Gerald Crabtree

Research/Lab website:   Personal Web site

The interests of our laboratory have centered about the origin of biologically specific patterns of transcription and information transfer from the cell membrane to the nucleus. A long-term area of investigation in the laboratory has been a signaling pathway that we discovered a number of years ago in lymphocytes and have recently found is also important for development of the mammalian heart and the functioning of specific neurons in the hippocampus. This signaling pathway involves Ca2+, calcineurin and the NF-ATc family of transcription factors. We have been studying the way that this pathway dictates biologic specificity, even though it is present in most cells.

A second interest in the lab relates to how chromatin is remodeled during development in response to signaling transduction pathways. Here, we have isolated the genes encoding the subunits of a chromatin remodeling complex (The BAF complex) related to the yeast SWI/SNF complex and are gaining insights into how this little machine containing actin and kinesin-like subunits is directed to specific chromosomal loci and how it responds to developmental signals.

Finally, we are developing new ways of making conditional alleles of mammalian genes using synthetic ligands that we hope will bring about a new fusion of biochemical and genetic approaches to understanding and controlling fundamental biologic processes. Here we are creating strains of mice that will allow the rapid and reversible activation or inactivation of any protein during embryonic development or later in life by the simple administration of a small molecule. We hope to use these genetically modified mice to take new approaches to complex developmental questions and studies of memory and learning. In addition, these synthetic ligands or CID (Chemical Induces of Dimerization) are being used by other groups for regulated gene therapy.