Bio: Dr. Chengfeng Yang is a Professor at Stony Brook Cancer Center and the Department of Pathology, Renaissance School of Medicine, Stony Brook University. Dr. Yang received his medical degree and PhD from Tongji Medical University and National University of Singapore, respectively. After his postdoctoral training at New York University and University of Pennsylvania, Dr. Yang started his independent academic career at Michigan State University. Before joining Stony Brook University as a Professor, Dr. Yang also served as a tenured Professor at University of Kentucky and Case Western Reserve University. Dr. Yang’s research focuses on studying the molecular mechanism of environmental carcinogens especially metal carcinogen exposure-induced lung cancer. Dr. Yang studies how dysregulations of RNAs including coding and non-coding RNAs contribute to environmental carcinogenesis. Dr. Yang’s research has been continuously supported by multiple R01 grants from NIEHS since 2010. Dr. Yang is currently serving as an Associate Editor of Toxicological Sciences, the official journal of the Society of Toxicology (SOT).

Abstract: Hexavalent chromium [Cr(VI)] is a trace element. Due to natural and human activities, a significant amount of Cr(VI) has been released into the environment. Based on the findings from human epidemiology and laboratory animal studies, the International Agency for Research on Cancer (IARC) classified Cr(VI) as a Group I carcinogen for humans. Chronic Cr(VI) exposure causes lung cancer in humans, however, the mechanism of Cr(VI) carcinogenesis remains largely unknown. By using human bronchial epithelial cell culture and mouse lug tumorigenesis models, we found that the expression of long noncoding RNA ABHD11-AS1 is significantly up-regulated in chronic Cr(VI) exposure-transformed cells and Cr(VI) exposure-induced lung tumors in mice. It was further determined that up-regulation of ABHD11-AS1 expression by chronic Cr(VI) exposure activates the non-canonical NF-κB signaling pathway. The expression and nuclear localization of the non-canonical NF-κB pathway transcription factor RelB were significantly increased in chronic Cr(VI) exposure-transformed human bronchial epithelial cells and mouse lung tumor tissues. Mechanistic studies showed that chronic Cr(VI) exposure activates the non-canonical NF-κB pathway by ABHD11-AS1 and USP15-mediated down-regulation of TRAF3. It was further determined that activation of the non-canonical NFκB pathway by chronic Cr(VI) exposure up-regulates the expression of the immune check point molecule PD-L1 expression. Given the important role of PD-L1-mediated immune suppression in cancer, our findings suggest that up-regulation of PD-L1 expression may contribute to Cr(VI) carcinogenesis.