Jamshedur Rahman, PhD

Molecular signatures in the airways of individuals at-risk for lung cancer

The airway epithelium represents the field of carcinogenesis where stochastic DNA alterations by tobacco carcinogens and environmental agents cause lung tumor formation. We are investigating these alterations by deep targeted and whole exome sequencing of the cytologically normal bronchial epithelial cells collected from at-risk individuals. Our hypothesis is that cytologically normal airway epithelial cells of individuals at-risk for lung cancer harbor driver gene mutations. Based on our previously published results on metabolic reprogramming in the airway epithelium of at-risk individuals, we are also validating selected candidate proteomic determinants of lung cancer risk. The overall goal of my projects is to identify the molecular signatures of lung tumorigenesis in the airways of risk stratified individuals. These signatures will provide tools for the risk assessment and early detection of lung cancer as well as assist in the formulation of effective surveillance strategies. To understand the link between metabolic reprogramming and genomic instability resulting from the driver gene mutations, we are developing an in vitro model of the genetically modified human bronchial epithelial cells. This in vitro model will facilitate dissecting mechanisms of cellular transformation at the earliest point of lung tumorigenesis.