Research Interests

 

The development and proper functioning of a multicellular animal rely on communication between cells. The molecular details that drive these cellular events are gradually being discovered through the combined efforts of researchers around the world. In many cases what we have learned about these processes has contributed to our understanding of human diseases in which specific forms of cellular communication are compromised. The molecular pathways that mediate cellular communication have been remarkably conserved over the course of evolution, meaning that what is learned from simple model systems can be directly applied to more complex systems, such as humans. In my laboratory, we use the popular genetic model system Caenorhabditis elegans, which is a free-living nematode worm that undergoes a well-characterized development from fertilized egg to a mature adult of 959 cells, including digestive, muscle, reproductive, and nervous systems. A large number of cell communication events are critical to the worm's proper development, and we are focusing on a subset of these, known as Notch signaling events. Worms that have mutations in the Notch pathway genes have dramatic developmental defects, and we study these defects as a way of learning about the role and the molecular details of Notch signaling. Using classical genetic and molecular genetic approaches, the experiments in my lab are geared toward discovering new players in the Notch signaling pathway and then deciphering their specific function within the framework of a particular developmental event. The characterization of two genes, aph-1 and aph-2, has led us to an essential step in Notch signaling events in which the Notch Receptor protein is cleaved within its transmembrane domain. This cleavage is accomplished by a collection of proteins known as the gamma-secretase complex, also known to cleave other transmembrane proteins, including the amyloid precursor protein involved in Alzheimer's Disease. The four core components of the gamma-secretase complex are APH-1, APH-2/Nicastrin, PEN-2, and presenilins; we are currently experimenting with genetically modifying the activity of these genes in hopes of better understand their specific roles in the context of Notch signaling events that are important for C. elegans development.