For Significant Contributions to NRF2 Biology and Unraveling the Molecular Mechanisms Behind Arsenic-Related Diseases, Donna Zhang Is Being Honored with the 2024 SOT Leading Edge in Basic Science Award

By Marie Fortin posted 24 days ago


This award recognizes a scientist who, based on research, has made a recent (within the last five years), seminal scientific contribution/advance to understanding fundamental mechanisms of toxicity. The recipient should be a respected basic scientist whose research findings are likely to have a pervasive impact on the field of toxicology.

Donna Zhang, PhD, has been honored with the 2024 SOT Leading Edge in Basic Science Award, recognizing her substantial contributions to NRF2 biology and the understanding of molecular mechanisms by which the environmental contaminant arsenic promotes diseases. She is dedicated to translating this knowledge from bench to bedside, focusing on the development of therapeutics that target NRF2.

Dr. Zhang obtained her doctorate in molecular toxicology from the Nelson Institute of Environmental Medicine at New York University in 1997, followed by a postdoctoral fellowship at the DuPont-Haskell Laboratory. From 1999 to 2005, Dr. Zhang was a Research Assistant Professor in the Department of Biochemistry at the University of Missouri. She joined the University of Arizona’s Department of Pharmacology and Toxicology in 2005 and was promoted to full Professor by 2013. As Associate Director of the Superfund Research Program from 2019 to 2022, she played a pivotal role in the program’s successful renewal. In 2020, she became the inaugural Musil Family Endowed Chair in Drug Discovery. In January 2024, Dr. Zhang assumed the esteemed Dr. Herbert A. Wertheim Professor position at the Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, where she continues her work in NRF2 biology and toxicology.

Dr. Zhang’s toxicological research has unraveled the complex interplay between the human body and environmental toxins. Her pioneering work on the cellular NRF2-KEAP1 defense system against environmental insults has made her a leading authority. With over 180 publications, Dr. Zhang’s scholarly impact is evidenced by more than 45,000 citations and an h-index of 78. Her research extends beyond clarifying NRF2’s regulatory mechanisms; it explores its dual roles in diseases such as cancer, diabetes, non-alcoholic fatty liver disease, and Parkinson’s disease. Her seminal work has led to significant advancements in novel therapeutics targeting NRF2.

Dr. Zhang’s research identified KEAP1 as an E3 ubiquitin ligase, a critical regulator that targets NRF2 for ubiquitylation and subsequent degradation. Her insights into KEAP1’s cysteine residues, particularly C151, have been fundamental in understanding their role as sensors of oxidative stress and as switches that regulate the NRF2 pathway in response to environmental insults. She termed this the canonical mechanism of NRF2 activation, central to our comprehension of NRF2’s role in cellular defense. Furthermore, her team has identified and characterized several chemopreventive agents that activate NRF2, showcasing their potential in cancer prevention and the amelioration of diabetic complications.

In 2008, Dr. Zhang uncovered NRF2’s dual role in cancer, demonstrating its contribution to tumor growth and resistance to chemotherapy, and identified brusatol as a potent NRF2 inhibitor. This spurred further research into NRF2’s 'oncogenic' properties. By 2010, her team discovered NRF2’s regulation by the autophagy-related protein p62 through a noncanonical pathway. Her 2013 research illuminated how arsenic prolongs NRF2 activation via this pathway, inadvertently promoting cancer. In 2021, they linked noncanonical NRF2 activation to metabolic diseases, showing how arsenic-induced NRF2 activity can adversely affect glucose metabolism in the liver. Dr. Zhang’s ongoing research focuses on NRF biology, seeking to develop treatments that modulate NRF2 for various diseases and overall health improvement.

Her achievements have been recognized previously by SOT through the SOT Achievement Award in 2012 and the AACT WestChina-Frontier PharmaTech Distinguished Chinese Toxicologist Award from the SOT American Association of Chinese in Toxicology (AACT) Special Interest Group in 2023. An SOT member since 2006, Dr. Zhang is an active member of AACT, the Mechanisms Specialty Section, and the Out Toxicologists and Allies Special Interest Group.

Disclaimer: The information provided in this blog about the awardee(s) is based on the nomination materials provided. This citation is being shared under the Award Committee Chair’s name as part of their official duties and should not be interpreted as their personal or professional opinions.