Far from Native China, Yunbo Liu Finds Focus in Ultrasound

Yunbo LiuWhen Yunbo Liu’s parents were growing up, most people in his native China -- his parents included -- did not go to college. Over the past 20 to 30 years, however, much has changed and the pursuit of a college education is now a popular option, said 27-year-old Liu, now in his fifth year as a graduate student in Mechanical Engineering and Materials Sciences at the Pratt School.

For him, there was never any doubt about a future in higher education. In his bustling home city of Tianjin – a place he likens to Boston because of its size, the weather, and the old streets and buildings -- when other high school kids were taking the Chinese equivalent of the SAT exam, Liu was exempted because his grades were already so good. He enrolled in Peking University and majored in mechanical engineering.

As an undergraduate, Liu spent two years studying the mechanical properties of composite materials, primarily through theoretical means and computer simulation. Although he admits that he initially pursued engineering based on the encouragement of others, in the process of his studies and research he began to realize his true interest: the application of his engineering talent to the biomedical field.

He also met his wife, Fan Chen, a fellow student at Peking University, and in 2001, the two found themselves bound for Durham, N.C., where Liu would join the MEMS department to research ultrasound technology in the lab of Pei Zhong. Duke, and Zhong’s lab in particular, offered him the perfect opportunity to blend his mechanical expertise with his enthusiasm for biomedical engineering, he said. His wife also enrolled as a graduate student at the University of North Carolina, Chapel Hill, where she studies geography.

Now, with just one more year of graduate school to go, Liu’s research is pushing the limits of ultrasound imaging into the realm of cancer gene therapy. First, they needed to develop focused ultrasound capable of penetrating tissue with acoustic vibrations concentrated at a very specific spot.

That focused energy can heat cancerous tissue, offering a non-invasive method, called high-intensity focused ultrasound or HIFU, to essentially cook a tumor to death from the outside, without affecting the surrounding area, Liu said. The method can raise the temperature of a section of tissue the size of a grain of rice up to 100 degrees Celsius in under 10 seconds. By comparison, the average human body temperature is 37 degrees Celsius.

“The approach offers a clean alternative to radiation,” Liu said. “Ultrasound, after all, is the imaging method used for pregnant women and babies. It’s really pure – just mechanical vibration.”

Their first target is breast cancer, Liu said. “The breast is a good target for ultrasound because it’s mainly soft tissue, in which acoustic waves penetrate well.”

The research team has tested their HIFU device on mice implanted with tumor cells. Within 10 to 20 days of implantation, the mice develop large masses which the team then attempts to treat with the ultrasound technology.

Related technologies are already in use, Liu said. The FDA approved a similar method last year for treating uterine fibroids and the approach has seen some use in Europe and Asia.

“HIFU has been approved to heat tumors directly, but you can’t kill all the cancer cells,” he said.

That dilemma led the Duke team to the most novel aspect of their research, Liu added. They are developing a method that combines focused ultrasound with gene therapy, to destroy cancer cells heated to sublethal temperatures.

The approach would take advantage of so-called heat shock proteins that switch on in response to stresses, including high temperature, to activate other genes that are toxic to cells or that stimulate an immune response as a way of eliminating persistent cancer cells, Liu said.

At the 5th International Symposium on Therapeutic Ultrasound held at Harvard Medical School in October, 2005, Liu presented some of the first evidence that such an approach might one day work in the fight against cancer.

Their high-intensity focused ultrasound device successfully activated a green fluorescent protein in the solid tumors of mice, he reported. Liu was selected as one of five winners in the student research competition at the symposium, for “Excellence and Soundness of Research Methods.”

“I was awarded the honor because of the uniqueness of our idea,” Liu said. “We were the first group to realize that sublethal temperatures in the range of 50 to 60 degrees C could be used to induce the expression of heat-sensitive genes in a few seconds.”

As for whether the non-invasive therapeutic ultrasound technique will ever make it to the clinic, Liu sounds confident. “It’s just a matter of time,” he said. After graduation, he plans to pursue the ultrasound technique at a research institute or in industry.

“I’m young,” he said. “There is plenty of opportunity to develop my work. I will go anywhere in the world that seems to be the best choice. Europe, for example, is quite good for this kind of technology.”

Despite his drive and determination to see their ultrasound therapy through, Liu is also prepared to apply his expertise to the next challenge that comes his way.

“As an engineer, my overall goal is to develop technology,” Liu said. “Maybe our ultrasound will work for cancer treatment in 10 years, maybe not. That depends on many things – the market, policy and medical insurance, for example. Our goal is to focus on the technology to make this device possible. It will be the doctors and policymakers who ultimately make the end decision about whether to use it.

“Today there is promise in ultrasound; tomorrow it might be lasers,” he added. “If so, I’ll go ahead and pursue that. No technology holds on forever.”