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. 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.
| 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 |
| Misteli, Tom (2009) Self-organization in the genome. Proc Natl Acad Sci U S A 106:6885-6 |
| Mejat, Alexandre; Decostre, Valerie; Li, Juan et al. (2009) Lamin A/C-mediated neuromuscular junction defects in Emery-Dreifuss muscular dystrophy. J Cell Biol 184:31-44 |
| Pegoraro, Gianluca; Misteli, Tom (2009) The central role of chromatin maintenance in aging. Aging (Albany NY) 1:1017-22 |
| Hager, Gordon L; McNally, James G; Misteli, Tom (2009) Transcription dynamics. Mol Cell 35:741-53 |
| Soutoglou, Evi; Dorn, Jonas F; Sengupta, Kundan et al. (2007) Positional stability of single double-strand breaks in mammalian cells. Nat Cell Biol 9:675-82 |
| Trotman, Lloyd C; Wang, Xinjiang; Alimonti, Andrea et al. (2007) Ubiquitination regulates PTEN nuclear import and tumor suppression. Cell 128:141-56 |
| Soutoglou, Evi; Misteli, Tom (2007) Mobility and immobility of chromatin in transcription and genome stability. Curr Opin Genet Dev 17:435-42 |
| Meaburn, Karen J; Misteli, Tom; Soutoglou, Evi (2007) Spatial genome organization in the formation of chromosomal translocations. Semin Cancer Biol 17:80-90 |
| Kruhlak, Michael; Crouch, Elizabeth E; Orlov, Marika et al. (2007) The ATM repair pathway inhibits RNA polymerase I transcription in response to chromosome breaks. Nature 447:730-4 |
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