BBS Faculty Member - Chao-ting Wu

Chao-ting Wu

Department of Genetics

Harvard Medical School
New Research Building, Room 264
77 Avenue Louis Pasteur
Boston, MA 02115
Tel: 617-432-4431
Fax: 617-432-7663
Email: twu@genetics.med.harvard.edu
Lab Members: 4 postdoctoral fellows, 5 graduate students
Visit my lab page here.



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 (below). We also develop technologies for visualizing chromosomes, including strategies for fluorescent in situ hybridization (FISH) and super-resolution microscopy. 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.

Homolog pairing and sister chromatid cohesion in somatic cells: 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 and brought us face-to-face with sister chromatid cohesion and the cell cycle.

Polycomb group (PcG) genes: 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 do¬mains 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.

Ultraconserved elements (UCEs): The perfect conservation of UCEs between distantly related mammals has been a long-standing puzzle. Breaking from more popular models, we propose that UCEs maintain genome integrity via pairing and sequence comparison. We are testing this model using computational and wet bench strategies to reveal the relationship between UCEs and copy number variants (CNVs), selection pressure, and disease, such as cancer.

Biomedicine in space: We are beginning to address issues of human health in space, with a focus on strategies for combatting genome damage due to ionizing radiation.

Gene dosage: There are a number of 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. We are exploring these phenomena via computational and cytogenetic approaches.

Genome visualization: We develop technologies for visualizing chromosomes and revealing their organization within the nucleus. One such technology is Oligopaints, an oligo-based approach for FISH that can be used to image single copy regions as small as tens of kilobases and as large as tens of megabases. We are also exploring the use of super-resolution microscopy for the fine-scale analysis of chromatin structure.



Last Update: 6/18/2014



Publications

Wu C-t, Williams BR. Does random X-inactivation reflect random choice between two X chromosomes? Genetics 2004 167:1525-8 PMID: 15280260, PMCID: PMC1470940.

Derti A, Roth FP, Church GM, and Wu C-t†. Mammalian ultraconserved elements are strongly depleted among segmental duplications and copy number variants. Nat Genet. 2006 38:1216-20 PMID: 16998490.

Chiang CWK, Derti A, Schwartz D, Chou MF, Hirschhorn JN, Wu C-t. Ultraconserved elements: Analyses of dosage sensitivity, motifs, and boundaries. Genetics. 2008 180:2277-93. PMID: 18957701, PMCID: PMC2600958.

Emmons RB, Genetti H, Filandrinos S, Lokere J, Wu C-t. Molecular genetic analysis of Suppressor 2 of zeste identifies key functional domains. Genetics 2009; 182:999-1013. PMID: 19528329, PMCID: PMC2728886.

Joyce EF, Williams BR, Xie T, Wu C-t. Indentification of genes that promote or antagonize somatic homolog pairing using a high-throughput FISH-based screen. PLoS Genetics 2012; 8: e1002667. PMCID: PMC3349724.

Beliveau BJ, Joyce ER, Apostolopoulos N, Yilmaz F, Fonseka CY, McCole RB, Chang Y, Li JB, Senaratne TN, Williams BR, Rouillard J-M, Wu C-t. A versatile design and synthesis platform for visualizing genomes with Oligopaint FISH probes. Proc. Nat. Acad. Sci. USA 2012; 109:21301-6. PMID: 23236188; PMCID: PMC3535588.

Joyce ER, Apostolopoulos N, Beliveau BJ, Wu C-t. Germline progenitors escape the widespread phenomenon of homolog pairing during Drosophila development. PLoS Genetics 2013 9:e1004013. PMCID: PMC3868550.

Beliveau BJ, Apostolopoulos N, Wu C-t. Visualizing genomes with Oligopaint FISH probes. Curr Protocols Mol Biol 2014 14.23. PMID: 24510436 PMCID: PMC3928790.



© 2013 by the President and Fellows of Harvard College