Department of Defense funds tumor research

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John Carberry

A Cornell researcher seeks to understand the mechanism behind the abnormal protein synthesis from the inherited disease tuberous sclerosis or tuberous sclerosis complex (TSC), thanks to a two-year $100,000 Exploration -- Hypothesis Development Award from the Department of Defense (DOD).

Shu-Bing Qian, assistant professor of nutritional sciences in the College of Human Ecology, is working to uncover missing links in understanding why cells continue to synthesize proteins and grow due to mutated genes, called TSC1 and TSC2, in TS patients.

In people with TSC, benign tumors grow in many organs, but the condition can lead to severe epilepsy, mental retardation and autism when such tumors grow in the brain, and some tumors, particularly kidney and brain tumors, can become cancerous.

The research may not only lead to new drugs to treat TSC, but also provide clues to larger questions regarding the role of protein synthesis in such diseases as cancer.

"We are trying to answer why protein synthesis becomes uncontrolled when TSC genes are mutated in patients with tuberous sclerosis," said Qian.

In normal cells, TSC1 and TSC2 genes act as sensors for nutrients; when cells lack nutrients, the genes slow growth by signaling a regulator called TOR to stop synthesizing proteins. But when the genes are mutated, protein synthesis and growth continue even when nutrient levels are low, which leads to tumors. Qian plans to create ways to monitor protein synthesis accurately under a variety of scenarios to understand the steps between inactive nutrient sensing and uncontrolled growth. Once the "missing links" are determined, they may be the targets for drug therapies to curb the tumor growth, Qian said.

Also, Qian will experiment with a U.S. Food and Drug Administration-approved drug called rapamycin, a protein synthesis inhibitor, which targets TOR signaling. But, rapamycin does not inhibit all protein synthesis, and the reasons could lead to clues that relate to TSC, Qian said.

The award was funded by the DOD's Tuberous Sclerosis Complex Research Program of the Office of the Congressionally Directed Medical Research Programs.

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Krishna Ramanujan