Mechanisms of protein homeostasis and energy metabolism in cancer.
Our research focusses on basic mechanisms of protein and energy homeostasis, their role in tumorigenesis, and their utility as cancer drug targets. Our work has concentrated on conserved pathways regulating protein homeostasis and associated stress response pathways. We have been pursuing these lines of investigation in human cell lines as well as in genetic models ranging from yeast to the mouse. Current projects are geared toward deciphering energy and protein metabolism as mutually intertwined processes critical for the generation of biomass from nutrients – and thus the growth and proliferation of cancer cells. We concentrate on mitochondrial complex I and the translation initiation factor eIF3, two macromolecular complexes at the cross-roads of these processes. Much remains to be learned about their exact functions and integration in cancer. Our goal over the next 5 – 10 years is to advance our functional understanding of these complexes to the point where we can develop strategies for rationally interfering with their essential roles in tumorigenesis.