Lung disease is one of the leading causes of death in the world. The general aim of the laboratory of thoracic surgery is to develop new treatment options for the malignant lung. The role of stem cells in lung injury, repair, remodelling and tumorigenesis is still unclear. Thus, we are specifically focussing on stem cells in the context of lung regeneration and cancer.
In lung cancer, tumor initiating cells (TIC)s were identified and subsequent analysis indicated that the DNA damage response pathway is deregulated in TICs. Our aim is to identify TICs in primary lung cancer samples and to characterize differentially regulated DNA damage response factors of TICs, which will allow us to identify novel targets for pharmacological or genetic intervention to treat lung cancer.
Resistance to chemotherapy and ensuing tumor relapse are common and the major cause of therapeutic failure and mortality in the clinic. Our previous findings indicate that resistance of tumors to chemotherapy is linked to tumor subsets with stem cell-like features, i.e. TICs. We intend to isolate chemotherapy resistant cells from primary patient samples after exposure to chemotherapeutics used in the clinical setting. Characterization of the selected subpopulation will provide insights into the mechanism by which chemoresistance occurs in vivo, thereby uncovering new therapeutic targets in human lung cancer.
There is emerging evidence to suggest that the tumor (mesenchymal) microenvironment acts in concert with the cancer cell-centric changes driving tumor phenotype. Therefore, our aim is to translate our findings using a combined pharmacological and genetic approach using patient-derived samples and inducible mouse models of human lung cancer to determine the potential of this tumor-derived mesenchymal subset to serve as a novel therapeutic target in lung cancer.
In an additional project, we are interested in identifying stem and progenitor cells that are critically involved in alveolar regeneration. To achieve this, we aim to utilize primary human samples and genetic fate mapping tools to identify cellular hierarchies in alveolar development and cell fate during injury and alveolar regeneration.
More details regarding our projects are available at: