Zhenhua Liu, nutrition, recently received a four-year, $499,000 grant from the U.S. Department of Agriculture’s National Institute of Food and Agriculture to study nutritional approaches to preventing obesity-related intestinal inflammation, which is believed to increase risk of colorectal cancer. The research team includes Richard Wood and Young-Cheul Kim of the nutrition department, Hang Xiao of food science and gastroenterologist Joel Mason of Tufts University.
Liu’s laboratory investigates how diet and lifestyle and their metabolically related gene variants interact in relation to chronic disease development. “There is inflammation in the intestine associated with obesity, some of which may lead to tumorigenesis,” Liu explains. “It can be a strong risk factor for colon cancer. But we do not know exactly how obesity contributes to this increased cancer risk.”
In previous studies, he had found that tumor necrosis factor-alpha (TNF-α), a cytotoxin that induces apoptosis or cell death, is elevated in the colons of obese mice. This elevation is associated with a genetic carcinogenic pathway known as Wnt. In his most recent work, Liu also has shown that genetically blocking the TNF-α pathway reduces pre-cancer indicators. This led him to propose testing the TNF-α pathway involving Wnt signaling experimentally in the mouse colon.
The researchers hope to determine whether inhibiting activation of TNF-α by dietary or genetic means can suppress the Wnt signaling pathway and reduce the rate of obesity-linked tumorigenesis. They plan a series of three studies in a genetically engineered mouse model and will use different doses of a combination of vitamin D and sulphoraphane, a molecule found in broccoli, to prevent inflammation in the gut compared to a control group, as well as studies using biochemical, molecular and functional genomics techniques.
“The ultimate goal of my laboratory is to integrate our biological findings with dietary and lifestyle strategies to diminish the burden of chronic diseases in our society,” says Liu. “If we find good results, we may be able to move on to human studies.”