Jennifer E. Beane-Ebel, PhD

Biography

Smoking Effects on Airway Epithelial Gene Expression. Given the burden of lung disease created by cigarette smoking, surprisingly few studies had been done in humans to determine how smoking affects the epithelial cells of the pulmonary airways that are exposed to the highest concentrations of cigarette smoke. My research described changes in the airway transcriptome in response to cigarette smoke exposure and smoking cessation. The work represents global molecular characterization of the airway response to smoking and provided insights into the mechanisms leading to reversible and persistent effects of tobacco smoke. Recent single cell RNA sequencing on airway epithelial cells from current and never smokers attributes many of these previously described changes to smoking-associated changes in the abundance of different cell types and the existence of a previously uncharacterized cell type expressing genes persistently altered by smoking.

Early Detection of Lung Cancer via a Gene Expression-Based Diagnostic for Lung Cancer. Lung cancer is the leading cause of death from cancer in the US and the world and the mortality rate remains high due to lack of effective tools to diagnose the disease at an early stage. Histologically normal airway epithelial cells obtained from smokers undergoing bronchoscopy for suspicion of lung cancer were profiled using microarrays, and the data was used to develop a biomarker for the diagnosis of lung cancer. I was subsequently able to show that the gene expression biomarker added predictive value above clinical risk variables and maintained high performance among subjects with intermediate risk for lung cancer. The biomarker was patented and commercialized by Veracyte. We continue to develop lung cancer detection biomarkers derived from the bronchial and nasal epithelium and explore their efficacy in combination with CT image and blood based biomarkrers.

Development and Progression of Lung Squamous Premalignant Lesions. Lung squamous cell cancer (LUSC) arises in the epithelial layer of the bronchial airways and is often preceded by the development of premalignant lesions. The molecular events involved in the progression of premalignant lesions to LUSC are not clearly understood as not all premalignant lesions go on to form carcinoma. Molecular characterization of premalignant lesions and non-lesion areas in the airway of individuals with premalignant lesions (i.e. the “field of injury”) is identifying early events in the process of lung carcinogenesis that can be leverage for lung cancer interception and chemoprevention.

Pathology Image Analysis. Many lung-related studies involve that pathologic evaluation of lung resection tissues or lung biopsies to determine disease severity. The rich data present in pathology slides is rarely incorporated into analyses to identify determinants of disease progression. To address this shortcoming, I am involved in developing methods that utilize H&E-stained digitized whole slide images alone or in combination with molecular data to understand the pathologic and molecular features associated with the early development of lung cancer. These methods complement our analyses of spatial transcriptomic and proteomic data to understand mechanisms of cancer initiation.