Imperial College London

ProfessorMichaelJohnson

Faculty of MedicineDepartment 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{Johnson:2015:10.1038/ncomms7031,
author = {Johnson, MR and Behmoaras, J and Bottolo, L and Krishnan, ML and Pernhorst, K and Santoscoy, PL and Rossetti, T and Speed, D and Srivastava, PK and Chadeau-Hyam, M and Hajji, N and Dabrowska, A and Rotival, M and Razzaghi, B and Kovac, S and Wanisch, K and Grillo, FW and Slaviero, A and Langley, SR and Shkura, K and Roncon, P and De, T and Mattheisen, M and Niehusmann, P and O'Brien, TJ and Petrovski, S and von, Lehe M and Hoffmann, P and Eriksson, J and Coffey, AJ and Cichon, S and Walker, M and Simonato, M and Danis, B and Mazzuferi, M and Foerch, P and Schoch, S and De, Paola V and Kaminski, RM and Cunliffe, VT and Becker, AJ and Petretto, E},
doi = {10.1038/ncomms7031},
journal = {Nat Commun},
title = {Systems genetics identifies Sestrin 3 as a regulator of a proconvulsant gene network in human epileptic hippocampus.},
url = {http://dx.doi.org/10.1038/ncomms7031},
volume = {6},
year = {2015}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Gene-regulatory network analysis is a powerful approach to elucidate the molecular processes and pathways underlying complex disease. Here we employ systems genetics approaches to characterize the genetic regulation of pathophysiological pathways in human temporal lobe epilepsy (TLE). Using surgically acquired hippocampi from 129 TLE patients, we identify a gene-regulatory network genetically associated with epilepsy that contains a specialized, highly expressed transcriptional module encoding proconvulsive cytokines and Toll-like receptor signalling genes. RNA sequencing analysis in a mouse model of TLE using 100 epileptic and 100 control hippocampi shows the proconvulsive module is preserved across-species, specific to the epileptic hippocampus and upregulated in chronic epilepsy. In the TLE patients, we map the trans-acting genetic control of this proconvulsive module to Sestrin 3 (SESN3), and demonstrate that SESN3 positively regulates the module in macrophages, microglia and neurons. Morpholino-mediated Sesn3 knockdown in zebrafish confirms the regulation of the transcriptional module, and attenuates chemically induced behavioural seizures in vivo.
AU - Johnson,MR
AU - Behmoaras,J
AU - Bottolo,L
AU - Krishnan,ML
AU - Pernhorst,K
AU - Santoscoy,PL
AU - Rossetti,T
AU - Speed,D
AU - Srivastava,PK
AU - Chadeau-Hyam,M
AU - Hajji,N
AU - Dabrowska,A
AU - Rotival,M
AU - Razzaghi,B
AU - Kovac,S
AU - Wanisch,K
AU - Grillo,FW
AU - Slaviero,A
AU - Langley,SR
AU - Shkura,K
AU - Roncon,P
AU - De,T
AU - Mattheisen,M
AU - Niehusmann,P
AU - O'Brien,TJ
AU - Petrovski,S
AU - von,Lehe M
AU - Hoffmann,P
AU - Eriksson,J
AU - Coffey,AJ
AU - Cichon,S
AU - Walker,M
AU - Simonato,M
AU - Danis,B
AU - Mazzuferi,M
AU - Foerch,P
AU - Schoch,S
AU - De,Paola V
AU - Kaminski,RM
AU - Cunliffe,VT
AU - Becker,AJ
AU - Petretto,E
DO - 10.1038/ncomms7031
PY - 2015///
TI - Systems genetics identifies Sestrin 3 as a regulator of a proconvulsant gene network in human epileptic hippocampus.
T2 - Nat Commun
UR - http://dx.doi.org/10.1038/ncomms7031
UR - http://www.ncbi.nlm.nih.gov/pubmed/25615886
UR - http://hdl.handle.net/10044/1/21203
VL - 6
ER -