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Diana Hargreaves

Research

Our lab is interested in epigenetic regulation mediated by the BAF chromatin remodeling complex. Chromatin remodeling complexes are known to create DNA accessibility through hydrolysis of ATP to allow binding of transcription and repair factors to DNA. However, these large multi-subunit complexes also contain many other proteins of unknown function that are critical for development and highly mutated in human disease. Our goal is to use a combination of biochemical and epigenomic assays to understand the function of these complexes during normal cellular differentiation and the mechanistic basis for diseases caused by mutations in BAF complex subunits. We are focusing on cellular models of inflammation, cancer, and pluripotency.

Select Publications

  • Wang, L., Oh, T.G., Magida, J., Estepa, G., Obayomi, S.M.B., Chong, L-W., Gatchalian, J., Yu, R.T., Atkins, A.R., Hargreaves, D., Downes, M., Wei, Z., Evans, R.M. (2021) Bromodomain containing 9 (BRD9) regulates macrophage inflammatory responses by potentiating glucocorticoid receptor activity. PNAS, 118(35):e2109517118.
  • Loo, C-S*, Gatchalian, J.*, Liang, Y., Leblanc, M., Xie, M., Ho, J., Venkatraghavan, B., Hargreaves, D.C.#, Zheng, Y.# (2020) A genome-wide CRISPR screen reveals a role for the BRD9-containing non-canonical BAF complex in regulatory T cells. Immunity, 53(1): 143–157.e8. #co-corresponding authors *equal contribution.
  • Cortez, J.T.*, Montauti, E.*, Shifrut, E., Gatchalian, J., Zhang, Y., Shaked, O., Xu, Y., Roth, T.L., Simeonov, D.R., Zhang, Y., Chen, S., Li, Z., Woo, J.M., Ho, J., Vogel, I.A., Prator, G.Y., Zhang, B., Lee, Y., Sun, Z., Ifergan, I., Van Gool, F., Hargreaves, D.C., Bluestone, J.A., Marson, A.#, Fang, D.# (2020) CRISPR Screen in Regulatory T Cells Reveals Ubiquitination Modulators of Foxp3. Nature, 582:416–420.
  • Gao, F., Elliott, N.J., Ho, J., Sharp, A., Shokhirev, M.N., Hargreaves, D.C. (2019) Heterozygous mutations in SMARCA2 reprogram the enhancer landscape by global retargeting of SMARCA4. Molecular Cell, 75(5):891-904.e7. (Featured on the cover)
  • Gatchalian, J., Malik, S., Ho, J., Kelso, T.W.R., Shokhirev, M.N., Hargreaves, D.C. (2018) A non-canonical BRD9-containing BAF chromatin remodeling complex regulates naïve pluripotency in mouse embryonic stem cells. Nat Communications. 9(1):5139.
  • Kelso, T.W.R., Porter, D.K., Amaral, M.L., Shokhirev, M.N., Benner, C., Hargreaves, D.C. (2017) Chromatin accessibility underlies synthetic lethality of SWI/SNF subunits in ARID1A-mutant cancers. eLife . 6:e30506.
  • Miller, E.L. Hargreaves, D.C., Kadoch, C., Chang, C-Y., Calarco, J.P., Hodges, C.H., Buenrostro, J.D., Cui, K., Greenleaf, W.J., Zhao, K., Crabtree, G.R. (2017) TOP2 synergizes with BAF chromatin remodeling for both resolution and formation of facultative heterochromatin. Nature Structural and Molecular Biology. Nat Struct Mol Biol. 24(4):344-352.
  • Kadoch, C.*, Hargreaves, D.C.*, Hodges, C., Elias, L., Ho, L., Ranish, J., Crabtree, G.R. (2013) Proteomic and Bioinformatic Analysis of mSWI/SNF (BAF) Complexes Reveals Extensive Roles in Human Malignancy. Nature Genetics. 45(6), 592-601. *equal contribution
  • Dykhuizen, E.C.*, Hargreaves, D.C.*, Miller, E., Cui, K., Korshunov, A., Kool, M., Pfister, S., Cho, Y-J., Zhao, K., Crabtree, G.R Crabtree, G.R. (2013) BAF (mSWI/SNF) Complexes Cooperate with Topoisomerase IIa to Decatenate DNA. Nature. 497(7451), 624-627. *equal contribution
  • Hargreaves, D.C., Horng, T., Medzhitov, R. (2009) Control of inducible gene expression by signal-dependent transcriptional elongation. Cell.138(1), 129-145.
  • Foster, S.L.*, Hargreaves, D.C.*, Medzhitov, R. (2007) Gene-specific control of inflammation by TLR-induced chromatin modifications. Nature. 447(7147), 972-8. * equal contribution
  • Luther, S., Bidgol, A.*, Hargreaves, D.C.*, Schmidt, A., Xu, Y., Paniyadi, J., Matloubian, M., Cyster, J.G. (2002) Differing activities of homeostatic chemokines CCL19, CCL21, and CXCL12 in lymphocyte and dendritic cell recruitment and lymphoid neogenesis. J. Immunol. 169(1), 424-33. *equal contribution
  • Hargreaves, D.C.*, Hyman P.L.*, Lu, T.T., Ngo, V.N., Bidgol, A., Suzuki, G., Zou, Y., Littman, D.R., Cyster, J.G. (2001) A coordinated change in chemokine responsiveness guides plasma cell movements. J. Exp. Med. 194(1), 45-56. *equal contribution

Biography

Diana Hargreaves received her Ph.D. in Immunobiology from Yale University working under Dr. Ruslan Medzhitov and was a postdoctoral with Dr. Gerald Crabtree at Stanford University. She joined the Salk Institute in 2015, where she is currently an Associate Professor in the Molecular and Cell Biology Laboratory and holder the Richard Heyman and Anne Daigle Endowed Developmental Chair. She is the recipient of the American Cancer Society Research Scholar Award, the Pew-Stewart Scholar for Cancer Research Award, and the V Foundation Scholar Award and is an HHMI-Gilliam mentor.

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