My research interests involve understanding the molecular interactions of signal transduction pathways that are necessary to convert extracellular signals into transcription outputs. My current work focuses on the Notch signaling pathway, specifically the nuclear effector CSL. Notch signaling is a conserved pathway of cellular differentiation in metazoans and aberrant Notch signaling is associated with neural disorders, developmental defects, and cancer. CSL is a DNA-bound transcription factor that is required for both repression and activation of Notch target genes. The control of transcription by CSL is thought to occur through CSL-mediated protein-protein interactions with specific coregulator proteins. In the absence of an extracellular signal, CSL binds corepressor proteins such as N-Cor/SMRT and CIR which results in transcriptional silencing. Upon pathway activation, the intracellular domain of the receptor Notch translocates to the nucleus and binds CSL, which results in the displacement of corepressors from CSL. The Notch-CSL complex additionally recruits the coactivators PCAF/GCN5 and Mastermind to upregulate transcription.

My laboratory uses x-ray crystallography to determine structures for CSL bound to coregulators, and biochemical techniques to characterize and recapitulate the interactions of these components in vitro. Concurrent with this work is the verification of our models and hypotheses using in vivo model systems. Ultimately, the goal of this research is to provide a molecular explanation for the mechanisms that control CSL-mediated transcription. This work is critical to the understanding of Notch signaling in normal biological contexts and in diseased states such as cancer.