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
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. 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 (, 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, 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 by which homologous genomes come together and pair in the early embryo. (Joyce et al. 2012 PLoS Genetics, Joyce et al. 2013 PLoS Genetics, Senaratne et al. in preparation).

Genome visualization with Oligopaints: 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. (Beliveau, Joyce et al. 2012 PNAS, Beliveau et al. 2014 Curr Protocols Mol Biol, Murgha et al. 2015 Biotechniques, Pinter et al. 2015 Genetics, Beliveau et al. 2015 Nat Comm.)
HOPs, a strategy for distinguishing homologs: We have harnessed single nucleotide polymorphisms (SNPs) to enable a robust and reliable Oligopaint-based method for visually distinguishing the maternal and paternal homologous chromosomes in mammalian and insect systems. (Beliveau et al. 2015 Nat Comm.)
OligoSTORM and OligoDNA-PAINT, two single-molecule super-resolution strategies for visulaizing the genome: We have melded Oligopaints with two single-molecule super-resolution strategies to enable the fine-scale in situ analysis of chromatin structure. Here, we have used Stochastic Optical Reconstruction Microscopy (STORM, in collaboration with the laboratory of Xiaowei Zhuang) and DNA-based Point Accumulation in Nanoscale Topography (DNA-PAINT, in collaboration with the laboratories of Peng Yin and Ralf Jungmann). (Beliveau et al. 2015 Nat Comm.)

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. (Derti et al. 2006 Nat Gen, Chiang et al. 2008 Genetics, McCole et al. 2014 PLoS Genetics).

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 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).

Biomedicine in space: 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).

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.)

Last Update: 10/16/2015


For a complete listing of publications click here.



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.

McCole RB, Fonseka CY, Koren A, Wu C-t. Abnormal dosage of ultraconserved elements is highly disfavored in healthy cells but not cancer cells. PLoS Genetics 2014; 10:e1004646. PMCID: PMC4207606.

Pinter SF, Colognori D, Beliveau BJ, Sadreyev RI, Payer B, Yildirim E, Wu C-t, LeeJT. Allelic imbalance is a prevalent and tissue-specific feature of the mouse transcriptome. Genetics 2015 (in press).

Beliveau BJ, Boettiger AN, Avendaño MS, Jungmann R, McCole RB, Joyce EF, Kim-Kiselak C, Bantignies F, Fonseka CY, Erceg J, Hannan MA, Hoang HG, Colognori D, Lee JT, Shih WM, Yin P, Zhuang X, Wu C-t. Single-molecule super-resolution imaging of chromosomes and in situ haplotype visualization using Oligopaint FISH probes. Nat Commun 2015 (in press).

© 2015 by the President and Fellows of Harvard College