Gerald Crabtree

Gerald R. Crabtree, MD, Professor, Departments of Pathology and Developmental Biology; Investigator, Howard Hughes Medical Institute, Stanford University School of Medicine

Research description: Dr. Crabtree’s group is interested in the role of signaling by Ca2+-calcineurin-NFAT and its regulation by the Dyrk1a kinase in the development and function of beta cells in the pancreas. He showed that the Ca2+, calcineurin, NFAT signaling pathway was the target of drugs FK506 and cyclosporine. Dr. Crabtree went on to demonstrate the mechanism of action of cyclosporine and FK506 in producing immunosuppression. By making null mutations in the subunits of these complexes they have found that the signaling pathway is essential for heart valve development, vascular development axonal outgrowth and pancreatic beta cell development. They have isolated inhibitors of this pathway, made knock-out mice for each of the components and collaborated effectively with Seung Kim’s laboratory to explore the role of Calcineurin/NFAT/Dyrk1a in regulating the proliferation and function of adult beta cells. This work has had a powerful and sustained influence on studies in the fields of islet biology and diabetes research. His group has also developed synthetic ligands to regulate biologic processes by induced proximity (CIPs). These molecules have been used to activate G-coupled protein receptors and to study biochemical consequences of a specific biochemical event within the cell. His work together has broad implications in the study of normal development and disease. 

Selected relevant publications (Stanford DRC Members in BOLD):

  1. Koh AS, Miller EL, Buenrostro JD, Moskowitz DM, Wang J, Greenleaf WJ, Chang HY, Crabtree GR. Rapid chromatin repression by Aire provides precise control of immune tolerance. Nat Immunol. 2018 Feb;19(2):162-172. doi: 10.1038/s41590-017-0032-8. PMID: 29335648; PMCID: PMC6049828. 

  2. Stanton BZ, Chory EJ, Crabtree GR. Chemically induced proximity in biology and medicine. Science. 2018 Mar 9;359(6380):eaao5902. doi: 10.1126/science.aao5902. PMID: 29590011; PMCID: PMC6417506.