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Contents - Winter 2009

Vol. 2 No. 1

Searching DNA for Answers to Cancer

Click here to watch a video of Wei Xiao discussing his work.

By Matt Barron

Like many children in China during the Cultural Revolution, Wei Xiao had no access to classes or books, except Chairman Mao’s infamous Red Book. Living in a Red Guard training camp with parents he rarely saw, the nine-year-old turned his enquiring mind to stamp collecting.

Xiao eventually earned a PhD in microbiology at the University of Saskatchewan (U of S) and a postdoctoral fellowship at Harvard, where he began to study something more elusive than the rarest of stamps: the mechanisms of DNA repair.

Driven by a lifelong curiosity and desire to unearth what others might miss, the U of S microbiologist has been teasing apart the mysteries of how cells repair damage to DNA. His landmark discoveries could lead to treatments for cancer and for such viral heavyweights as SARS and HIV.

It started 10 years ago with, of all things, a discovery in baker’s yeast. Xiao learned that he could make yeast cells more vulnerable to environmental threats by deleting a particular gene. After isolating two similar genes in humans, Xiao and his team discovered that, when either of these genes was placed in yeast cells containing the deleted gene, cell damage was prevented.

In 2005, he revealed the true nature of these “twin” genes—dubbed “Beauty” and “Beast.” Selected as a Milestone in Canadian Health Research, the research indicated that Beauty helps repair DNA, while Beast battles intruders by multiplying white blood cells and other immune players.

When it’s regulated properly, Beast complements Beauty by encouraging cell division. But when it isn’t, the Beast gene becomes a true beast. “Imagine if human cells were constantly multiplying without an infection,” says Xiao. “That is the hallmark of cancer.”

Xiao is currently experimenting with certain chemical agents and antibodies to halt this process. He hopes it will one day yield early-screening tools and better treatments for cancer.

Having isolated human genes responsible for DNA repair, Xiao recently turned to the plant kingdom with more questions.

In research led by doctoral student Rui Wen and involving U of S biochemist Hong Wang, the team identified for the first time a gene that helps plants resist environmental stress. The finding could lead to development of plants with superior abilities to tolerate UV light and other forms of radiation.

But early in 2008—around the same time he received the 2008 U of S Distinguished Researcher Award, which recognizes a faculty member’s contribution to scholarship—Xiao had a breakthrough.

In a study published in the prestigious journal Cell, and funded by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Council, the team hit upon the signal that prompts cells to battle such cancer-causing agents as X-rays and industrial toxins.

“With no exaggeration, this is the result that many in the field have awaited with anticipation for some 20 years,” said Michael Ellison, director of the Institute for the Biomolecular Design and Project CyberCell at the University of Alberta.

Scientists had known for many years about a protein complex called 9-1-1. It warns cells to halt the frenzied production of DNA-injured cells, a process that initiates cancer. But Xiao found a way to trigger—or dial—9-1-1.

Xiao, whose research has garnered the National Cancer Institute of Canada’s Research Scientists Award, has so far limited his attempts to dialing 9-1-1 in yeast cells. But the 9-1-1 response is also known to exist in human cells, and so Xiao will be exploring this capability in humans in the hope of providing another front on which to fight cancer.

While exploring DNA repair over the years, Xiao kept up the stamp collecting hobby that began in his youth. Years ago he wondered if there might be a stamp related to his discipline of experimental biology.

Xiao searched six volumes of world stamps, and hit upon an image of a European stamp featuring the genetic code table. To his surprise, he found the actual stamp one day at a Saskatoon dealer, and it has become one of the prizes of his collection.

The stamp lacks monetary value, Xiao says, “but it’s a joyful experience to find this stamp out of millions of stamps, to find this particular needle in the haystack.”