We are investigating the role ion channels and ion transporters play in tumor and immune cell migration. In particular, we focus on Ca2+ sensitive K+ channels, TRP channels, and the Na+/H+ exchanger. The key question addressed by our research is: Why are these ion transport proteins required for cell migration? To this end we apply predominantly imaging techniques such as time-lapse videomicroscopy, live-cell fluorescence microscopy, TIRF microscopy and ionic imaging and atomic force microscopy.
1. Function of transport proteins in pancreatic stellate cells
This project is pursued within the framework of the European Marie Skłodowska Curie Innovative Training Network "pHioniC". It was originally initiated within the "IonTraC"network (2011-15) that was built around the study of ion transport proteins in pancreatic ductal adenocarcinoma (PDAC). We are studying how the crosstalk between ion channels and transporters in pancreatic stellate cells and the PDAC microenvironment drives the progression of the disease.
3. TRPM2 channel in neutrophil function
Neutrophil activation comprises multiple functions such as extravasation, chemotaxis, ROS production or phagocytosis. It is usually initiated by the binding of chemokines and chemoattractants to their G-protein coupled receptors (GPCRs). Dysfunction of any of the neutrophil defense mechanism may have serious consequences - from prolonged infection to autoimmune diseases.
TRPM2 is a Na+ and Ca2+-permeable channel expressed in neutrophils. The function of neutrophils lacking TRPM2 channels is disturbed, but the causes are not yet fully understood. Here we analyze TRPM2 mechanism of action and its role in neutrophil chemotaxis and ion homeostasis.
4. KCa3.1 channels in the progression of non-small cell lung cancer (NSCLC)
This project builds upon mounting evidence that ion channels underlie many of the hallmarks of cancer. They are expressed aberrantly in cancer and are central players in proliferation, apoptosis, angiogenesis, cell-matrix interaction and migration/invasion. Here, we want to address the question whether KCa3.1 channels contribute to the development of an invasive, metastatic phenotype of NSCLC cells and thereby promote the progression of the disease.
5. Nanomechanics of melanoma cell-cell adhesion
A melanoma cell attached to the AFM cantilever is brought in contact with another adherent melanoma cell. Upon cantilever retraction and separation of the cells, the adhesive interaction forces can be quantified. Cartoon by F. Ludwig
6. Mechano-signaling in pancreatic stellate cells
In the healthy pancreas, pancreatic stellate cells (PSCs) are enveloped in a soft meshwork of extracellular matrix, mainly next to acinar or ductal cells. In chronic pancreatitis and pancratic cancer, the environment of these cells changes dramatically to a stiff, fibrous tissue, which provokes functional changes in PSCs. The exact nature of these changes is yet unknown and thus we aim to elucidate the key sensors of mechanical stress in PSCs and what cellular reactions they initiate.
1. Fels B et al., Eur Biophys J. 2016