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.
[10] Later his laboratory used genetic approaches in mice to show that calcineurin-NFAT signaling plays essential roles in the development of many vertebrate organ systems[11] and its dysregulation is likely to be responsible for many of the phenotypes of Down Syndrome.
In 1992, working with Calvin Kuo, then a graduate student in his laboratory, he discovered that the immunosuppressive drug, rapamycin blocked a biochemical pathway leading to protein synthesis in response to membrane cell proliferation signals.
[13] This work contributed to the development of rapamycin as a therapeutic for certain human cancers and also played a role in the founding of Ariad Pharmaceuticals in Cambridge, Massachusetts.
His studies revealed that chemically induced proximity was a fundamental mechanism underlying many aspects of cellular signaling, including receptor activation ,[15][16] kinase function ,[17] protein localization ,[18] transcription[19] and epigenetic regulation .
Crabtree and colleagues Nathan Hathaway and Oli Bell have used induced proximity to make measurements of the dynamics of chromatin regulation in living cells leading to an understanding of the stability of epigenetic changes involved in cellular memory.
In the early 1990s Crabtree worked with Paul Khavari, now the Carl J. Herzog Professor of Medicine at Stanford University, to define the mammalian SWI/SNF or BAF complex by purifying and cloning the genes that encode its subunits.
[26][27] Using biochemical and genetic approaches he discovered that the genes that encode its subunits are put together like letters in a word to give a wide variety of different biological meanings.
The conclusion that the accumulation of these new mutations over the generations would lead to intellectual fragility was based on the estimate of the fraction of genes necessary for normal development of the nervous system, which is thought to be several thousand.