Crabtree earned his B.S. in Chemistry and Mathematics from Western Liberty State College and his M.D. from Temple University. While at medical school, he became interested in laboratory research and started to work at Dartmouth College with Allan Munck on the biochemistry of steroid hormones. Studying gene regulation, he discovered hepatocyte nuclear factor 1 and started to focus on nuclear gene regulation.
After a short stint at the NIH, he started his lab at Stanford in 1985. Using T lymphocytes as a model system, he discovered the nuclear factor of activated T cells (NFAT).[2] Furthermore, he found that cyclosporine inhibits NFAT assembly. Teaming up with Stuart Schreiber from Harvard University, they began to study the calcium-calcineurin-NFAT pathway essential to function of the immune system and vertebrate development including neural and heart development.
Crabtree's lab now focuses on understanding chromatin regulation in stem cells and using small molecules to influence protein-protein interactions that govern embryonic development. He has been a Howard Hughes Medical Institute (HHMI) investigator since 1987. He was induced into the National Academy of Science in 1997 and is a Fellow of the American Association for the Advancement of Science.