Puri Fortes. My scientific career has been driven by my passion for RNA. Since predoctoral studies, my goal has been to understand the processing and function of RNA and to apply this knowledge to Biomedicine.
I first studied proteins that bind to RNA to regulate RNA processing (PhD with Dr. Ortín, CNB, Madrid, Spain and postdoc with Dr. Mattaj, EMBL, Heidelberg, Germany). When I got a group leader position (Dpt. Gene Therapy and Hepatology, CIMA/UNAV, Pamplona, Spain) I was excited by the potential of –at that time- recently-discovered short non-coding RNAs (siRNAs and miRNAs) and I used my position and my experience in virology and RNA to (i) identify functional adenovirus miRNAs, (ii) study the function of several miRNAs in different tumors, (iii) develop gene therapy viral vectors that deliver short non-coding RNAs for the treatment of liver diseases and, (iv) develop our own silencing technology based in U1 snRNAs (U1i), which works in vivo and in vitro and when combined with RNAi, results in synergistic inhibitions with therapeutic interest. This project has been recently developed further into a novel mechanism to regulate gene expression.
In the last years, excited about the functional relevance of long non-coding RNAs (lncRNAs), we have identified lncRNAs that respond to viral infection and the antiviral interferon response. When we found that lncRNAs induced by hepatitis C virus were upregulated in hepatocellular carcinoma (HCC) we decided to concentrate our efforts on studying the impact of lncRNAs on HCC initiation and progression with the aim of developing lncRNA-based therapies. We have studied lncRNAs deregulated in cancer, with a special focus in HCC and we have identified several lncRNAs upregulated in HCC whose inhibition with ASOs decreases cell growth in culture and tumor growth in vivo. We are enthusiastic with the possibility that these ASOs can be used for the treatment of HCC.
- Eric Rovira Barreira
- Carlos Hernández Sáez
- Nerea Razquin Erro
- Laura Prats Mari
- Patrick Thenussen Valencia
We have two major proyects in the lab:
1. After the development of our own silencing technology, we have teamed with aptamer experts to build regulatory systems modulated by drugs. Initial experiments indicate that the platform works well and that a pipeline could be developed to extend our system to different therapeutic drugs for biotechnological applications. We believe that combination of aptamer technology and gene expression has great potential for the development of novel RNA-based therapies.
2. The study of lncRNAs deregulated in cancer using TCGA data has shown that lncRNAs are more cancer specific than mRNAs and that many lncRNAs upregulated in cancer are expressed in healthy testis and brain. These results have been also confirmed using transcriptomic data from our own cohort of patientes. We have focused our attention in testis-specific lncRNAs upregulated in cancer as we believe that they may provide tumors with functions related to the excellent capacity of testis to proliferate and copy DNA faithfully. Indeed, both are highly relevant cancer hallmarks. Interestingly, we have identified several lncRNAs upregulated in HCC whose inhibition with ASOs decreases cell growth in culture and tumor growth in vivo. We are enthusiastic with the possibility that these ASOs can be used for the treatment of HCC. We are trying to address the molecular mechanisms induced by these lncRNAs. One of them, called NIHCOLE, is required to help the DNA damage machinery to increase the efficiency of ligation of DNA breaks. We hope that NIHCOLE inhibition by antisense oligonucleotides linked to the beads used for trans-arterial radio embolization could reach the clinical setting.