Elizabeth Finn, Ph.D.

We study how the DNA in a cell’s nucleus is organized, to understand how cells make decisions.

The DNA in each of our cells, if stretched end to end, would be about three meters long. All of that DNA has to fold, wrap, and coil itself to fit inside the nucleus of each cell without getting tangled, which could be disastrous when a cell divides. But this folding process isn’t as simple as packing everything away neatly. Where the genes end up in a nucleus can affect how they work. A genome that is organized incorrectly can lead to cancer.

Previously, I used fluorescence imaging – highlighting individual genes with glowing chemicals – to map how chromosomes fold in different cells. I discovered each chromosome in each cell folds in a slightly different way. This means there are many “right” ways to organize a genome. I also noticed some interesting patters: certain shapes were more common in some cell types, and some parts of the genome showed more variation. This led me to think that variation itself might be an important part of how the genome functions.

My lab is exploring this idea in two ways. First, we are studying how the variation in genome organization changes during development and disease. And second, we’re working to understand how cells control the organization of their genomes.

The myriad different cell types in metazoans are a demonstration that a single genome can give rise to many different phenotypes. The processes of differentiation and the disorder found in diseases such as cancer and neurodegeneration show that individual cells can move fluidly from one state to another in response to environmental cues or genetic injury; this fluidity requires underlying variability. I found high levels of intrinsic variation in one important epigenetic feature, genome organization.

My lab is working to 1) identify the mechanistic sources of variability in genome organization, 2) measure and map it in developmental and disease models, and 3) clarify its molecular functional consequences.

Determine the mechanisms controlling variability in genome organization

A wide range of mechanisms have been shown to drive genome organization, most prominently a combination of three factors: loop extrusion by cohesin to anchors created by the chromatin architectural protein CTCF, chromatin compartments formed by self-association of heterochromatin, and the active reorganization driven by the cell cycle. Furthermore, many of these mechanisms -- along with genome organization -- are disordered in cancer. This leads to the hypothesis that genome organizational variability might be a global feature of cancer cells with many different etiologies. A mechanistic dissection of how the factors controlling genome architecture also contribute to plasticity and variability therein will yield insights into basic principles of how cells function. A more thorough understanding of how these mechanisms are altered in cancer may help us better understand that disease as well.

Investigating the cell-type specificity of variability in genome organization

Many studies have shown cell-type-specific genome organization on a population level. I observed in my own work that cell-type-specific associations can be marked by a change in mean distance or change in variability within the population. However, many of the mechanisms likely to affect variability in genome organization on a global level (such as length of the cell cycle, expression and targeting of chromatin factors, and overall transcriptional output) are cell-type-specific as well. I will thoroughly test the hypothesis that variability in genome organization is cell-type-specific using Hi-C and imaging in in vitro and in vivo models of development.

Determine the functional role of variability in genome organization

My ultimate goal is to determine how genome organization, and particularly variability therein, determines cellular functions. To directly address this question, it will be essential to specifically alter genome organization without inducing pleiotropic effects. A better understanding of the mechanisms controlling genome organization will present the tools necessary to do these studies, and a combination of in vitro and in vivo studies should shed light on this question.

Education

B.Sc., University of Chicago, 2004-2008
Ph.D., Stanford University, 2008-2014
Postdoctoral fellow, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 2015-2022

Honors and Awards

2010-2014 Stanford Graduate Fellowship in Science and Engineering (Smith Fellow)
2016, 2017 NIH Fellows Award for Research Excellence
2019 CCR Excellence in Postdoctoral Research Training Award

Joined OMRF scientific staff in 2022

View more publications

Recent Publications

Mian Y, Wang L, Keikhosravi A, Guo K, Misteli T, Arda HE, Finn EH. Cell type- and transcription-independent spatial proximity between enhancers and promoters. Mol Biol Cell:mbcE24020082, 2024 May, PMID: 38717453, PMCID: PMC11244156

Finn EH, Misteli T. Nuclear position modulates long-range chromatin interactions. PLoS Genet 18:e1010451, 2022 October, PMID: 36206323, PMCID: PMC9581366

Selected Publications

Nakayama, K., Shachar, S., Finn, E.H., Sato, H., Hirakawa, A., and Misteli, T. Large-scale mapping of positional changes of hypoxia-responsive genes upon activation. Mol Biol Cell. 2022. PMID: 35476603

Finn, E.H., and Misteli, T. A high-throughput DNA FISH protocol to visualize genome regions in human cells. STAR Protocols. 2(3):100741. 2021. PMID: 34458868, PMCID: PMC8377592.

Finn, E.H., and Misteli, T. Molecular basis and biological function of variability in spatial genome organization. Science. 365(6457):eaaw9498. 2019. PMID: 31488662, PMCID: PMC7421438.

Finn, E.H., Pegoraro, G., Brandão, H.B., Valton, A.L., Oomen, M., Mirny, L., Dekker, J., and Misteli, T. Extensive Heterogeneity and Intrinsic Variation in Spatial Genome Organization. Cell. 176(6):1502-1515. 2019. PMID: 30799036, PMCID: PMC6408223.

Finn, E.H., Pegoraro, G., Shachar, S., and Misteli, T. Comparative Analysis of 2D and 3D Distance Measurements to Study Spatial Genome Organization. Methods. 123:47-55. 2017. PMID: 28179124, PMCID: PMC5522766.

Finn, E.H., Smith, C.L., Rodriguez, J., Sidow, A., and Baker, J.C. Maternal Bias and Escape From X Chromosome Imprinting in the Midgestation Mouse Placenta. Dev Biol. 390(1): 80-92. 2014. PMID: 24594094, PMCID: PMC4045483.

Cell Cycle & Cancer Biology Research Program, MS 48
825 NE 13th Street
Oklahoma City, Oklahoma 73104

E-mail: Elizabeth-Finn@omrf.org

For media inquiries, please contact OMRF’s Office of Public Affairs at news@omrf.org.

Rachel McNamar, Ph.D.
Postdoctoral Scientist

Victoria "Meg" Butler
Research Technician I

Jase Daugherty
Administrative Assistant III

Denna Mills
Administrative Assistant II