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On the research fast track

The groundbreaking team of researchers at UConn's Center for Regenerative Biology includes, seated from left, Jerry Yang, Cindy Tian, Joanne Conover and David Goldhamer; standing: William Fodor, left, and Theodore Rasmussen.

The future of health care, agriculture and other scientific technologies is being invented at the University of Connecticut, working with science that could have been considered only futuristic fiction as recently as the 1980s. The dynamic force behind this revolution is a diminutive scientist who almost missed the biotechnology train that is currently racing down the tracks toward tomorrow.

UConn's new Advanced Technology Laboratory, a resource laboratory and research facility that was dedicated last fall, is a lifetime away from the rural village in China where Professor Xiangzhang "Jerry" Yang grew up. It could, in fact, serve as a counter symbol to the repression that nearly sidetracked Yang's career because without Yang's involvement, it might never have come to exist. Intellectual freedom is the very foundation of the Advanced Technology Laboratory. In almost every respect it is dedicated to the kind of research innovation that is rapidly transforming UConn's science facilities and revolutionizing the worlds of science and medicine.

The arc-shaped building is home to five research labs in the University's new Center for Regenerative Biology, which is led by Yang; two resource laboratories of the College of Agriculture and Natural Resources; and the Technology Incubation Program, which houses and nurtures emerging high technology businesses.

The seed for the Advanced Technology Laboratory was planted just seven years ago, shortly after Yang joined UConn as an associate professor of animal science and biotechnology and became head of the Biotechnology Center Transgenic Animal Facility. That Yang brought to UConn the expertise to launch such an endeavor is nearly miraculous, considering the circumstances under which he grew up.

As a young man, Yang was prevented from taking the entrance examination for the Beijing Agricultural University during the dark years of Mao Tse-tung's Cultural Revolution. It was only after Mao's death, in 1976, that Yang was able to take the test and enroll in the university's department of animal science.

Yang came to the United States in 1983 on a prestigious national fellowship and subsequently earned his master's and doctoral degrees at Cornell University. After completing his Ph.D., he became program director of Cornell's Department of Animal Science and assumed the task of creating an animal biotechnology program. It was in this role that he first became involved with the science of regenerative biology, or cloning.

It was, he says, the great mysteries of cellular science that engaged his fertile imagination. How, he wanted to know, do you reprogram genes to cure animal diseases and illnesses?

Yang began exploring that ponderous question with rabbit cells. By the late 1980s, he was working with cattle cells, considering the potential for the modification of genetic traits that could dramatically increase the productivity of dairy herds in countries like his native China. Soon he was on his way to UConn and a string of scientific breakthroughs that would establish his credentials as one of the world's leading experts on animal cloning.

The same year Yang arrived at UConn, a team of Scottish scientists produced the sheep Dolly, the first mammal to be cloned with DNA taken from an adult animal. Two years later, Yang had his own breakthrough, becoming the first scientist in the world to use skin cells to clone mammals. That scientific advance, now widely adopted, led to creation of male clones from a prize Japanese bull. A year later, Yang produced the first animal cloned from an adult farm animal in the United States. She was Amy, a calf, the vanguard of an animal cloning and transgenic technology program that is dramatically reshaping science, not only at UConn but also worldwide. As a result of Yang's work, just four years later, there are thousands of cloned farm animals around the globe.

In 2001, when he was named founding director of the Center for Regenerative Biology, it was clear that UConn was leaping, headfirst, into the rapidly expanding field of regenerative biology and medicine. "The way you build an institution's reputation for excellence is to choose and support areas in which you can really excel," notes Provost John D. Petersen, who worked with Yang and Kirklyn Kerr, dean of the College of Agriculture and Natural Resources, on the development of the Advanced Technology Lab.

"By investing in this new center, the University has capitalized on its longstanding strengths in animal science biotechnology and moved into an area that has the potential to revolutionize the medical field."

Photo: Peter Morenus

Researchers manipulate oocytes - eggs before maturation - at Jerry Yang's lab in the Advanced Technology Laboratory.

The Center for Regenerative Biology targets the enormous potential for the therapeutic production of new cells, tissues and organs that has been made possible, only in the last few years, by advances like those that have come from Yang's laboratories. To staff the new center, Yang worked with UConn officials to recruit a world-class team of scientists. William Fodor, previously senior director at Alexion Pharmaceuticals, has pioneered the use of special cells that restore partial functioning in animals with spinal cord injuries. David Goldhamer, who arrived from the University of Pennsylvania School of Medicine, studies how genes direct certain clumps of embryonic cells to become muscles and why this process develops musculoskeletal problems in some people. The work of Xiuchun "Cindy" Tian explores gene reprogramming to maximize cloning success. Joanne Conover, formerly of the Jackson Laboratory, researches neuronal stem cells and looks for neurons that could be used to cure Parkinson's Disease. Theodore Rasmussen, who came from MIT's Whitehead Institute for Biomedical Research, is studying how a group of cellular proteins called chromatins regulate which genes switch during stem cell differentiation, the time when the cells take their adult form and function.

Yang's dynamic team is not the only potential source of scientific innovation in the Advanced Technology Laboratory. UConn's new Technology Incubation Program (TIP) aims to use the University's considerable resources to help qualified entrepreneurial technology companies quickly advance.

If occupancy is a measure of success, then TIP is well on its way to the marketplace. TIP has five laboratories in the new building and three more at the UConn Health Center. All were filled almost from the day they became available.

There also is a long list of young companies waiting for the current occupants to become successful and vacate the laboratories. "Many people are anxious for an opportunity to work with Jerry Yang and his team," says Ian Hart, associate dean of research at the College of Agriculture and Natural Resources. It was precisely for this reason that the Advanced Technology Laboratory was designed, architecturally, to encourage collaboration. It is one of the hallmarks of intellectual freedom, a concept that Jerry Yang celebrates every day.

With an investment of resources from UConn, the young companies occupying incubator space in the Advanced Technology Laboratory and at the UConn Health Center are on a fast track to develop innovative products that will advance health science and improve quality of life. At the same time, entrepreneurial researchers bring their products to the market quicker. And UConn recoups its investment as the companies succeed. It might be called a win-win-win situation.

The work of Hepaticus, one of the Health Center incubators, is based on solving a problem that plagues liver disease researchers.

"Human liver cells are quite special," explains George Wu, a UConn professor of medicine who consults with Hepaticus. "Some agents that result in damage to human liver are very specific for primate tissue."

There has been no normal and commonly used laboratory animal with liver cells similar to human liver cells. Researchers have had to test new drugs on rats or mice, whose liver cells are quite different from human. Now that's about to change. Hepaticus' researchers have discovered a way to introduce human liver cells into fetal rats with normal immune systems. The result - rodents whose livers function like a human's - will almost certainly revolutionize liver disease research.

Incorporated last year, and led by their CEO, Carolyn Kahn, Hepaticus has been a UConn incubator since last fall and has established a partnership with the pharmaceutical company Boehringer-Ingelheim. With UConn assistance and collaboration with Boehringer-Ingelheim, the company expects to introduce its model rodents within the next two years.

Being a UConn incubator company, says Wu, has been "critical" to Hepaticus' success. "It means not only significant cost savings, but also access to technologies and assistance that can help a young company advance quickly," he says.