Epigenetics is the study of heritable changes in phenotype through a mechanism other than genetic sequence—e.g., DNA cytosine methylation, histone post-translational modifications, nucleosome positioning and chromatin organization. Epigenetic signatures differ between somatic cells and stem cells and between different tissue types, and are dysregulated in cancer. The epigenetic state has a strong effect on how genes are regulated, but the mechanism for this regulation is still being explored.
The Timp Lab is focused on two areas: parsing the biophysical mechanisms of epigenetics on a single molecule basis and dissecting how epigenetics affects and is affected by signal transduction on a single-cell basis via control of the cellular microenvironment. These two areas of research are synergistic; single molecule research is a bottom-up approach informing new targets to explore via FISH or immunofluorescence, or new signal pathways. The single-cell approach will reveal new epigenetic patterns, which researchers can then explore using the single molecule toolset.
Lab Website: Timp Lab
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Norris AL, Workman RE, Fan Y, Eshleman JR, Timp W. “Nanopore sequencing detects structural variants in cancer.” Cancer Biol Ther. 2016;17(3):246-53. doi: 10.1080/15384047.2016.1139236. Epub 2016 Jan 19
Timp W, Bravo HC, McDonald OG, Goggins M, Umbricht C, Zeiger M, Feinberg AP, Irizarry RA. “Large hypomethylated blocks as a universal defining epigenetic alteration in human solid tumors.” Genome Med. 2014 Aug 26;6(8):61. doi: 10.1186/s13073-014-0061-y. eCollection 2014
Kurz V, Nelson EM, Perry N, Timp W, Timp G. “Epigenetic memory emerging from integrated transcription bursts.” Biophys J. 2013 Sep 17;105(6):1526-32. doi: 10.1016/j.bpj.2013.08.010
Timp W, Feinberg AP. “Cancer as a dysregulated epigenome allowing cellular growth advantage at the expense of the host.” Nat Rev Cancer. 2013 Jul;13(7):497-510. doi: 10.1038/nrc3486. Epub 2013 Jun 13
Timp W, Comer J, Aksimentiev A. “DNA base-calling from a nanopore using a Viterbi algorithm.” Biophys J. 2012 May 16;102(10):L37-9. doi: 10.1016/j.bpj.2012.04.009. Epub 2012 May 15