Much of our work is concerned with LIN-12/Notch, the receptor component of one of the major signaling systems for specifying cell fate during animal development. Mutations in core components and modulators of the LIN-12/Notch pathway have been implicated in cancer, Alzheimer's disease, and other diseases and syndromes. Using C. elegans , we study how LIN-12/Notch signaling is modulated during normal development and identify potential ways it may be modulated to combat disease.
In our developmental studies, we aim to understand the fundamental logic and molecular events that govern cell fate decision-making. We mainly study two simple cell fate decision paradigms: the "AC/VU decision" and "VPC fate specification." These simple paradigms offer the opportunity to apply powerful methods of genetic analysis to fundamental mechanisms of cell fate specification that operate in all animals. During these events, different modulatory mechanisms regulate LIN-12/Notch activity and different signaling inputs are integrated so that correct cell fate decisions are made.
We also use sensitive and specific suppressor and enhancer screens in C. elegans for "gene discovery" with the aim of identifying new, conserved modulators of LIN-12/Notch and other signaling pathways.
In more recent extensions of our work, our studies of regulatory circuitry in the AC/VU decision have led us to study programming and reprogramming of cell fate in gonadogenesis, and our studies of signaling integration in VPC fate specification have stimulated our interest in biosensors for signaling pathway activity. We are also studying how signal transduction is modulated in dauer larvae, a natural state of prolonged developmental arrest that allows worms to survive harsh environmental conditions.