Johnathan Whetstine, PhD

Lung cancer is the leading cause of cancer-related deaths in the U.S. Aberrant duplication of the genome contributes to a diverse population of cancer cells within lung tumors and increases lung cancer-associated risk and drug resistance. Identifying factors and mechanisms influencing genome stability and drug resistance will impact our ability to treat lung cancer. We discovered multiple enzymes that lead to localized variations in the number of DNA copies in regions linked to drug-resistant lung cancer. We will investigate the molecular details that these enzymes are controlling in order to generate variations in the number of copies of a particular gene, while establishing the impact that additional biological pathways have on cancer gene amplification (copies) in lung cancer. Our research will uncover novel biomarkers in lung cancer and identify unappreciated drug targets to control tumor diversity and resistant lung cancer. 

Update: Aberrant DNA replication and copy generation of the genome contribute to lung tumor heterogeneity, increased cancer-associated risk and drug resistance. For example, DNA amplification and heterogeneity in lung cancer impacts oncogenes and the associated therapeutic response. Our laboratory is determining how replication control and gene amplification is impacting lung cancer-associated copy gains, while aiming to control these events and their associated therapeutic response. These data will identify drug targets for treating DNA amplification and drug resistance. In the past year, we significantly advanced our understanding about how genome replication and amplification occur, while establishing paths to explore in upcoming years.