Selected Ongoing Research Projects:
The Airway Transcriptome: Developing Biomarkers for Lung Cancer and COPD: As one of the central projects within our program, the goal of this study is to profile gene expression changes occurring in intrathoracic (bronchial) and extrathoracic (buccal mucosa and nasal epithelium) airway epithelial cells in the setting of tobacco exposure and develop molecular biomarkers that can predict those smokers at risk for having or developing lung cancer and COPD. This study, performed as part of collaboration with Affymetrix (www. affymetrix.com), has defined the genome-wide impact of smoking and smoking cessation on bronchial airway epithelium (see PNAS manuscript) and has recently identified an airway signature that can serve as a highly sensitive and specific diagnostic in smokers with clinical suspicion of lung cancer.
Mechanisms of regulation of airway epithelial gene expression: Our program has begun to explore genetic, epigenetic and post-transcriptional regulators of gene expression changes within airway epithelial cells. In collaboration with Dr. Douglas Bell at the NIEHS, we are linking gene expression profiles to SNPs in promoter regions of these genes via computational modeling and a novel high-throughput SNP platform. We are also exploring promoter methylation in these cells using a MALDI-TOF Mass Spectometry platform. Finally, we are planning to explore the role of microRNAs in post-transcriptionaly regulating gene expression in these cells using microRNA and whole genome tiling arrays.
Constructing Biological Networks: In collaboration with Dr. James Collins, we are developing novel reverse engineering algorithms to reconstruct gene regulatory networks from airway microarray data in order to define molecular pathways that characterize smokers with lung cancer and COPD.
Airway Proteomics: Using tandem Mass Spectometry in the Proteomics Core Facility (under the direction of Dr. Martin Steffen), we are profiling protein expression changes in airway epithelium and correlating these results to gene expression measurements produced by the experiments described above.
Genomics and Lung Development: In collaboration with Drs. Marty Joyce Brady and Marisa Ramirez, we are profiling gene expression changes that occur in the murine lung in the perinatal period.
Immunopathology of the Nasal Mucosa in Sarcoidosis: Together with Drs. David Serlin and Dr. Jeffrey Berman, we are studying gene expression profiles of nasal epithelium in the setting of sarcoidosis and their relationship to clinical outcome.