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Haoyi Wang: The Big Projects

Haoyi Wang: The Big Projects
Postdoctoral associate, Jaenisch lab, Whitehead Institute, MIT
Recommended by Rudolf Jaenisch, Whitehead Institute, MIT

Wang2.jpgHaoyi Wang is interested in the big ideas.

Wang started his graduate career focusing on yeast transposons, in particular studying the Ty5 transposon. Around that same time another group worked out that that transposon interacts with Sir4, a regulatory protein.

Based on that, Wang and his colleagues developed a method dubbed 'calling card' that when combined with sequencing can mark where in the genome transcription factors bind. The approach works by fusing a bit of the Sir4 protein that interacts with Ty5 to the transcription factor of interest. The Ty5 transposon is then integrated into the genome near where that transcription factor binds. Additionally, each Ty5 transposon is barcoded to indicate with which transcription factor it was associated. Those calling cards can then be retrieved through sequencing.

"There's obviously multiplexing behind it because we know can leave a mark in the genome where you can barcode each experiment," Wang said. He added that he adapted the system for use in mammalian cells as well.

Then as he looked for a postdoc, he became interested in induced pluripotent stem cells as well as in TALEN and CRISPR-based genome editing. Recently, Wang has worked on developing a CRISPR-based system that can induce multiple genes as well as use TALENs to target certain genes in mouse embryonic stem cells to study the Y chromosome.

Wang is finishing up his postdoc, and plans to return to China as a junior faculty member. While starting his lab in China will have many advantages — such as a favorable funding climate — he noted that there would also be a number of challenges. Recruiting students and postdocs to his lab may be difficult, he said, especially as he works to establish the lab's name.

But he has a number of big ideas for the lab to pursue. In addition to continuing to work on genome engineering, Wang added that he is interested in working with big animals as well as studying sexual dimorphism. "I have to really prioritize my goals, depending on the resources I get," he noted.

Paper of note

Wang has published a number of articles, including one this year in Nature Biotechnology describing how he and his colleagues engineered TALENs to target the Y-linked genes Sry and Uty in mice. "We demonstrate that both Sry and Uty can be efficiently targeted by TALEN-mediated gene-editing strategies, enabling the genera¬tion of mice carrying Y-linked gene mutations," Wang and his colleagues wrote. "The system described … provides a novel and general approach for genetic manipulation of the Y chromosome, which has not been possible with conventional gene-targeting approaches."

And the Nobel goes to…

If Wang were to win the Nobel Prize, he'd like it to be for his work having a medical application. For instance, he noted that a number of patients with male infertility have Y chromosome mutations. If using genetic tools he could determine "what is causing those issues [and] really cure a lot of those patients, then it becomes a pretty important impact for society." At the same time, Wang added, such work could be coupled with gaining a better understanding of sexual dimorphism in behavior and disease.