$7.3M Grant Advances UArizona Health Sciences Researcher’s Pursuit of Treatments for Arsenic-Induced Lung Cancer, Type 2 Diabetes

A University of Arizona Health Sciences researcher has been awarded an eight-year, $7.3 million federal grant to advance her two decades of research to determine how a family of proteins can be harnessed to prevent or treat arsenic-induced lung cancer and Type 2 diabetes.

The funding comes from the National Institute of Environmental Health Sciences. 

Arsenic is a natural metalloid found in soil and is considered one of the most significant contaminants in drinking water globally when ingested at unsafe levels. It 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. 

Donna D. Zhang, PhD, holds the Musil Family Endowed Chair in Drug Discovery at the UArizona College of Pharmacy and is a research member at the UArizona Cancer Center and associate director of the UArizona Superfund Research Center. She will use the funding to further her efforts in untangling the complexities of a protein that could provide the key to treat diseases such as lung cancer that are triggered by injury and inflammation. Her research focuses on nuclear factor erythroid-2-related factor 2, or NRF2. 

Dr. 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.

“Arsenic contamination is a major global health issue, and Dr. Zhang’s research is poised to have a significant impact on improving the health of people in Arizona, across the country and throughout the world,” said University of Arizona President Robert C. Robbins, MD. “I look forward to following Dr. Zhang and her team’s continued progress toward improving treatments and developing potential cures for arsenic-induced diseases.”

Dr. Zhang underscored her focus on lung-related arsenic exposures.

“Three types of cancer primarily are induced by exposure to arsenic: lung, skin and bladder,” she said. “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.” 

Dr. 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.

Dr. 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,” Dr. Zhang said. “We want to rationally target NRF2 with a rigorous, multitiered approach to generate legitimate therapeutic options to mitigate these diseases.”

Research in this publication is supported by the National Institute of Environmental Health Sciences, a unit of the National Institutes of Health, under award No. 1R35ES031575-01.