My research focuses on the study of the mechanisms of pre-messenger RNA splicing in human cells. Splicing is the process by which introns are excised and exons are joined together, and is essential for the correct expression of genes. The relevance of splicing in the big picture is further illustrated by these two facts: (1) a large fraction (~50%) of point mutations causing human hereditary disease and cancer affect splicing, and other syndromes are caused by alterations of splicing factors; (2) alternative splicing affects >90% of genes in the human genome, is critical to explain the complexity of the human transcriptome and proteome, and contributes to many processes at a cellular and organismal level. The molecular and phenotypic consequences of many disease-causing mutations at splicing elements are not predictable at present, and the mechanisms of alternative splicing and their impact on other biological processes are still largely unknown. These limitations stress the need to further understand the basic mechanisms of splicing. In my lab I address such type of questions by using a combination of computational, molecular and cell biology methods. The two long-term goals of my research are to improve the molecular diagnosis of splicing mutations causing human genetic disease and to elucidate the role of alternative splicing events in their biological contexts. In the future I also hope to identify new therapeutic targets, and/or to develop RNA-based therapies for human diseases
