Donna D. Zhang, of University of Arizona Health Sciences, has received an eight-year, $7.3 million grant from the National Institute of Environmental Health Sciences to determine how a family of proteins can be harnessed to prevent or treat arsenic-induced lung cancer and Type 2 diabetes.
Zhang is the Musil Family Endowed Chair in Drug Discovery at the UArizona College of Pharmacy, research member at the UArizona Cancer Center, and associate director of the UArizona Superfund Research Center.
Arsenic is present in almost all groundwater sources in Arizona, particularly in rural areas. Combined with occupational exposures, such as mining, more than 160 million people worldwide have been exposed to potentially unsafe levels of arsenic.
Zhang began studying NRF2 in 2000 as a research assistant professor at the University of Missouri-Columbia, and has continued her work since joining UArizona Health Sciences in 2005.
“Three types of cancer primarily are induced by exposure to arsenic: lung, skin and bladder,” Zhang said in a statement. “This project will focus on lung cancer, and our goal is to identify new pharmaceuticals to prevent or treat adverse health effects resulting from arsenic exposure.”
Zhang’s past research has uncovered both positive and negative effects of NRF2, a protein that plays a critical role in protecting healthy cells because of its ability to control how certain genes are expressed in response to stressors. These genes help protect the cell from damage that can lead to cancer progression and resistance to therapy. NRF2 has been a therapeutic target for chemoprevention drugs to help slow or stop the spread of cancer and other diseases.
Zhang also has uncovered what she calls a “dark side” to NRF2. Although NRF2 has the positive benefit of protecting healthy cells, it also can protect cancer cells. This occurs when NRF2 is activated constantly, meaning it is not being properly regulated. The result of this hyperactivation can lead to cancer growth, spread and resistance to therapy. It also can promote a pro-diabetic shift in metabolism, which can lead to Type 2 diabetes.
“We are trying to better understand how arsenic disrupts the NRF2-mediated balance, resulting in lung cancer and Type 2 diabetes,” Zhang said. “We want to rationally target NRF2 with a rigorous, multitiered approach to generate legitimate therapeutic options to mitigate these diseases.”
