We demonstrate a targeted approach to selectively eliminate TP53 mutant cancer cells by exploiting the increased abundance of mutant p53 protein, using an induced proximity strategy to concentrate a toxic molecule specifically within these cells.
We engineered bifunctional compounds that induce nuclear import of cytosolic proteins by using nuclear-localized BRD4 as a carrier. This paper helped to seed the field of “Targeted Protein Relocalization” and the sorts of compounds in it may one day be useful for treating diseases ranging from cancer to neurodegenerative disease.
Selected Pre-2023:
Loss of heterozygosity of essential genes represents a widespread class of potential cancer vulnerabilities.
Nichols CA, Gibson WJ, Brown MS, Kosmicki JA, Busanovich JP, Wei H, Urbanski LM, Curimjee N, Berger AC, Gao GF, Cherniack AD, Dhe-Paganon S, Paolella BR, Beroukhim R.Nat Commun. 2020 May 20;11(1):2517.
pubmed; journal; pdf
Copy-number and gene dependency analysis reveals partial copy loss of wild-type SF3B1 as a novel cancer vulnerability.
Paolella BR, Gibson WJ, Urbanski LM, Alberta JA, Zack TI, Bandopadhayay P, Nichols CA, Agarwalla PK, Brown MS, Lamothe R, Yu Y, Choi PS, Obeng EA, Heckl D, Wei G, Wang B, Tsherniak A, Vazquez F, Weir BA, Root DE, Cowley GS, Buhrlage SJ, Stiles CD, Ebert BL, Hahn WC, Reed R, Beroukhim R.Elife. 2017 Feb 8;6:e23268.
pubmed; journal; pdf
Genomic Heterogeneity and Exceptional Response to Dual Pathway Inhibition in Anaplastic Thyroid Cancer.
Gibson WJ, Ruan DT, Paulson VA, Barletta JA, Hanna GJ, Kraft S, Calles A, Nehs MA, Moore FD Jr, Taylor-Weiner A, Wala JA, Zack TI, Lee TC, Fennessy FM, Alexander EK, Thomas T, Janne PA, Garraway LA, Carter SL, Beroukhim R, Lorch JH, Van Allen EM.Clin Cancer Res. 2017 May 1;23(9):2367-2373.
pubmed; journal; pdf
The genomic landscape and evolution of endometrial carcinoma progression and abdominopelvic metastasis.
Gibson WJ, Hoivik EA, Halle MK, Taylor-Weiner A, Cherniack AD, Berg A, Holst F, Zack TI, Werner HM, Staby KM, Rosenberg M, Stefansson IM, Kusonmano K, Chevalier A, Mauland KK, Trovik J, Krakstad C, Giannakis M, Hodis E, Woie K, Bjorge L, Vintermyr OK, Wala JA, Lawrence MS, Getz G, Carter SL, Beroukhim R, Salvesen HB.Nat Genet. 2016 Aug;48
pubmed; journal; pdf
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