Jerry Crabtree

The Crabtree Lab

We are interested in the role of epigenetic mechanisms in the development of the nervous system and also in cancer. We focus primarily on the role of an ATP-dependent chromatin remodeling complex called mSWI/SNF or BAF that is frequently mutated in cancer and neurodevelopmental diseases. We are also developing new techniques based on chemically induced proximity to explore and understand how these mechanisms relate to autism, speech disorders and intellectual disability.

Research

Understanding the Words of Chromatin Remodeling

We are exploring the role of chromatin regulation in verebrate development using genetic, proteomic and genomic approaches in mice.

Design of Small Molecule Regulators

A general problem in signal transduction and transcription is the mechanism by which signals of different intensities are converted to different cell fates.

Publications

Rewiring cancer drivers to activate apoptosis.
Gourisankar S, Krokhotin A, Ji W, Liu X, Chang CY, Kim SH, Li Z, Wenderski W, Simanauskaite JM, Yang H, Vogel H, Zhang T, Green MR, Gray NS, Crabtree GR. Nature. 2023 Aug;620(7973):417-425. doi: 10.1038/s41586-023-06348-2. Epub 2023 Jul 26. PMID: 37495688 Free PMC article.

The CD8+ T cell tolerance checkpoint triggers a distinct differentiation state defined by protein translation defects.
Van Der Byl W, Nüssing S, Peters TJ, Ahn A, Li H, Ledergor G, David E, Koh AS, Wagle MV, Deguit CDT, de Menezes MN, Travers A, Sampurno S, Ramsbottom KM, Li R, Kallies A, Beavis PA, Jungmann R, Bastings MMC, Belz GT, Goel S, Trapani JA, Crabtree GR, Chang HY, Amit I, Goodnow CC, Luciani F, Parish IA. Immunity. 2024 Jun 11;57(6):1324-1344.e8. doi: 10.1016/j.immuni.2024.04.026. Epub 2024 May 21. PMID: 38776918

PU.1 and BCL11B sequentially cooperate with RUNX1 to anchor mSWI/SNF to poise the T cell effector landscape.
Gamble N, Bradu A, Caldwell JA, McKeever J, Bolonduro O, Ermis E, Kaiser C, Kim Y, Parks B, Klemm S, Greenleaf WJ, Crabtree GR, Koh AS. Nat Immunol. 2024 May;25(5):860-872. doi: 10.1038/s41590-024-01807-y. Epub 2024 Apr 17. PMID: 38632339 Free PMC article.

Context-specific functions of chromatin remodellers in development and disease.
Gourisankar S, Krokhotin A, Wenderski W, Crabtree GR. Nat Rev Genet. 2024 May;25(5):340-361. doi: 10.1038/s41576-023-00666-x. Epub 2023 Nov 24. PMID: 38001317 Review.