Imperial College London
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ProfessorMichaelJohnson

Faculty of Medicine, Department of Brain Sciences

Professor of Neurology and Genomic Medicine
 
 
 
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Contact

 

m.johnson Website

 
 
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Location

 

E419Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Srivastava:2018:10.1038/s41467-018-06008-4,
author = {Srivastava, P and van, Eyll J and Godard, P and Manuela, M and Delahaye-Duriez, A and Van, Steenwinckel J and Gressens, P and Danis, B and Vandenplas, C and Patrik, F and Leclercq, K and Mairet-Coello, G and Cardenas, A and Vanclef, F and Laaniste, L and Niespodziany, I and Keaney, J and Gasser, J and Gillet, G and Shkura, K and Chong, S-A and Behmoaras, J and Kadiu, I and Petretto, EG and Kaminski, R and Johnson, M},
doi = {10.1038/s41467-018-06008-4},
journal = {Nature Communications},
title = {A systems-level framework for drug discovery identifies Csf1R as an anti-epileptic drug target},
url = {http://dx.doi.org/10.1038/s41467-018-06008-4},
volume = {9},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The identification of drug targets is highly challenging, particularly for diseases of the brain. To address this problem, we developed and experimentally validated a general computational framework for drug target discovery that combines gene regulatory information with causal reasoning (“Causal Reasoning Analytical Framework for Target discovery”—CRAFT). Using a systems genetics approach and starting from gene expression data from the target tissue, CRAFT provides a predictive framework for identifying cell membrane receptors with a direction-specified influence over disease-related gene expression profiles. As proof of concept, we applied CRAFT to epilepsy and predicted the tyrosine kinase receptor Csf1R as a potential therapeutic target. The predicted effect of Csf1R blockade in attenuating epilepsy seizures was validated in three pre-clinical models of epilepsy. These results highlight CRAFT as a systems-level framework for target discovery and suggest Csf1R blockade as a novel therapeutic strategy in epilepsy. CRAFT is applicable to disease settings other than epilepsy.
AU  - Srivastava,P
AU  - van,Eyll J
AU  - Godard,P
AU  - Manuela,M
AU  - Delahaye-Duriez,A
AU  - Van,Steenwinckel J
AU  - Gressens,P
AU  - Danis,B
AU  - Vandenplas,C
AU  - Patrik,F
AU  - Leclercq,K
AU  - Mairet-Coello,G
AU  - Cardenas,A
AU  - Vanclef,F
AU  - Laaniste,L
AU  - Niespodziany,I
AU  - Keaney,J
AU  - Gasser,J
AU  - Gillet,G
AU  - Shkura,K
AU  - Chong,S-A
AU  - Behmoaras,J
AU  - Kadiu,I
AU  - Petretto,EG
AU  - Kaminski,R
AU  - Johnson,M
DO  - 10.1038/s41467-018-06008-4
PY  - 2018///
SN  - 2041-1723
TI  - A systems-level framework for drug discovery identifies Csf1R as an anti-epileptic drug target
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-018-06008-4
UR  - http://hdl.handle.net/10044/1/62827
VL  - 9
ER  -
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