Increasing evidence indicates that cancer results not only from changes in genetic information;in the form of point mutations, chromosomal rearrangements, gene segment amplification and deletion, but also from changes in epigenetic information. Recent theoretical analyses of epigenetic regulation in a model organism (yeast) show that ideas from the dynamical systems field may explain the stability of epigenetic states and the dynamics of spontaneous changes between them. This project will experimentally define the epigenetic changes resulting from the action of (1) a mutant kinase JAK2V617F, a causative factor in myeloproliferative disease;(2) a defined set of oncogenes that transform normal human cells to cancer cells (T antigen, ras, shRNA PP2a, telomerase);and (3) the changes in state of the MLH1 promoter that accompany gene silencing associated with promoter methylation, and reactivation that is induced by 5-aza-2'-deoxycytidine and is associated with DNA demethylation. We will use this information to develop quantitative predictive models of epigenetic inheritance and switching in these systems, based on a dynamical systems framework.
| Serebryannyy, Leonid A; Yemelyanov, Alex; Gottardi, Cara J et al. (2017) Nuclear ?-catenin mediates the DNA damage response via ?-catenin and nuclear actin. J Cell Sci 130:1717-1729 |
| Shah, M Y; Martinez-Garcia, E; Phillip, J M et al. (2016) MMSET/WHSC1 enhances DNA damage repair leading to an increase in resistance to chemotherapeutic agents. Oncogene 35:5905-5915 |
| Voong, Lilien N; Xi, Liqun; Sebeson, Amy C et al. (2016) Insights into Nucleosome Organization in Mouse Embryonic Stem Cells through Chemical Mapping. Cell 167:1555-1570.e15 |
| Serebryannyy, Leonid A; Cruz, Christina M; de Lanerolle, Primal (2016) A Role for Nuclear Actin in HDAC 1 and 2 Regulation. Sci Rep 6:28460 |
| Hill, Steven M; Heiser, Laura M; Cokelaer, Thomas et al. (2016) Inferring causal molecular networks: empirical assessment through a community-based effort. Nat Methods 13:310-8 |
| Zhao, Baobing; Mei, Yang; Schipma, Matthew J et al. (2016) Nuclear Condensation during Mouse Erythropoiesis Requires Caspase-3-Mediated Nuclear Opening. Dev Cell 36:498-510 |
| Serebryannyy, Leonid A; Parilla, Megan; Annibale, Paolo et al. (2016) Persistent nuclear actin filaments inhibit transcription by RNA polymerase II. J Cell Sci 129:3412-25 |
| Chuang, Yishan; Hung, Michelle E; Cangelose, Brianne K et al. (2016) Regulation of the IL-10-driven macrophage phenotype under incoherent stimuli. Innate Immun 22:647-657 |
| Kreamer, Naomi N; Phillips, Rob; Newman, Dianne K et al. (2015) Predicting the impact of promoter variability on regulatory outputs. Sci Rep 5:18238 |
| Mulligan, Peter J; Chen, Yi-Ju; Phillips, Rob et al. (2015) Interplay of Protein Binding Interactions, DNA Mechanics, and Entropy in DNA Looping Kinetics. Biophys J 109:618-29 |
Showing the most recent 10 out of 161 publications
