The Neilson laboratory's primary goal is to better understand how post-transcriptional gene regulation impacts mammalian development and disease. We are particularly interested in the role of the 3' untranslated region in gene expression, and how alternative cleavage and polyadenylation influences the visibility of messenger RNA transcripts to regulatory factors such as microRNAs and RNA binding proteins. The laboratory is actively pursuing answers to the following four questions:
- How do programs of cleavage and polyadenylation change during cellular development or in a disease state?
- How does alternative cleavage and polyadenylation impact expression of individual genes and overall cellular physiology?
- hat cis-elements and trans-factors are involved in the conditional regulation of genes characterized by alternative cleavage and polyadenylation programs?
- How are programs of alternative cleavage and polyadenylation controlled?
We employ a variety of approaches in the pursuit of these questions, ranging from high throughput sequencing-based transcriptomics to classical molecular and cellular analysis of gene-specific events to construction of mouse mutants where our hypotheses can be modeled and tested in vivo. Our current studies are in the context of primary and transformed cells of the mammalian immune system.