Our lab has a long-standing interest in tumor initiation and progression. A better understanding on how tumors evolve over time with respect to genetic, epigenetic, and gene expression changes will elucidate the molecular mechanisms underlying the aggressiveness and fatality of the disease and provide insights for tumor initiation, metastasis, and drug resistance. Our research focuses on the two major subtypes of lung cancer, namely non-small cell lung cancer (lung adenocarcinoma) and small cell lung cancer. We are currently identifying and characterizing protein-coding and non-coding (e.g. microRNAs) gene regulation in tumor progression, invasion and metastasis, including loss of the master pulmonary differentiation factor Nkx2-1, gain of the embryonic proto-oncogene Hmga2, isoform switching of the invadopodia component Tks5, and misregulation of the miR-200 family of microRNAs.
We are extending this research by investigating the role of various developmental pathways during tumor initiation and progression. These pathways are critical for tumor maintenance, evolution and possibly resistance to existing cancer therapies. Finally, we are also elucidating the impact of physiologic risk factors on lung tumorigenesis, which remain poorly understood. These risk factors are a major consequence of modern lifestyle and there are extensive epidemiological studies linking them to various cancers, including lung cancer.
Invadopodia are proteolytic cellular protrusions that can degrade various components of extracellular matrix and are thought to enable tumor cells to metastasize. Shown here is an immunofluorescence image of metastatic lung adenocarcinoma cells with abundant invadopodia. The foci of invadopodia contain F-actin (red) and cortactin (green).