Cross-species transcriptomic signatures predict response to MK2 inhibition in mouse models of chronic inflammation
Name
PIIS2589004221013778.pdf
Description
Published version
Size
4.2 MB
Format
Adobe PDF
Checksum (MD5)
c962e7a2d0210a74129d2f6f9e5a63dd
Author(s)
Suarez-Lopez, Lucia
Shui, Bing
Brubaker, Douglas K
Hill, Marza
Bergendorf, Alexander
Changelian, Paul S
Laguna, Aisha
Starchenko, Alina
Lauffenburger, Douglas A
Haigis, Kevin M
Date Issued
2021
Journal
iScience
Publisher
Elsevier BV
Citation
Suarez-Lopez, Lucia, Shui, Bing, Brubaker, Douglas K, Hill, Marza, Bergendorf, Alexander et al. 2021. "Cross-species transcriptomic signatures predict response to MK2 inhibition in mouse models of chronic inflammation." iScience, 24 (12).
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.ISCI.2021.103406
