Application of pharmacogenomics and bioinformatics to exemplify the utility of human ex vivo organoculture models in the field of precision medicine

Karen Cowan (Lead / Corresponding author), Graeme MacLuskie, Michael Finch, Colin N. A. Palmer, Jane Hair, Max Bylesjo, Sarah Lynagh, Pamela Brankin, Marian McNeil, Carolyn Low, David Mallinson, Elaine M. Gourlay, Hannah Child, Linda Cheyne, David C. Bunton

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Abstract

Here we describe a collaboration between industry, the National Health Service (NHS) and academia that sought to demonstrate how early understanding of both pharmacology and genomics can improve strategies for the development of precision medicines. Diseased tissue ethically acquired from patients suffering from chronic obstructive pulmonary disease (COPD), was used to investigate inter-patient variability in drug efficacy using ex vivo organocultures of fresh lung tissue as the test system. The reduction in inflammatory cytokines in the presence of various test drugs was used as the measure of drug efficacy and the individual patient responses were then matched against genotype and microRNA profiles in an attempt to identify unique predictors of drug responsiveness. Our findings suggest that genetic variation in CYP2E1 and SMAD3 genes may partly explain the observed variation in drug response.

Original languageEnglish
Article numbere0226564
Pages (from-to)1-15
Number of pages15
JournalPLoS ONE
Volume14
Issue number12
DOIs
Publication statusPublished - 20 Dec 2019

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    Cowan, K., MacLuskie, G., Finch, M., Palmer, C. N. A., Hair, J., Bylesjo, M., Lynagh, S., Brankin, P., McNeil, M., Low, C., Mallinson, D., Gourlay, E. M., Child, H., Cheyne, L., & Bunton, D. C. (2019). Application of pharmacogenomics and bioinformatics to exemplify the utility of human ex vivo organoculture models in the field of precision medicine. PLoS ONE, 14(12), 1-15. [e0226564]. https://doi.org/10.1371/journal.pone.0226564