Abstract

In recent years, we have shown that class IIa HDACs are important therapeutic targets in certain cancers. We know that class IIa HDACs control H3K27 acetylation status at TE and SE, but we do not know how these distal regulatory elements control gene expression and we do not have information about the reciprocal influences of 3D genome organization. In addition, there is an urgent need to develop new selective class IIa HDACs inhibitors to translate our discoveries into the clinic. With this project, we aim to gain further insight into the role of class IIa in epigenome control and identify new and more effective class IIa HDACs inhibitors.

The project is organized in 3 different work packages (WP). Two of them are experimental and aim at answering the open questions mentioned above, while the last one focuses on the dissemination of the results. Two different cancer models are used for the in vivo validations: 1) leiomyosarcoma (LMS), a rare and highly aggressive tumor in which class IIa HDACs play a key role (); 2) colorectal carcinoma (CRC), in this case patient-derived organoids guarantee the advantage to evaluate the role of the 3D microenvironment. Uterine smooth muscle cells (UtSMC) and normal colon epithelial cells (NCE) are used as reference for normal tissue.

Partenariato

• Università degli studi di Udine
• Università Sapienza Roma, Dipartimento Chim. e Tecn. del Farmaco
• Università Ca’Foscari Venezia, Department of Molecular Sciences and Nanosystems

Importo del progetto

Importo totale del progetto        Euro 67.415,00
Importo del progetto Uniud        Euro 60.561,00
Finanziamento Uniud                Euro 6.854,00

Durata

• Dal 03.02.2025
• Al 02.02.2027

Link

https://prin.mur.gov.it/