The main topic in the research of Dr. Aperia’s group is to understand the many functional aspects of Na,K-ATPase, the salt pump that is the major determinant of intracellular ion homeostasis and which has recently been shown to also function as a signal transducer.
Studies of Na,K –ATPase has become a hot topic, since a number of monogenetic diseases, associated with cognitive deficits, therapy resistant epilepsy and dystonia, have recently been found to be due to single mutations in the catalytic subunit of the neuronal isoform of Na,K-ATPase. The Aperia has made several pioneering contributions to the understanding of the specific function of neuronal Na,K-ATPase, by identification of its sub-cellular localization in the neuron with STED and PALM microscopy and by demonstrating its functional importance for recovery of intracellular sodium after high neuronal activity by developments of subcellular real time sodium imaging. Currently the group is studying the functional consequences of disease mutations, using a variety of imaging and modeling approaches.
The Aperia group has also pioneered the field of Na,K-ATPase signaling, describing how the endogenous cardiotonic steroid ouabain, which is a specific Na,K-ATPase ligand, triggers an oscillating calcium signal, where the downstream effects are activation of the anti-apoptotic factor Bcl-xL and protection from apoptosis. This signal has been shown to play a major role for protection against apoptosis in fetal malnourishment, in infections with shigatoxin producing E Coli and in chronic kidney disease and we are now seeking to identify the genes activated by the ouabain/Na,K-ATPase calcium signal.