Xu aims for grasp of cancer spread

When he started college in Shanghai, China in the 1970s, Tian Xu did not know what he wanted to do with his life. He had never even heard of the word “genetics.” But 30 years later, Xu, vice chairman of genetics at the School of Medicine, conducts cutting-edge research with fruit flies, worms and mice that seeks to understand what goes on in genes when cancer strikes.

Xu’s lab — which is funded by the Howard Hughes Medical Institute and is located in the Boyer Center for Molecular Medicine — aims to create technology to help scientists understand disease and human biology so that they can eventually create new medicines, he said.

Research currently underway in the lab includes work on cancer pathways and transposons — “mobile genetic elements” that can disrupt gene function — in mammals, Xu said.

Xu said his interest in genetic research initially stemmed from his desire to conquer human disease and help the sick.

“I grew up in China and we went through the Cultural Revolution,” he said. “I was young and I was once rejected for medical treatment there. So, with understanding biology and learning about the unknown, helping people is a really satisfying experience.”

Xu’s lab began this research by mutating the flies’ somatic cells to create tumors. This step led to the discovery of an important pathway for cancer growth involving Tuberous Sclerosis Complex — or TSC — genes, he said. Other scientists have confirmed this research in humans and have developed corresponding drugs for cancer patients.

Xu said his current focus is on metastasis — the spread of cancer — which is the main cause of mortality in patients. But he said understanding metastasis in mammals was not a simple task.

For years, Xu tried to discover metastasis’ mechanism to no avail and eventually looked to his students for input. Xu said he asked Raymond Pagliarini GRD ’04 to perform research on mammalian metastasis. Pagliarini came back two and a half years later with a successful modification on the fruit fly method.

With research in hand, the pair published a paper on these findings in “Science” magazine entitled “A Genetic Screen in Drosophila for Metastatic Behavior” in 2003.

Another mammal project the lab is currently working on is identifying gene function in mice through modified moth transposons. Xu and his lab have discovered genes that may suppress autoimmune response, alter pain response and even grow tusks, he said.

But despite the seriousness of his work, Xu said he tries to have fun with it.

When female mice consistently rejected a male after a certain gene was disrupted, Xu asked for suggestions for the gene’s name. While one student offered the name YoB (for “You Bastard!”), he said his favorite was the HNN gene, for “Honey, Not Now.”

Xu has a second lab at his alma mater, Fudan University in Shanghai. There, scientists perform the animal work, including breeding of the mutated species. He said he uses videoconferencing to communicate with the lab in China.

Graduate students and post-doctoral fellows working under Xu said they have enjoyed their lab experiences with him.

Thomas Ni GRD ’10, who joined the lab four years ago, said one of the reasons he has stayed so long is the pioneering projects.

“The projects of this lab are all very exciting, and they’re high risk, high reward,” he said.

Jonathan Cornett, a postdoctoral fellow, met Xu at a presentation held in Cornett’s school. Impressed with the work, he left his alma mater Emory University to join Xu at Yale about a year ago, he said.

“I was very impressed with what he was doing, and what he is doing right now,” Cornett said.

In the future, Xu said he hopes to continue his research in identifying disease genes and to one day receive funding to discover mammalian genes related to longevity and aging so that “people can live up to 500 years.”

His research has led to the creation of a new lab for continual research on identifying disease genes in the Yale West Campus, the former Bayer complex.

Comments