d0d49434cae5abe91c97fbaf52021-11-22T04:28:37ZCross-species transcriptomic signatures predict response to MK2 inhibition in mouse models of chronic inflammation2589-004210.1016/j.isci.2021.103406https://doaj.org/article/76c5639d0d49434cae5abe91c97fbaf52021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221013778https://doaj.org/toc/2589-0042Summary: Inflammatory bowel diseases (IBDs) are genetically complex and exhibit significant inter-patient heterogeneity in disease presentation and therapeutic response. Here, we show that mouse models of IBD exhibit variable responses to inhibition of MK2, a pro-inflammatory serine/threonine kinase, and that MK2 inhibition suppresses inflammation by targeting inflammatory monocytes and neutrophils in murine models. Using a computational approach (TransComp-R) that allows for cross-species comparison of transcriptomic features, we identified an IBD patient subgroup that is predicted to respond to MK2 inhibition, and an independent preclinical model of chronic intestinal inflammation predicted to be non-responsive, which we validated experimentally. Thus, cross-species mouse-human translation approaches can help to identify patient subpopulations in which to deploy new therapies.Lucia Suarez-LopezBing ShuiDouglas K. BrubakerMarza HillAlexander BergendorfPaul S. ChangelianAisha LagunaAlina StarchenkoDouglas A. LauffenburgerKevin M. HaigisElsevierarticleImmunologyComputational bioinformaticsSystems biologyTranscriptomicsScienceQENiScience, Vol 24, Iss 12, Pp 103406- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunology Computational bioinformatics Systems biology Transcriptomics Science Q
spellingShingle	Immunology Computational bioinformatics Systems biology Transcriptomics Science Q Lucia Suarez-Lopez Bing Shui Douglas K. Brubaker Marza Hill Alexander Bergendorf Paul S. Changelian Aisha Laguna Alina Starchenko Douglas A. Lauffenburger Kevin M. Haigis Cross-species transcriptomic signatures predict response to MK2 inhibition in mouse models of chronic inflammation
description	Summary: Inflammatory bowel diseases (IBDs) are genetically complex and exhibit significant inter-patient heterogeneity in disease presentation and therapeutic response. Here, we show that mouse models of IBD exhibit variable responses to inhibition of MK2, a pro-inflammatory serine/threonine kinase, and that MK2 inhibition suppresses inflammation by targeting inflammatory monocytes and neutrophils in murine models. Using a computational approach (TransComp-R) that allows for cross-species comparison of transcriptomic features, we identified an IBD patient subgroup that is predicted to respond to MK2 inhibition, and an independent preclinical model of chronic intestinal inflammation predicted to be non-responsive, which we validated experimentally. Thus, cross-species mouse-human translation approaches can help to identify patient subpopulations in which to deploy new therapies.
format	article
author	Lucia Suarez-Lopez Bing Shui Douglas K. Brubaker Marza Hill Alexander Bergendorf Paul S. Changelian Aisha Laguna Alina Starchenko Douglas A. Lauffenburger Kevin M. Haigis
author_facet	Lucia Suarez-Lopez Bing Shui Douglas K. Brubaker Marza Hill Alexander Bergendorf Paul S. Changelian Aisha Laguna Alina Starchenko Douglas A. Lauffenburger Kevin M. Haigis
author_sort	Lucia Suarez-Lopez
title	Cross-species transcriptomic signatures predict response to MK2 inhibition in mouse models of chronic inflammation
title_short	Cross-species transcriptomic signatures predict response to MK2 inhibition in mouse models of chronic inflammation
title_full	Cross-species transcriptomic signatures predict response to MK2 inhibition in mouse models of chronic inflammation
title_fullStr	Cross-species transcriptomic signatures predict response to MK2 inhibition in mouse models of chronic inflammation
title_full_unstemmed	Cross-species transcriptomic signatures predict response to MK2 inhibition in mouse models of chronic inflammation
title_sort	cross-species transcriptomic signatures predict response to mk2 inhibition in mouse models of chronic inflammation
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/76c5639d0d49434cae5abe91c97fbaf5
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Cross-species transcriptomic signatures predict response to MK2 inhibition in mouse models of chronic inflammation

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