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

Periodic Reporting for period 2 - cureCD (Function of long non-coding RNA in Crohn Disease Ulcer Pathogenesis)

Reporting period: 2019-11-01 to 2021-04-30

Crohn’s Disease (CD) is a chronic/relapsing disorders that affect millions of individuals worldwide. Mucosal wounds (ulcers), the hallmark of CD, are the result of complex interactions between microbiota, immune cells, and gut epithelia. Healing of mucosal wounds (ulcers) is associated with better outcomes, but is achieved in less than half of cases. Therefore, there is a critical need to identify tissue specific targets that lead to mucosal healing, to improved outcomes, with minimal adverse effects.
Long non-coding RNAs (lncRNA) are a large and diverse class of non-protein coding genes that exhibit tissue-specific expression and were shown to have key regulatory cellular functions and play a role in regulating immunity and inflammation. We defined several altered lncRNA in CD in both the epithelia and immune cells, and we are building novel model systems to explore their functions in the contexts of their interactions with the microbiota. CD lncRNA, after careful mechanistic exploration, are highly promising targets for potential future intervention with less potential adverse effect due to their tissue specificity.
We have so far defined several altered long non-coding RNAs in Crohn Disease in both the epithelia and immune cells. In parallel, we define gut microbial composition that is more specifically altered in Crohn disease. We are now building novel model systems to explore long non-coding RNAs functions in the contexts of their interactions with the gut microbiota.
Fundamental questions we will try to address in the project include what role do Crohn disease lncRNA play in epithelial differentiation and regeneration? what role do CD lncRNA play in immune activation? How do gut microbial alterations regulate lncRNA expression, and how do dysregulated lncRNA affect mucosal ulcer healing?
Understanding and validating those potential functions will further lead to identifying therapeutic targets for future effective therapies.
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