Unlocking the mysteries of the liver
Photo by Markie RamirezWendong Huang links liver regrowth to cancer.
That can be important to survival, but Wendong Huang, Ph.D., assistant professor in the Division of Gene Regulation and Drug Discovery, also believes this trait might lie at the core of liver cancer.
The liver, which rests just under the diaphragm and next to the stomach, plays a major role in breaking down toxins and metabolizing many nutrients. It produces bile acids, which help the body absorb fatty acids and some vitamins in the small intestine.
If the liver is damaged, even severely, it can heal itself. Even with as little as 30 percent of its original mass remaining, the liver can regrow to full size. And no one knows how.
Huang recently received a $50,000 grant from the Concern Foundation to study how the liver repairs itself and how that ability is linked to liver cancer. He believes one of the key players could be a protein called farnesoid X receptor, or FXR.
FXR belongs to a class of proteins called nuclear hormone receptors. These proteins interact with hormones and act as switches to turn genes on and off.
FXR controls genes that regulate the amount of bile acids produced by the liver. Too much bile acid can be toxic, so if bile acid levels are high, FXR kicks in, setting a process in motion to lower them.
His earlier research prompts Huang to believe that bile acid regulation is directly linked to liver regrowth.
If bile acid levels get too high, FXR turns on genes that break down the acids, he said. But injury can leave the liver without enough of the FXR-controlled machinery it needs to balance bile acid levels. When that happens, FXR takes a second step: It stimulates the liver to regrow, which then gives it enough power to finish deactivating the acids.
Huang also has found a connection between FXR and liver cancer. In his research, lab mice that could not make FXR always develop liver tumors after about a year. He believes liver cancer and the liver’s unique ability to regenerate following injury are rooted in the same process.
“If the cycle of tissue damage and repair gets out of control or repeats too often, it can lead to permanent damage and even cancer,” he said.
Now Huang wants to delve deeper into this mystery to understand exactly how FXR stimulates liver regrowth and how that is connected to cancer in humans.
Funding from the Concern Foundation for cancer research will boost his work. Founded in Los Angeles in 1968, the Concern Foundation has raised more than $40 million to cultivate the expertise of outstanding young investigators and sustain the progress in prevention and treatment of cancer. Since its inception, Concern has awarded more than 500 “CONquer canCER Now” grants, and this year the organization is supporting an additional 50 researchers across the nation and world.
Huang believes the research could find much-needed answers. “This could help not just liver cancer patients, but patients with other cancer, as well,” he said. “If we can understand this, it could help a lot of people.”
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