The aim of our laboratory is to understand how genomes are organized in vivo and how this organization contributes to genome function in health and disease. We have made significant progress in several areas: We have extended our earlier efforts to develop imaging methods to visualize genome function in living cells. In particular, we have developed an experimental system which allows us for the first time to visualize the behavior of broken DNA regions in living cells. We have used this system to probe the mechanism by which cancer chromosome translocations occur in intact cells. We have also continued our ongoing work on exploring the spatial organization of the genome in the interphase cell nucleus. We have developed novel software tools to analyze spatial genome positioning and we have applied it to the analysis of genome organization differences in normal and cancer cells. We are applying these methods to the development of novel cancer diagnosis strategies. Finally, we are exploring the molecular mechanisms of the premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS), in particular as a means to uncover the process of aging-related tumor formation. We are exploring the mechanism by which higher order genome organization is lost in HGPS patient cells and we are investigating the molecular basis for the organismal defects in HGPS patients and during normal aging. We are also using HGPS to explore the molecular mechanisms of aging-associated cancer formation.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Investigator-Initiated Intramural Research Projects (ZIA)
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National Cancer Institute Division of Basic Sciences
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Dittmer, Travis A; Sahni, Nidhi; Kubben, Nard et al. (2014) Systematic identification of pathological lamin A interactors. Mol Biol Cell 25:1493-510
Roukos, Vassilis; Misteli, Tom (2014) The biogenesis of chromosome translocations. Nat Cell Biol 16:293-300
Burgess, Rebecca C; Burman, Bharat; Kruhlak, Michael J et al. (2014) Activation of DNA damage response signaling by condensed chromatin. Cell Rep 9:1703-17
Gordon, Leslie B; Rothman, Frank G; Lopez-Otin, Carlos et al. (2014) Progeria: a paradigm for translational medicine. Cell 156:400-7
Fernandez, Patricia; Scaffidi, Paola; Markert, Elke et al. (2014) Transformation resistance in a premature aging disorder identifies a tumor-protective function of BRD4. Cell Rep 9:248-60
Cavalli, Giacomo; Misteli, Tom (2013) Functional implications of genome topology. Nat Struct Mol Biol 20:290-9
Roukos, Vassilis; Burman, Bharat; Misteli, Tom (2013) The cellular etiology of chromosome translocations. Curr Opin Cell Biol 25:357-64
Misteli, Tom (2013) The cell biology of genomes: bringing the double helix to life. Cell 152:1209-12
Misteli, Tom (2009) Self-organization in the genome. Proc Natl Acad Sci U S A 106:6885-6
Mathas, Stephan; Kreher, Stephan; Meaburn, Karen J et al. (2009) Gene deregulation and spatial genome reorganization near breakpoints prior to formation of translocations in anaplastic large cell lymphoma. Proc Natl Acad Sci U S A 106:5831-6

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