cureCD SIGNED
Function of long non-coding RNA in Crohn Disease Ulcer Pathogenesis
Total Cost €
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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 contact info |
| 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.
| # | ||||
|---|---|---|---|---|
| 1 | MEDICAL RESEARCH INFRASTRUCTURE DEVELOPMENT AND HEALTH SERVICES FUND BY THE SHEBA MEDICAL CENTER | IL (RAMAT GAN) | coordinator | 1˙500˙000.00 |
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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 |
|---|---|---|---|
| 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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