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Ting Wang: Transposable Elements, Regulatory Networks, and the Epigenome

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Title: Assistant professor, Washington University School of Medicine
Education: PhD, Washington University in St. Louis, 2006
Recommended by: Francis Collins, National Institutes of Health

While working toward his doctorate degree in computational biology at Washington University in St. Louis, Ting Wang disregarded repetitive elements when writing algorithms to screen for transcription factor binding sites. Then, as a postdoc in David Haussler's lab at the University of California, Santa Cruz, he made a surprising discovery: more than 30 percent of human p53 binding sites were the result of transposable elements. "Then, all of the sudden, my scientific career was about repeats," Wang says. He and his colleagues published this finding in a 2007 PNAS paper.

In his own lab at Washington University in St. Louis, Wang now seeks to understand how transposable elements have shaped regulatory networks and the human epigenomic landscape over time. Transposons, he says, have really come into their own as more and more labs have transitioned from microarray-based studies to next-gen sequencing projects. Still, many investigators "throw away most of the reads that cannot be uniquely aligned to the [reference] genome," Wang says.

He and his lab members are taking a multifaceted look at how transposable elements have contributed to human health and disease. "We are truly a joint wet-and-dry lab," Wang says. "We develop algorithms, we develop genome browsers, and we generate our own data."

Wang and his team have also taken a keen interest in understanding the role of transposable elements in epigenetic regulation, and in particular, DNA methylation. Using zebrafish models, the Wang lab is monitoring DNA methylation changes throughout embryogenesis to establish baseline reads. From there, "we want to know the [phenotypic] impact of manipulating transposon methylation," he says.

On the informatics end, Wang's team is developing a novel epigenome browser, which builds on the success of the UCSC model but includes additional, unique visualization capabilities. Conventional browsers allow users to examine on the order of 10 to 20 tracks of data at a time. Wang says that because "we're really dealing with hundreds of thousands of tracks in epigenomics data sets," his team has created genome heatmaps that allow users to "visualize hundreds of data sets on the same computer screen." In addition, the Wang group's browser includes an option to visualize the metadata that accompanies a given genome in a heatmap alongside the genomic visual. He expects to launch the epigenome browser by early 2011.

Papers of note

In a Nature Biotechnology paper published this September, Wang and colleagues including Joe Costello at the University of California, San Francisco, described sequencing-based methods for DNA methylation profiling and epigenetic modification identification.

And the Nobel goes to ...

According to Wang, the late Barbara McClintock "really deserves another Nobel Prize, just for saying [transposable elements] can regulate gene expression." He says that the majority of his research seeks to answer the questions that McClintock and others posed several decades ago, but "with different technologies" and on "a systems level." While he's reluctant to discuss winning a prize, Wang isn't hesitant about wanting to "challenge lots of the conventional wisdom about transposable elements."

"We want to make conceptual leaps, contributions to the way we think about biology," he says. One of those ways is by demonstrating that transposable elements, though they're not themselves functional, are in fact "functionally important," he adds.

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