During my PhD I studied the alternative splicing pathways of CD44 in human breast cells, showing that one of these pathways is de-regulated in ductal carcinomas. I then performed my post-doctoral research in Adrian R. Krainer Lab at Cold Spring Harbor Laboratory, New York (USA). There I investigated the basic mechanisms of 5' splice-site selection in humans using a combination of molecular, genomic and computational approaches. I also functionally characterized splicing mutations causing various genetic diseases, such as metabolic, neurological and muscular disorders. My major finding is the unexpected flexibility in the recognition of 5' splice sites by the U1 small nuclear RNA, which challenged a long-standing dogma and holds important implications for disease-causing splicing mutations and alternative splicing.