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  September 17, 2001

Hla Studies Enzyme's Role in
Development of Cancerous Tumors

Things are looking pretty good for Timothy Hla from his lab on the fifth floor of the Health Center's Academic Research Building.

There's promise in his research on an enzyme that seems to cause cancer.

And there's promise in the Vascular Biology Center itself, which has grown dramatically under Hla's leadership.

"When I came to UConn Health Center in 1996, there was no focused effort in vascular biology, even though it was mentioned in the Health Center strategic plan," says Hla. "There were a couple of labs working on the vascular system but there wasn't much focused coordination and we didn't have much space."

Fast forward a few years and there's Hla as director of a Vascular Biology Center with an entire floor in a brand new research building, six principal investigators, and about 30 staff people.

Hla says the researchers recruited to join the department since his arrival have a variety of different scientific backgrounds: "We have specialists in RNA biochemistry, a field that looks at how genes are turned on and off in various cells; and we have specialists in the new field of proteomics, who were recruited to better define the protein changes that occur in various vascular diseases, using state-of-the-art technologies such as mass spectrometry ," says Hla. "All of us bring different skills and, even though we each have our individual projects, we work together on projects of common interests."

Hla's own research focuses on an enzyme, called Cox-2, and its role in the development of tumors, such as breast cancer. In a recent article in the Journal of Biological Chemistry, Hla and his colleagues reported that breast cancer developed spontaneously in mice by increasing the amounts of the Cox-2 enzyme.

His work also looks at the ability of non-steroidal anti-inflammatory drugs (NSAIDs), like aspirin, to suppress the activity of that enzyme and potentially prevent cancer. Because many risk factors for breast cancer, such as high fat diets and carcinogens, increase the level of Cox-2 in the breast tissues, this work suggests that the enzyme is important in tumor development.

Hla thinks excess amounts of Cox-2 interfere with the body's ability to destroy damaged cells. Cancer results when damaged cells multiply or mutate, rather than die.

"Cancer, though, is caused by a number of mutations, not just one," cautions Hla. "Our work looks at just part of the puzzle." More research is required to understand how Cox-2 works and how the aspirin-like drugs affect the enzyme. "Even if we knew for sure that the NSAIDs could suppress Cox-2, we'd need to know more about how to prescribe them, about dosages and possible side-effects of long-term use," he says. "Our work will continue to look for answers to some of those questions."

Cancer, however, is not the sole focus of the Vascular Biology Center. "The vascular system is in every organ. It's involved in many, many diseases besides cancer," says Hla. He points out that when blood vessels are blocked, for example, they cause heart disease. In diabetes, when blood vessels grow, they cause blindness. And in arthritis when vessels grow, they destroy joints.

"Our new Vascular Biology Center has a real advantage," says Hla. "Thanks to the design of the new research building, our laboratories are open, permitting people to move easily through them, and that helps scientific interactions. Through collaboration among our researchers with their distinct skills, we can begin to use multiple tools to attack a problem."

Kristina Goodnough

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