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Ph.D.University of Colorado, 1986
B.A.University of Colorado, 1978
ChiefLaboratory of Molecular Biology, NIDDK, NIH, 1993–2014
Postdoctoral FellowFred Hutchinson Cancer Research Center, 1986–1992
Scientific Director, Division of Intramural ResearchChief, Laboratory of Molecular Biology, Developmental Biology Section
Specialties: Developmental Biology
Our goal is to be able to describe the postfertilization formation of an organism as a series of switches that regulate gene expression in each cell at the appropriate time and place during development. The relative simplicity of an organism like the worm C. elegans simplifies these studies because of a reduced number of genes and cell types and a rapid embryonic (1 day) and postembryonic (3 days) developmental program. These simple attributes allow us to learn more about developmental processes in individual cells, something that is extremely difficult in more complex animal systems.
We are interested in the transcriptional regulation of cell fate determination during metazoan development. Using the C. elegans system, we exploit forward and reverse genetic approaches to identify and characterize transcription factor function required for proper development of specific cell types, at single-cell resolution. Historically, our interest has primarily been directed at understanding muscle cell specification and differentiation as a model for both embryonic and postembryonic development. Our goal is to fully describe the transcriptional cascade that orchestrates the formation of this tissue from just after fertilization, throughout embryogenesis, and into adulthood.
By understanding the nature and function of master regulatory genes, we can understand the logic behind developmental mechanisms used by all animals, including humans. More importantly, this knowledge allows us to both understand developmental diseases and to manipulate biology to provide therapeutic interventions or cures. For example, we can now generate stem cells from mature tissue samples by expressing a particular combination of master regulatory genes. This type of basic science research is the cornerstone of disease treatment and therapy.
Although we know in general terms the identity and function of several master regulatory genes, we lack a detailed understanding of how these factors orchestrate downstream events at the molecular level. A more detailed understanding is necessary to predict with confidence the full effects of turning on and off master regulators, an issue particularly important for harnessing the power of these genes to regulate developmental events and cure disease.