I did a PhD and first postdoc in Theoretical Physics (1995-2001), during which I published 15 articles in peer-reviewed Physics journals, which accumulate more than 1000 citations. In 2001, the publication of the draft of the human genome encouraged me to explore other areas of research. I then joined the Sanger Institute (2001-2004), where I developed one of the first computational methods to predict alternative splicing variants from EST data (Eyras et al. 2004), and participated in the landmark papers on the annotation and analysis of the mouse and rat genomes. During 2004 I contributed to the analyses of the conservation of alternative splicing in vertebrates and mammals as part of the chicken (Nature 2004) and cow (Science 2009) genome publications. In January 2005 I was appointed ICREA Research Professor at the UPF.
Since the early days of my independent career (2005- onwards), I worked on several aspects of alternative splicing, including evolution, mechanisms of regulation and relation to disease. My group described how transposable elements influence splicing regulation (Corvelo et al. 2008) and the evolution of SR proteins (Plass et al. 2008). My group also developed computational methods to predict splicing regulatory signals (Corvelo et al. 2010) and the effect on splicing of RNA secondary structures (Plass et al. 2011).
During the last years, my group has focused on the development of analysis tools for high-throughput sequencing data (Althammer et al. 2011, Sebestyén et al. 2014, Alamancos et al. 2015), which allowed us to make important contributions in the understanding of gene regulation through multiple collaborations. One of them, during a research stay of 3 months in Toronto University in 2013, funded by the Spanish Ministry of Education (Raj et al. Mol Cell 2014). More recently, my group collaborated with other scientists to propose a novel mechanism of regulation of alternative splicing through the binding of Argonaute proteins to intragenic transcriptional enhancers (Alló et al. PNAS 2014).
Current focus of my research group is to study the role of RNA processing alterations in cancer. We have recently performed one of the first exhaustive analyses of splicing alterations using multiple cancer types (Sebestyen et al. 2015, Sebestyén et al. 2016). We have described alterations in splicing factors and alternative splicing events related to cell proliferation (Sebestyén et al. 2016), cancer progression, and metastasis (Trincado et al. 2016). We have also recently described that splicing changes in cancer recapitulate the functional impacts of cancer mutations (Climente-Gonzalez et al. 2017). We now plan to develop tools to identify those alterations with potential therapeutic relevance, with the overall goal of contributing to current cancer genomic strategies of prognosis and therapy selection.