Imperial College London
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ProfessorJessicaStrid

Faculty of Medicine, Department of Immunology and Inflammation

Professor of Cellular Immunology
 
 
 
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Contact

 

+44 (0)20 3313 1475j.strid

 
 
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Location

 

9N15BCommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Duggan:2018:10.1016/j.jcmgh.2018.01.012,
author = {Duggan, SP and Garry, C and Behan, FM and Phipps, S and Kudo, H and Kirca, M and Zaheer, A and McGarrigle, S and Reynolds, JV and Goldin, R and Kalloger, SE and Schaeffer, DF and Long, A and Strid, J and Kelleher, D},
doi = {10.1016/j.jcmgh.2018.01.012},
journal = {Cellular and Molecular Gastroenterology and Hepatology},
pages = {569--590},
title = {siRNA library screening identifies a druggable immune-signature driving esophageal adenocarcinoma cell growth},
url = {http://dx.doi.org/10.1016/j.jcmgh.2018.01.012},
volume = {5},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background & Aims: Effective therapeutic approaches are urgently required to tackle the alarmingly poor survival outcomes in esophageal adenocarcinoma (EAC) patients. EAC originates from within the intestinal-type metaplasia, Barrett’s esophagus, a condition arising on a background of gastroesophageal reflux disease and associated inflammation.Methods:This study used a druggable genome small interfering RNA (siRNA) screening library of 6022 siRNAs in conjunction with bioinformatics platforms, genomic studies of EAC tissues, somatic variation data of EAC from The Cancer Genome Atlas data of EAC, and pathologic and functional studies to define novel EAC-associated, and targetable, immune factors.Results:By using a druggable genome library we defined genes that sustain EAC cell growth, which included an unexpected immunologic signature. Integrating Cancer Genome Atlas data with druggable siRNA targets showed a striking concordance and an EAC-specific gene amplification event associated with 7 druggable targets co-encoded at Chr6p21.1. Over-representation of immune pathway–associated genes supporting EAC cell growth included leukemia inhibitory factor, complement component 1, q subcomponent A chain (C1QA), and triggering receptor expressed on myeloid cells 2 (TREM2), which were validated further as targets sharing downstream signaling pathways through genomic and pathologic studies. Finally, targeting the triggering receptor expressed on myeloid cells 2-, C1q-, and leukemia inhibitory factor–activated signaling pathways (TYROBP–spleen tyrosine kinase and JAK-STAT3) with spleen tyrosine kinase and Janus-activated kinase inhibitor fostamatinib R788 triggered EAC cell death, growth arrest, and reduced tumor burden in NOD scid gamma mice.Conclusions:These data highlight a subset of genes co-identified through siRNA targeting and genomic studies of expression and somatic variation, specifically highlighting the contribution that immune-related fac
AU  - Duggan,SP
AU  - Garry,C
AU  - Behan,FM
AU  - Phipps,S
AU  - Kudo,H
AU  - Kirca,M
AU  - Zaheer,A
AU  - McGarrigle,S
AU  - Reynolds,JV
AU  - Goldin,R
AU  - Kalloger,SE
AU  - Schaeffer,DF
AU  - Long,A
AU  - Strid,J
AU  - Kelleher,D
DO  - 10.1016/j.jcmgh.2018.01.012
EP  - 590
PY  - 2018///
SN  - 2352-345X
SP  - 569
TI  - siRNA library screening identifies a druggable immune-signature driving esophageal adenocarcinoma cell growth
T2  - Cellular and Molecular Gastroenterology and Hepatology
UR  - http://dx.doi.org/10.1016/j.jcmgh.2018.01.012
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000431058800007&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/60178
VL  - 5
ER  -
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