Johns Hopkins Gazette: August 18, 1997

In Brief

Wagner named engineering dean at Case Western

James W. Wagner, a professor of materials science and engineering at Johns Hopkins, will become dean of the Case School of Engineering at Case Western Reserve University in Cleveland, effective Jan. 1, 1998.

Wagner joined the Hopkins faculty in 1984 and became a professor in 1993. He has been chairman of the Department of Materials Science and Engineering for the past four years. His research involves the use of laser-based technologies to evaluate the performance of materials without damaging them.

At the Case School of Engineering, founded in 1880, he will oversee undergraduate and graduate education programs in nine disciplines.

Medical News

Second look acquits gene of role in breast cancer

Johns Hopkins scientists studying a gene previously identified as a breast cancer gene report evidence that the gene may be innocent.

In a report in Cell last January, the TSG101 gene was identified as a tumor suppressor gene--a gene that is often mutated or damaged in human breast cancers.

In this month's Cancer Research, the Hopkins team says TSG101 was consistently normal and undamaged in human breast cancer cells. The cells could not correctly "read" TSG101, but researchers said the same mistake occurs in normal cells and is unlikely to help create cancer.

"This may be just another something the cancer cell messes up," says Andrew Feinberg. "It definitely does not appear to be contributing to cancer cells' creation, but since this is the first time we've observed such an error in a cancer cell's ability to decipher a gene, we're not sure yet if it provides any advantages to the cancer cell."

With funding from the Department of Defense, Feinberg and Maxwell Lee studied TSG101 in normal and cancerous human breast cells, and in other cells. They found no sign of deletions, mutations or other damage to TSG101 in any of the cells.

The cancer cells introduced mistakes into the gene's protein-building instructions, Feinberg says, but did so after "reading" the gene, which was not mutated.

"The cell encodes genetic instructions into a string of chemicals called ribonucleic acid or RNA, which later is used as a blueprint for building a protein," he explains. "But the string of RNA coding for the protein is normally interrupted at several points by coding that is not part of the protein. Before the cell can use it, it has to clip out these pieces. And it's in this 'splicing' process that something's going wrong in the cancerous cells."

In many cases, the cancerous cells cut too much out of the RNA, or incorrectly pasted together the remaining RNA. Normal and fetal cells made the same mistakes, but much less often.

"The earlier report of TSG101 deletions was actually detecting this altered splicing," Feinberg says.

"Is this important, this unusual splicing of RNA?" Feinberg asks. "It's possible. We think that a lot of what tumor cells do involves activating normal, specialized cell behaviors in an abnormal way, and this abnormal RNA splicing may be one example of that."

Where does the brain store physical skills, memories?

Researchers at Johns Hopkins and the University of Maryland have shown that people use one part of their brains to learn new physical skills, and store that memory within six hours in another part of the brain. The finding helps explain how skills as varied as tying a shoe and dancing on ice skates become automatic after a person learns how to do them.

The study also shows that the cerebellum, a lower part of the brain known to help control physical activity, is not involved in learning the skill. Instead, areas on the top and side of the brain learn the skill, which is then stored in the cerebellum.

"Our study supports the idea that the brain creates a blueprint, or model, for performing a particular task," says Reza Shadmehr, assistant professor of medicine and biomedical engineering at Johns Hopkins. "Once that blueprint is stored in the cerebellum, the brain uses it as a guide for controlling the movement of muscles used to perform that task."

The finding could help researchers learn how disruption of blood flow to the cerebellum because of drugs or injury affects the ability to remember how to perform physical tasks. This may help development of treatments that prevent the loss of physical skills, the scientists say. The study, co-authored by Henry H. Holcomb of the University of Maryland and the Department of Radiology at Hopkins, appears in the Aug. 8 issue of Science.

"We showed that when someone first masters a physical skill, their brain needs time to store the memory of how to perform that skill correctly," says Shadmehr. "This memory wasn't laid down in the cerebellum while volunteers practiced the skill in the lab. It occurred hours after the practice session had ended and the volunteers had left the room."

Using a positron emission tomography (PET) scanner to study changes in the blood flow in the brain, the researchers showed that, as volunteers learned a physical skill, there was increased blood flow in a part of the brain called the dorsolateral prefrontal cortex. This part of the brain is responsible for working memories, that is, memories that are regularly used, such as remembering how to prepare a favorite meal.

There was no increase in blood flow in the cerebellum during the learning process, or when volunteers performed only random physical tasks that they did not memorize. In both cases, increased brain activity as measured by blood flow was confined to the cortex.

But after the volunteers had mastered a skill, the increase in brain activity shifted from the cortex to the cerebellum during performance of the task.

"That is, the brain didn't have to use its higher centers of thinking to do the task, because performing the task became automatic," says Shadmehr.

The researchers studied the formation of memory in volunteers lying on their backs with their head in a PET scanner. The volunteers used a robot arm to place a pointer onto targets that appeared on a TV screen. The targets appeared in rapid succession in different areas of the screen, forcing the volunteers to learn how to move and control the robot arm quickly and effectively.

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