Research in the Wu Laboratory |
Our laboratory studies how chromosome behavior and positioning influence genome function and evolution, with implications for gene regulation, genome stability, and diseases such as cancer and neurodevelopmental disorders. Using mammals, Drosophila, and nematodes and genetic, molecular biological, and computational tools, we approach these topics from a variety of angles. We also develop technologies for visualizing chromosomes, including Oligopaints, a strategy for fluorescent in situ hybridization (FISH) that has enabled homolog-specific FISH and in situ super-resolution microscopy of chromosomal DNA at a resolution of ≤ 20 nm. Most recently, we have begun developing projects addressing biomedical issues in space. Our laboratory is also the home for the Personal Genetics Education Project (pgEd.org), which accelerates public awareness of personal genetics. |
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Homolog pairing and sister chromatid cohesion in somatic cells
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Homolog pairing can influence gene expression through transvection, including the action of enhancers in trans. Using high-throughput FISH, we are conducting whole-genome screens for genes that control pairing. These studies have uncovered both pairing and anti-pairing activities, revealed a pairing-based signature that distinguishes the germ line from the soma early in embryogenesis, and brought us face-to-face with sister chromatid cohesion and the cell cycle. Most recently, we have begun applying Hi-C technologies to reveal the dynamic process of homolog pairing. (Joyce et al. 2012 Plos Genetics, Joyce et al. 2013 Plos Genetics, Senaratne et al. in preparation). |
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Polycomb group (PcG) genes |
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We have found that some genes of the PcG, which encode chromatin proteins, are important for pairing-associated phenotypes. Our work focusing on two such genes, Psc and Su(z)2, have identified several functional domains and provided evidence for intramolecular regulation. We are now exploring how Psc and Su(z)2 control gene expression both in vivo and in cell culture. (Emmons et al. 2009 Genetics, Nguyen et al. in preparation). |
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Biomedicine in space
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As part of the Consortium for Space Genetics (homepage), we are beginning to address issues of human health in space via two major lines of investigation. The first focuses on a strategy for combatting genome damage due to ionizing radiation. This effort stems from our study of UCEs (see above), which we predict hold a surprising potential to protect our genome from deleterious rearrangements. The second will explore the impact of extreme environments on chromatin structure. This effort will take advantage of our Oligopaint technologies, such as OligoSTORM and OligoDNA-PAINT, and examine the structure of the genome via in situ imaging of chromosomal DNA at ≤ 20 nm resolution (see above). |
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Other areas of interest |
The laboratory is also interested in gene regulatory and chromosomal mechanisms that can cause a diploid cell to be functionally hemizygous at specific chromosomal loci or across an entire chromosome. These include mechanisms such as random mononallelism, parental imprinting, X-inactivation, and loss-of-heterozygosity through mitotic recombination. (Wu and Dunlap 2002 Adv. Gen., Wu and Williams 2004 Genetics, Savova et al. in preparation.) |
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