Our laboratory studies tumor-suppressor networks controlling apoptosis and senescence and how their disruption influences malignant behavior.
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Cancer arises through an evolutionary process in which normal cells acquire mutations that erode growth controls, leading to the expansion of aberrantly proliferating cells. Such mutations activate oncogenes or inactivate tumor suppressors, bestowing new capabilities to developing cancer cells. Our research is based on the premise that the path of cancer evolution dictates a tumor’s subsequent response to therapy and creates unique vulnerabilities that represent therapeutic opportunities.
We use mouse models, RNA interference (RNAi), and cancer genomics to identify components of tumor suppressor gene networks and understand the molecular determinants of treatment response. We also use temporally regulatable RNAi technology to identify genes required for tumor maintenance and to explore the mechanisms involved in tumor regression, including both cell intrinsic and extrinsic mechanisms.
Our goal is to gain a more comprehensive understanding of tumor suppressor networks and identify cancer maintenance genes that will be useful therapeutic targets relevant to specific cancer genotypes.
Lujambio A, Akkari L, Simon J, Grace D, Bolden JE, Zhao Z, Thapar V, Joyce J, Krizhanovsky V, Lowe SW (2013). Non-cell-autonomous tumor suppression by p53. Cell. 2013 Apr 11;153(2):449-60. doi: 10.1016/j.cell.2013.03.020. Epub 2013 Apr 4.
Aksoy O, Chicas A, Zeng T, Zhao Z, McCurrach M, Wang X, Lowe SW. The atypical E2F family member E2F7 couples the p53 and Rb pathways during cellular senescence. Genes Dev. 2012 Jul 15;26(14):1546-57. doi: 10.1101/gad.196238.112.
Scuoppo C, Miething C, Lindqvist L, Reyes J, Ruse C, Appelmann I, Yoon S, Krasnitz A, Teruya-Feldstein J, Pappin D, Pelletier J, Lowe SW. A tumor suppressor network relying on the polyamine-hypusine axis. Nature. 2012 Jul 12;487(7406):244-8. doi: 10.1038/nature11126.
Zuber J, Shi J, Wang E, Rappaport AR, Herrmann H, Sison EA, Magoon D, Qi J, Blatt K, Wunderlich M, Taylor MJ, Johns C, Chicas A, Mulloy JC, Kogan SC, Brown P, Valent P, Bradner JE, Lowe, SW, Vakoc CR. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature. 2011 Aug 3;478(7370):524-8. doi: 10.1038/nature10334.
Premsrirut PK, Dow LE, Kim YK, Malone CD, Scuoppo Cl, Zuber J, Miething C, Dickins RA, Hannon GJ, Lowe SW. A rapid and scalable system for studying gene function in mice using conditional RNA interference. A rapid and scalable system for studying gene function in mice using conditional RNA interference. Cell. 2011 Apr 1;145(1):145-58. doi: 10.1016/j.cell.2011.03.012.
Biologist Scott W. Lowe is an expert on the processes that naturally inhibit cancer development.