Dr. Donna D. Zhang’s research focuses on developing pharmaceuticals to prevent or treat exposure to arsenic, which has affected more than 160 million people worldwide.
TUCSON, Ariz. – 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 and 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.
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The University of Arizona Cancer Center is the only National Cancer Institute-designated Comprehensive Cancer Center with headquarters in Arizona. The UArizona Cancer Center is supported by NCI Cancer Center Support Grant No. CA023074. With primary locations at the University of Arizona in Tucson and at Dignity Health St. Joseph’s Hospital and Medical Center in Phoenix, the Arizona Cancer Center has more than a dozen research and education offices throughout the state, with more than 300 physicians and scientists working together to prevent and cure cancer. For more information: cancercenter.arizona.edu (Follow us: YouTube).
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The University of Arizona College of Pharmacy is the premier pharmacy college in the Southwest, and one of the top in the nation, focused on drug discovery, toxicology, pharmaceutics, health outcomes and sciences, pharmaceutical education and research through interprofessional training and collaborative public/private partnerships. Preparing pharmacists and pharmaceutical scientists in undergraduate, professional, graduate and post-doctoral programs, the college embraces an entrepreneurial spirit, providing tailored educational opportunities to broaden students' experiences. Established 72 years ago as the first health sciences college at UArizona, the college has a long history of improving science and health, both in Arizona and around the world. It is currently ranked No. 8 among the nation’s 143 colleges of pharmacy by the American Association of Colleges of Pharmacy. For more information: pharmacy.arizona.edu (Follow us: Facebook | Twitter | Instagram | YouTube).
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The University of Arizona Health Sciences is the statewide leader in biomedical research and health professions training. UArizona Health Sciences includes the Colleges of Medicine (Tucson and Phoenix), Nursing, Pharmacy, and the Mel and Enid Zuckerman College of Public Health, with main campus locations in Tucson and the Phoenix Biomedical Campus in downtown Phoenix. From these vantage points, Health Sciences reaches across the state of Arizona, the greater Southwest and around the world to provide next-generation education, research and outreach. A major economic engine, Health Sciences employs nearly 5,000 people, has approximately 4,000 students and 900 faculty members, and garners $200 million in research grants and contracts annually. For more information: uahs.arizona.edu (Follow us: Facebook | Twitter | YouTube | LinkedIn | Instagram).