Alternative splicing, the process by which a single gene can give rise to multiple, distinct protein isoforms, affects the vast majority of human genes. This mechanism enormously increases the complexity of eukaryotic genomes, and plays important roles in many human diseases.

We use high-throughput genomics, sequence analysis, and molecular genetics to study the mechanistic origins and phenotypic consequences of alternative splicing and other RNA processing. A typical experiment might combine next-generation sequencing to identify a molecular phenotype with minigene experiments to test specific biochemical predictions.

Current questions of interest include:

• What roles does alternative splicing play in non-malignant disorders of the blood?
• Does dysregulated RNA processing facilitate solid tumor formation and therapeutic resistance?
• How can RNA processing modulate the severity of human genetic disease?

We also study transcriptional regulation, with a focus on the origins of genome-wide transcription factor binding.