We are interested in the regulation of alternative pre-mRNA splicing, its contribution to cell function and development, and its disruption in disease. By generating different arrangements of exon sequences, alternative splicing enables a single gene to encode a family of proteins with variations in structure and functional properties. This allows the size of the proteome to greatly exceed the number of genes and contributes to greater organismal complexity. Alternative splicing patterns can be regulated developmentally and in response to physiological conditions to exert quantitative and qualitative control over gene expression.
Disruptions of pre-mRNA splicing are important contributors to inherited disease and cancer. Nevertheless, the mechanisms by which splicing is regulated and integrated with other developmental and physiological control mechanisms are understood poorly. A better understanding of these mechanisms is important for the development of diagnostic, prognostic and therapeutic tools.
We also study the function, processing and evolution of large introns, which are found in genes with important roles in development and disease. Large introns can take hours or days to be transcribed and may help to ensure correct timing of gene expression during development. Large introns may also modulate recombination rates to reduce interference selection between sites on flanking exons.
We approach these problems through a combination of genetics, molecular biology, biochemistry and bioinformatics applied to Drosophila and mammalian models.
A. Javier Lopez, Ph.D.
Office: Mellon Institute 217C