Abstract

The aim of the Misteli laboratory is to understand how genomes are organized in vivo and how the architectural organization of the genome contributes to its function in health and disease. To this end, we are employing cell biological and biochemical methods and we are developing advanced imaging methods to probe genome organization in living cells and tissues. In particular, we are taking advantage of high-throughput imaging approaches to map genome regions with high precision in a large number of samples allowing for systematic spatial mapping and implementation of screening approaches for discovery. We have also 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 human aging and the relationship between aging and cancer. We use the rare premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS) as a model system in these studies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010309-21
Application #
10014346
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
21
Fiscal Year
2019
Total Cost
Indirect Cost

  Institution

Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Serebryannyy, Leonid; Misteli, Tom (2018) Protein sequestration at the nuclear periphery as a potential regulatory mechanism in premature aging. J Cell Biol 217:21-37
Baranes-Bachar, Keren; Levy-Barda, Adva; Oehler, Judith et al. (2018) The Ubiquitin E3/E4 Ligase UBE4A Adjusts Protein Ubiquitylation and Accumulation at Sites of DNA Damage, Facilitating Double-Strand Break Repair. Mol Cell 69:866-878.e7
Padmanabhan, S; Misteli, T; DeVoe, D L (2017) Controlled droplet discretization and manipulation using membrane displacement traps. Lab Chip 17:3717-3724
Zane, Linda; Chapus, Fleur; Pegoraro, Gianluca et al. (2017) HiHiMap: single-cell quantitation of histones and histone posttranslational modifications across the cell cycle by high-throughput imaging. Mol Biol Cell 28:2290-2302
Kubben, Nard; Misteli, Tom (2017) Shared molecular and cellular mechanisms of premature ageing and ageing-associated diseases. Nat Rev Mol Cell Biol 18:595-609
DeBoy, Emily; Puttaraju, Madaiah; Jailwala, Parthav et al. (2017) Identification of novel RNA isoforms of LMNA. Nucleus 8:573-582
Larson, Daniel R; Misteli, Tom (2017) The genome-seeing it clearly now. Science 357:354-355
Shachar, Sigal; Misteli, Tom (2017) Causes and consequences of nuclear gene positioning. J Cell Sci 130:1501-1508
Finn, Elizabeth H; Pegoraro, Gianluca; Shachar, Sigal et al. (2017) Comparative analysis of 2D and 3D distance measurements to study spatial genome organization. Methods 123:47-55
Pegoraro, Gianluca; Misteli, Tom (2017) High-Throughput Imaging for the Discovery of Cellular Mechanisms of Disease. Trends Genet 33:604-615

Showing the most recent 10 out of 90 publications