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Cholesterol expert Chang is named chair of biochemistry

"I'm a cholesterol biochemist wandering in the land of somatic cell genetics," says Ta Yuan Chang, Ph.D., when asked about his work. Yet if he'd made a different career choice in college, he might today be singing at the Taiwanese Opera House instead of serving as the newly appointed chair of biochemistry at Dartmouth Medical School.

Though he still occasionally treats colleagues and students to short performances of Chinese, Taiwanese, and English songs, Chang, who's been at DMS since 1976, does not regret dedicating his life to biochemistry. In both music and science, he says, "you have to be dedicated and enjoy what you're doing," but "it's easier to make a living as a scientist." And, he adds, there's "not so much travel!"

"T.Y." Chang—an expert in cholesterol metabolism and a member of the Dartmouth faculty since 1976—was recently named chair of the Department of Biochemistry.

Photo by Flying Squirrel Graphics

Cells: "T.Y." Chang began his scientific journey at the University of North Carolina at Chapel Hill, where he received his Ph.D. in biochemistry. He became interested in how cells regulate their cholesterol levels while working as a postdoctoral fellow with Dr. Roy Vagelos, first at Washington University and later at Merck Research Labs. There, he and colleagues started isolating what he calls "a unique weapon to solve cholesterol problems": mammalian somatic cells (any of a body's tissues or organs other than a sperm or egg, that is) with mutations that make them dependent on cholesterol for survival. Later, in his own lab at DMS, Chang and his team continued isolating cholesterol- requiring mutants and using them as tools to clone new genes involved in cholesterol metabolism.

Cathy Chang, his wife and long-time research associate, achieved the first cloning of ACAT, an enzyme that cells use to convert the cholesterol they acquire from the bloodstream into a storable form called cholesterol ester. (This work was described in a feature in the Spring 1995 issue of Dartmouth Medicine.) The buildup of cholesterol esters in various cells—in the liver, intestines, and blood vessels—can lead to hyperlipidemia and atherosclerosis.

Neuronal degeneration: Although atherosclerosis is the most notorious problem involving cholesterol, there are others, including Niemann-Pick type C disease (NPC). Patients with NPC die in early childhood due to progressive deterioration of the central nervous system. NPC-1, another of the cholesterol metabolism genes cloned with the help of the Chang lab's "unique weapon," is mutated in humans with NPC.

How does a problem in cholesterol metabolism result in degeneration of neurons? To answer this question, Chang enlisted the help of two members of the biochemistry faculty with expertise in neuronal development and function: Leslie Henderson, Ph.D., and Robert Maue, Ph.D. Using mice lacking the NPC gene as a model, these three researchers and their labs have started uncovering the events that may go awry in the brains of NPC patients.

Chang sees this sort of collaboration as a natural outcome of the scientific culture in DMS's biochemistry department: "This department demands that every PI [principal investigator] be very independent, but intellectually we're very close; the common denominator is scientific excellence. People pursue highquality research, and people respect scientific excellence."

Funding: Chang's predecessor as chair, William Wickner, M.D., led the department since 1993 to number-eight ranking among all biochemistry departments in the country for funding per faculty member. The department counts among its 16 faculty a member of the National Academy of Sciences and five recipients of prestigious MERIT Awards from the National Institutes of Health. Chang's goal is to build on Wickner's legacy and to increase those numbers over the next decade.

"How to do this?" he asked the biochemistry faculty recently. "[I] need everyone's input. I would like to emphasize that cohesiveness is our real strength." Continuing to build and strengthen relationships among the members of the department, as well as with faculty in other departments at DMS and at Dartmouth College, is another of Chang's priorities. He hopes biochemistry can hire two more faculty members this year, with expertise ranging from biochemistry and cell and molecular biology to structural biology. He's especially excited about the prospect of adding a structural biologist, since he sees that as a methodology currently lacking at DMS.

In his own lab, Chang plans to continue studying ACAT, NPC, and other players in cholesterol metabolism. New roles for ACAT—including the enzyme's possible involvement in gallstone formation—are being explored with help from ACATknockout mice. "We don't have to worry to find things to do before we retire," he says, laughing. "I think cholesterol research will go on forever."

Marta Hristova (email)

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