Principal Investigator: Lab Chief: Alessia Pascale Lab Staff: Annalisa Barbieri, Nicoletta Marchesi Scientific Consultant: Stefano Govoni

Diabetic retinopathy (RD) is a neurodegenerative pathology affecting the retina and evolving in irreversible visual impairment in the elderly.
New vessels formation mediated by VEGF-A (vascular endothelial growth factor A), as well as chronic inflammation involving TNFα (tumor necrosis factor α) have a detrimental role in DR development and progression.
The project is based on an innovative strategy: to modify the amount of key cellular proteins acting through a new class of proteins named ELAV. The RNA-binding ELAV proteins family interacts with specific sequences within target mRNAs, mainly positively affecting their stability and/or rate of translation into protein. Among the ELAV proteins, HuR is the member that plays a crucial role in RD, as we previously demonstrated. Of interest, VEGF-A and TNFα transcripts are both targeted by HuR. Therefore, the inhibition of HuR activity may represent a novel strategy to counteract new vessels formation and inflammation during RD development and progression.
Through an in silico approach, the project is aimed at discovering compounds able to destroy the interaction of HuR with the target mRNA. Subsequently, the biological activity of the selected compounds will be evaluated on ad hoc cellular models mimicking the conditions encountered in the course of DR.

Recent Publications:

• “THE PKCβ/HUR/VEGF PATHWAY IN DIABETIC RETINOPATHY”. Amadio M., Bucolo C., Leggio G.M., Drago F., Govoni S. and Pascale A. Biochem. Pharmacol. 80: 1230-1237, 2010.
• “INDUCTION OF VEGFA mRNA TRANSLATION BY CoCl2 MEDIATED BY HUR”. Osera C., Martindale J.L., Amadio M., Kim J., Yang X., Moad C.A., Indig F.E., Govoni S., Abdelmohsen K., Gorospe M., Pascale A. RNA Biol. 12(10):1121-30, 2015.
• “NANOSYSTEMS BASED ON siRNA SILENCING HUR EXPRESSION COUNTERACT DIABETIC RETINOPATHY IN RAT”. Amadio M., Pascale A.*, Cupri S., Pignatello R., Osera C., D’Agata V., D’Amico A.G., Leggio G.M., Ruozi B., Govoni S., Drago F., Bucolo C. Pharmacol Res.111:713-20, 2016. *co-authorship

Links:
http://dipsf.unipv.eu/site/home/research.html
https://www.researchgate.net/profile/Alessia_Pascale