Research Professor of Pharmacology & Cancer Biology
Professor of Pediatrics
Duke University School of Medicine
Durham, NC 27710
The central focus of the lab is to understand how signaling pathway architecture and integration result in specific cell fates and how these properties have been hijacked in cancer cells. One approach relies on inducing defined pathway perturbations in epithelial cells to build a collection of prototypic signatures captured by microarray analyses, and use cell-based RNAi screens to identify effectors essential for the deployment of given signaling architectures highlighted by these gene signatures. Ultimately, our goal is to build an integrative understanding of the logic and structure in aberrant signaling network(s) known to drive tumor development and metastasis. A second effort deals with the extent to which cell-to-cell heterogeneity can affect the temporal dynamics and regulation of signaling pathways. We are focusing on the E2F/Rb network and have established a platform to follow in real time the activation and expression of E2F1 at the single cell level. In collaboration with the You lab (Duke Biomedical Engineering, and IGSP), which has developed mathematical approaches to model the behavior of the Rb/E2F network, we wish to identify functional characteristics in the signaling dynamics that may underlie disparate cell fates in response to a given external cue.
Dong P, Maddali MV, Srimani JK, Thélot F, Nevins JR, Mathey-Prevot B, You L. Division of labour between Myc and G1cyclins in cell cycle commitment and pace control. Nat. Commun. 5:4750 doi: 10.1038/ncomms5750 (2014).
Rämet M, Manfruelli P, Pearson A, Mathey-Prevot B, Ezekowitz RAB. Functional genomic analysis of phagocytosis and identification of a Drosophila receptor for Escherichia coli. Nature. 2002; 416:644-48
Kulkarni MM, Booker M, Silver SJ, Friedman A, Hong P, Perrimon N, Mathey-Prevot B. Evidence of off-target effects associated with long dsRNAs in Drosophila cell-based assays. Nat Methods, 2006; 3: 833-838.
Ramadan N, Flockhart I, Booker M, Perrimon N, Mathey-Prevot B. Design and implementation of high throughput RNAi screens in cultured Drosophila cells. Nat. Protocols, 2007; 2: 2245-2264
Gatza ML, Lucas J, Barry WT, Kim W, Wang Q, Crawford M, Ferguson E, Datto M, Kelley M, Mathey-Prevot B, Potti A, West M, Nevins JR. A Pathway-Based Classification of Human Breast Cancer. Proc Natl Acad Sci U S A. 2010; 107: 6994-9
Wong JV, Dong P, Mathey-Prevot B, You L. Network calisthenics: Control of E2F dynamics in cell cycle entry. Cell Cycle. 2011; 10: 3086-3094