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cureCD SIGNED

Function of long non-coding RNA in Crohn Disease Ulcer Pathogenesis

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EC-Contrib. €

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Partnership

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 cureCD project word cloud

Explore the words cloud of the cureCD project. It provides you a very rough idea of what is the project "cureCD" about.

hallmark    informatics    six    relapsing    tissue    pathogenesis    carries    disease    disorders    intervention    therapeutic    microbiome    co    correlations    minimal    strategies    ulcerative    regulate    iuml    plan    protein    mechanistic    ulcers    intestinal    opposing    colitis    limited    interaction    exploration    chronic    critical    healing    ileum    ibd    half    interactions    profiles    nodes    utilize    function    attempts    coding    lncrna    experimental    lab    rnas    expand    regarding    patients    contexts    ve    exhibit    treatment    dysregulation    off    prospectively    collected    prospective    functions    mediating    carful    importently    conserved    rnaseq    diverse    cd    culture    individuals    epithelia    core    immune    cells    inflammatory    epithelial    genes    explore    expression    crohn    mucosal    relative    renewal    human    cellular    deleterious    gut    microbiota    bowel    million    outcomes    granulocytes    uc    understand    guide    biopsies    model    ulcer    pediatric    na    mrnaseq    central    tissues    worldwide    suppress    failed    diseases   

Project "cureCD" data sheet

The following table provides information about the project.

Coordinator		 MEDICAL RESEARCH INFRASTRUCTURE DEVELOPMENT AND HEALTH SERVICES FUND BY THE SHEBA MEDICAL CENTER 

Organization address
address: TEL HASHOMER SHEBA MEDICAL CENTER
city: RAMAT GAN
postcode: 52621
website: http://www.sheba.co.il

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.
 Coordinator Country Israel [IL]
 Total cost 1˙500˙000 €
 EC max contribution 1˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-STG
 Funding Scheme ERC-STG
 Starting year 2018
 Duration (year-month-day) from 2018-05-01   to  2023-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    MEDICAL RESEARCH INFRASTRUCTURE DEVELOPMENT AND HEALTH SERVICES FUND BY THE SHEBA MEDICAL CENTER IL (RAMAT GAN) coordinator 1˙500˙000.00

Map

 Project objective

The Inflammatory Bowel Diseases (IBD), Crohn’s Disease (CD) and Ulcerative Colitis (UC) are chronic/relapsing disorders that affect over six million individuals worldwide. Mucosal ulcers, the hallmark of CD, are the result of a complex interaction between microbiota, immune cells, and gut epithelia. Healing of mucosal ulcers is associated with better outcomes, but is achieved in less than half of cases. Past attempts to suppress central and conserved nodes of the immune system failed due to opposing off-target deleterious effects on epithelial renewal. Therefore, there is a critical need to identify more tissue specific targets that lead to mucosal healing and to improved outcomes.

Using mRNAseq of intestinal biopsies, we identified a widespread dysregulation of long non-coding RNAs (lncRNA) in the ileum of treatment naïve pediatric CD patients. Importently, we identified significant correlations between lncRNA and mucosal ulcers. CD lncRNA, after carful mechanistic exploration, are highly promising targets for potential future intervention as they regulate diverse cellular functions and exhibit a more tissue specific expression in comparison to protein coding genes. The core goal of this proposal is to understand the role of CD lncRNA in ulcer pathogenesis focusing on granulocytes and epithelial functions in the contexts of their interactions with the microbiota.

I plan to utilize state of the art informatics, RNAseq and microbiome profiles together with advanced and novel experimental lab model and co-culture systems, patients-derived prospectively collected tissues, and gut microbiota to explore the role of CD lncRNA function in mediating healing of mucosal ulcers. This work carries the potential to guide new novel therapeutic strategies for mucosal healing with minimal off-targets effects. In a broader prospective, this work will expand our relative limited understanding regarding the role of lncRNA in mediating human diseases.

 Publications

year authors and title journal last update
List of publications.
2019 Yael Haberman, Melanie Schirmer, Phillip J. Dexheimer, Rebekah Karns, Tzipi Braun, Mi-Ok Kim, Thomas D. Walters, Robert N. Baldassano, Joshua D. Noe, Joel Rosh, James Markowitz, Wallace V. Crandall, David R. Mack, Anne M. Griffiths, Melvin B. Heyman, Susan S. Baker, Richard Kellermayer, Dedrick Moulton, Ashish S. Patel, Ajay S. Gulati, Steven J. Steiner, Neal LeLeiko, Anthony Otley, Maria Oliva-He
Age-of-diagnosis dependent ileal immune intensification and reduced alpha-defensin in older versus younger pediatric Crohn Disease patients despite already established dysbiosis
published pages: 491-502, ISSN: 1933-0219, DOI: 10.1038/s41385-018-0114-4 		Mucosal Immunology 12/2 2020-02-13
2019 Nurit Loberman-Nachum, Katya Sosnovski, Ayelet Di Segni, Gilat Efroni, Tzipi Braun, Marina BenShoshan, Lait Anafi, Camila Avivi, Iris Barshack, Dror S. Shouval, Lee A. Denson, Amnon Amir, Ron Unger, Batia Weiss, Yael Haberman
Defining the Celiac Disease Transcriptome using Clinical Pathology Specimens Reveals Biologic Pathways and Supports Diagnosis
published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-019-52733-1 		Scientific Reports 9/1 2020-02-13

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