Developing novel epigenetic advanced therapies for the treatment of cardiac fibrosis

The University of Navarra (UNAV) is a non-profit private university founded in 1952 based in Pamplona, Spain. It confers 56 official degrees and administers more than 90 postgraduate programs (including 20 doctoral programs and 42 master’s programs) through 10 schools, two superior colleges, the IESE Business School and its 5 comprehensive Research Centres: CCUN (Cancer Centre Clínica Universidad de Navarra), BIOMA (Biodiversity and Environment Institute) and DATAI (Institute of Data Science and Artificial Intelligence), ICS (INSTITUTE FOR CULTURE AND SOCIETY and CIN (Centre for Nutrition Research).
UNAV has more than 14.000 students in 5 campuses: Pamplona, San Sebastian, Madrid, Barcelona and New York with a wide network of international universities and research centres.
UNAV has a sound track record in participating in European Research Programs. The university has participated in 126 European projects from FP4 to Horizon Europe, including LIFE, ERASMUS+ and INTERREG Programs; of which 22 projects were coordinated by the university. The University also counts with a thorough experience in MSCA and ERC grants with over 26 signed grants.
UNAV been awarded with the HR Excellence in Research quality seal (HRS4R) that guarantees the implementation of the European Charter for Researchers and the Code of Conduct for the Recruitment of Researchers.

OFFER DESCRIPTION

Cardiac disease is usually driven by adverse remodeling and fibrotic scar formation, and represents the main cause of mortality and morbidity worldwide. An effective anti-fibrotic treatment is not yet clinically available although promising advances are being made by research of new epigenetic therapies.
By performing CRISPR perturbation, transcriptomics and ex vivo functional assays in primary cardiac fibroblasts, our group has identified key chromatin factors responsible for the fibrotic processes. These factors could be pharmacologically targeted to control cardiac fibrosis.
In view of our previous results, we aim to develop a first-in-class epigenetic-based therapeutics that will effectively treat the disease by reversing fibrotic scarring in the heart. Specific anti-fibrotic chemical molecules will be identified by in silico studies and liposome-encapsulated for optimal delivery to the heart. Alternatively, functionalized nano-based siRNA delivery systems will be developed with the aim to target the activated cardiac fibroblasts and reverse their pro-fibrotic profile. After initial in vitro selection and validation of the different particles, the biodistribution and heart´s retention of the most active ones will be assessed in a mouse model of myocardial infarct. Next, as a first pre-clinical approach, the best anti-fibrotic particles will be tested in human cardiac organoids that greatly resemble the damaged heart, as well as in a pig model of cardiac disease.
The project is expected to provide proof of concept anti-fibrotic approaches for future clinical translation. The already approved GMP production of the biomaterials and molecules will facilitate the implementation of the developed technology into the clinics.