From mucolipidosis type IV to Ebola: insights into function and pharmacology of endolysosomal cation channels

My group is interested in the analysis of cation channels of the TRP (transient receptor potential) superfamily within the trafficking network of the endolysosomal system. Lysosomal dysfunction can result in endolysosomal storage disorders (LSDs) such as mucolipidoses or mucopolysaccharidoses but is also implicated in metabolic diseases, the development of neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease, retinal diseases and pigmentation disorders, trace metal deficiencies, infectious diseases and cancer. Highly critical for the proper function of lysosomes, endosomes, and lysosome-related organelles (LROs) is the tight regulation of various fusion and fission processes, the regulation of proton and other cation concentrations within the endolysosomal system (ES), the regulation of autophagy processes as well as endolysosomal phago- and exocytosis processes. TRPML cation channels (TRPML1, 2 and 3) and Two-pore channels (TPCs) have recently emerged as important regulators of such processes within the ES and appear to be essential for a proper communication between the various endolysosomal vesicles. We use endolysosomal patch-clamp techniques, molecular and cellular biology techniques, pharmacological approaches as well as genetic mouse models to study the physiological roles and activation mechanisms of these ion channels in-depth.