Bio: Dr. Zhishan Wang is a Professor of Research at Stony Brook Cancer Center and the Department of Pathology, Renaissance School of Medicine, Stony Brook University. Dr. Wang received her medical degree and PhD from Tongji Medical University and postdoctoral training at Emory University and University of Alabama at Birmingham. Before joining Stony Brook University as a Professor of Research, Dr. Wang served as Assistant and Associate Professor at University of Kentucky and Case Western Reserve University, respectively. Dr. Wang’s research focuses on understanding how exposure to environmental carcinogens especially metal carcinogens and exposure to metal carcinogens plus other chemical carcinogens cause lung cancer. Dr. Wang’s environmental carcinogenesis mechanism studies focus on epigenetic dysregulations including non-coding RNAs, RNA epigenetic or RNA modification dysregulations. In addition to study epigenetic dysregulations, Dr. Wang also studies the role of gut microbiota dysbiosis in environmental carcinogenesis. Her research has been supported by multiple NIH R01 grants and private foundation grants.

Abstract: Chronic exposure to low levels of arsenic causes lung cancer in humans, however, the mechanism of arsenic carcinogenesis has not been well understood. Epidemiology studies showed that arsenic-exposed people who were cigarette smokers had a significantly higher lung cancer risk than those who were non-smokers, indicating that arsenic exposure and cigarette smoking act synergistically in increasing the risk of lung cancer. Since benzo(a)pyrene (BaP) is one of the major carcinogens in cigarette smoke, it was speculated that the synergistic effect of arsenic exposure and cigarette smoking on lung cancer risk could be due to the combined effect of arsenic and BaP co-exposure. We investigated the combined effect of arsenic and BaP co-exposure using cell culture and mouse models. It was found that arsenic and BaP co-exposure exhibits a synergistic effect in inducing cell malignant transformation and lung tumorigenesis in mice. Mechanistic studies revealed that arsenic and BaP co-exposure causes RNA m6A methylation dysregulations evidenced by the significantly higher levels of the RNA m6A methyltransferase METTL3 expression and total RNA m6A methylation levels in arsenic and BaP co-exposure-transformed cells. Further functional studies demonstrated that knocking down the expression of METTL3 in arsenic and BaP co-exposure-transformed cells significantly reduced their transformed malignant phenotypes and tumorigenesis. These findings suggest that RNA m6A methylation dysregulations may play an important role in the synergistic carcinogenic effect of arsenic and BaP co-exposure.