2021 Lung Cancer Research Foundation Pilot Grant
Aria Vaishnavi, PhD
University of Utah
Elucidating the molecular mechanisms of radon-induced lung cancer through a novel mouse model
Chronic exposure to inhaled radon gas is estimated to cause 21,000 lung cancer deaths in the US annually, making it the second leading cause of lung cancer, and the leading cause of lung cancer in never smokers (LCINS). Despite this, the precise molecular, cellular and genetic changes that occur in the lung epithelium following chronic radon exposure to environmentally-relevant levels of radon gas are poorly characterized. Moreover, there are no reliable ways to identify radon-induced lung cancer in patients.
Hence, to address this critical knowledge gap, we plan to develop genetically engineered, as well as human patient-derived mouse models that will enable direct assessment of the molecular, cellular and genetic changes that occur in the lung following chronic exposure to environmentally relevant levels of radon. The long-term goals of this work are to: dissect out a molecular signature or imprint from chronic radon exposure, novel biomarkers in mice and humans exposed to chronic levels of radon, as well as to identify critical and common genetic (oncogenic) alterations that occur at key disease stages. These may be used to identify human lung cancer patients that harbor radon-induced disease in the clinic. An improved understanding of the molecular mechanisms that drive radon-induced lung cancer may result in new or improved therapeutic strategies in this poorly understood disease.