September 15, 2003

Advanced Technology Lab
To Foster Collaborative Research

A plan conceived several years ago to create a new applied biotechnology research center at UConn comes to fruition this week, with the dedication of the Advanced Technology Laboratory.

The two-story arc-shaped building houses laboratories and administrativ e offices of UConn's new Center for Regenerative Biology; the Technology Incubation Program, designed to jump-start high-technology business incubators in the state; and two of the teaching laboratories of the College of Agriculture and Natural Resources.

Professor Jerry Yang has assembled a new group of researchers in the field of regenerative biology, shown here with Provost John Petersen, second from right. The researchers are, from left, Joanne Conover, William Fodor, Cindy Tian, Yang, Theodore Rasmussen, and David Goldhamer. Photo by Dollie Harvey

It is connected by a walkway to the existing and similarly arc-shaped three-story Agricultural Biotechnology Laboratory, climate-controlled greenhouses and animal laboratory facilities. Collectively these buildings are known as the UConn BioScience Complex and represent another milestone in the transformation of the University's science facilities.

The project was the brainchild of Provost John D. Petersen and animal science professor Xiangzhong (Jerry) Yang, who wanted a center that would link Yang's expertise in animal science biotechnology with the powerful new possibilities opening up in the field of regenerative medicine.

The cutting-edge research done at the Center for Regenerative Biology, Petersen predicts, will help enhance UConn's growing national reputation.

"The way you build an institution's reputation for excellence is to pick and choose areas in which you can really excel," he says. "By investing in this new center, the University has capitalized on its longstanding strengths in animal science biotechnology, and moved forward into an area that has the potential to revolutionize the medical field."

Regenerative medicine has been made possible largely by new molecular techniques developed within the past few decades. Researchers are now able to study cells protein by protein. They can put new genes into a cell and take genes out, even design their own. They're learning to use the signals that tell our DNA what to do. And in the field of regenerative medicine, they are using this knowledge to learn to produce healthy new tissues and organs that can be transplanted into patients who have, through illness, age, or accident, lost their own.

In principle, regenerative medicine could offer cures - not just palliatives - for diseases such as Alzheimer's and Parkinson's, diabetes, or leukemia.

"It is an area that's at the forefront of biological research," says Janet Greger, vice provost for research and graduate education.

Although many colleges and universities are venturing into this field, UConn's new center is characterized by bringing together many different pieces in order to realize the possibilities.

At its core are five newly recruited professors, each working in a carefully chosen area that brings complementary expertise to UConn's existing, strong embryo biotechnology program. Yang, the center's director, says much of the group's research will focus on what's known as therapeutic cloning: taking DNA from, say, an animal's skin cell and, through a series of steps, coaxing that DNA to form whatever type of tissue is needed.

Yang is widely recognized for his breakthroughs in animal cloning. He was the first to determine how to use skin cells to clone mammals, a technique which led to the creation of the first male clones from a prize Japanese bull in 1998. Since then the technique has been widely adopted.

In another key discovery, Yang and his lab reported that somatic cells that had been cultured and stored for a long time could be used effectively for cloning. Currently the lab is focusing its research on de-differentiation of differentiated cells to viable stem cells, un-specialized cells that possess the ability to turn into a variety of different types.

Producing stem cells is just a first step. Yang's vision for the center's research group included a molecular embryologist - someone who understands how development occurs; a person working on cell differentiation, or what signals cause stem cells to turn into particular cell types; a molecular geneticist, to look at what genes are doing as stem cells change; a developmental biologist, to study what happens as animals grow; and a person who focuses on tissue engineering and transplantation.

"We are trying to create a team environment by bringing together researchers with a common interest, and complementary areas of research," explains Yang.

The five new faculty he recruited are:

William Fodor, who was previously senior director at Alexion Pharmaceuticals of Cheshire. He has developed the use of special cells that have been able to restore partial functioning in animals with damaged spinal cords. His collaborations with research biologists at Yale and Harvard universities in the field of neural cell transplantation have focused on the development of cells to repair axons in spinal cord injury and replace cellular loss in Parkinson's disease models, respectively.

Cindy Tian, who came to UConn in 1996 and joined the center's faculty last year, focuses primarily on gene reprogramming to increase the success rate of the cloning process, and on understanding the process of gene reprogramming by somatic nuclear transfer. High rates of developmental abnormality of somatic clones point to the fact that the nuclear reprogramming process is incomplete and imperfect at this time. Understanding the mechanisms regulating the reprogramming events could lead to technologies for targeted re-differentiation of cells for tissue regeneration.

David Goldhamer, from the University of Pennsylvania School of Medicine, studies the gene activation process that directs certain clumps of embryonic cells to become muscle tissue and is investigating why, in some people, muscle stem cells produce bone instead of muscle. Recent evidence indicates that additional types of stem cells also exist in skeletal muscle tissue, the identification of which is essential for understanding diseases of abnormal bone formation and for developing therapies for musculoskeletal diseases.

Also looking at aspects of cell differentiation is Joanne Conover, from the Jackson Laboratory in Maine. Conover works with neuronal stem cells, isolating the process that turns them into one kind of brain cell rather than another. She is looking specifically at dopamine-produ cing neurons that could be used to cure Parkinson's.

Theodore Rasmussen, from the Whitehead Institute for Biomedical Research at MIT, also studies differentiation, but from the point of view of the genes. He's looking at how a family of proteins known as chromatins regulates which genes turn on and which do not, during stem cell differentiation. He hopes to gain an understanding of the underlying mechanisms that direct stem cells to differentiate into desired cell types.

The Advanced Technology Laboratory was designed to encourage collaboration not only among the researchers in regenerative biology but beyond. The center shares space with the Technology Incubator Program, which is devoted to developing campus-based start-up companies.

Additionally while center faculty will be using molecular techniques to explore therapeutic cloning, researchers at the Agricultural Biotechnology Laboratory next door will be using similar techniques for a variety of agricultural applications.

"We're happy to have these three entities together," says Yang. "The more centers there are in this area, the more opportunities there are for collaborations."

The intellectual synergy that Yang hopes to foster is not limited to biotechnology. Each of the five new faculty members is academically affiliated with an academic department, including the departments of molecular and cell biology, physiology and neurobiology, and animal science, and each will be appointed as an adjunct faculty member at the Health Center.

The intent, says Provost Petersen, was "to engage the whole institution."

For the center's researchers, the goals are far-reaching. "If we are able to succeed in converting one type of tissue to another," says Tian, "it will become possible to treat patients with their own resources, and much of what's now common in medicine will become simply unnecessary. Hopefully, we as a group will make a difference in reaching that goal."