During our Toxicology & Environmental Health Seminar scheduled for this Thursday, March 29th, from 11:45 a.m. – 1:00 p.m. in Field Auditorium, Environment Hall, on Duke’s West Campus, Yu-Ying He, PhD, Associate Professor of Medicine from the University of Chicago, will be presenting a talk entitled “Role of autophagy in environmental carcinogenesis.” Please see below for her talk abstract and bio.
Majority of cancers are associated with exposure to environmental factors. However, the molecular and cellular mechanism in environmental tumorigenesis is not well understood. One of the key regulators for tumorigenesis is macroautophagy (hereafter autophagy), a catabolic process involving lysosomal turnover of proteins and organelles to maintain cellular homeostasis. We focused on two environmental carcinogens: ultraviolet radiation (UV) and arsenic, the known risk factor for skin cancer, as well as other malignancies. Recently we have shown that both UV and arsenic induce autophagy in skin cells. Here we show that autophagy is induced in the epidermis by UV irradiation and epidermis-specific deletion of the essential autophagy gene ATG7 protected against UV-induced inflammation and skin tumorigenesis in mice through regulating COX-2 signaling. ATG7 regulated UV-induced cytokine expression and secretion, and promoted COX-2 expression through both an autonomous mechanism and a non-cell autonomous mechanism. Moreover, ATG7 loss altered energy metabolism and caused accumulation of endoplasmic reticulum (ER) and reduction of ER stress. Inducing ER stress and inhibiting calcium influx into the ER reverses the inflammation and tumorigenesis phenotype in mice with epidermal ATG7 deletion. In ATG7 knockdown keratinocytes, thapsigargin inhibited CRTC1 phosphorylation and increased COX-2 expression through calcium signaling. Overall, our findings demonstrate a crucial role of the autophagy pathways in UV-induced protumorigenic inflammatory microenvironment and skin tumorigenesis.
Yu-Ying He is an Associate Professor of Medicine with Tenure at the University of Chicago. She received her PhD in Chemistry in 2000 from the Chinese Academy of Sciences in China. She then received the Humboldt Research Fellowship working with Dr. Donat-P. Häder at the University of Erlangen-Nuerenburg in Germany. In 2001, she came to NIEHS/NIH for her postdoctoral training with Dr. Colin Chignell. In 2007, she joined the faculty in the Department of Medicine at the University of Chicago. During her research career, Yu-Ying He has received several awards, including the first NIEHS Science Day Early Career Award, the NIH Fellows Award for Research Excellence (FARE), the American Skin Association Research Scholar Award, the Outstanding New Environmental Scientist Award, and Leif B. Sorensen Faculty Research Award.