The overall aim of our group is to utilize cutting-edge research techniques to elucidate cellular mechanisms of kidney diseases, with the long-term goal of developing new therapeutic strategies. We have a particular interest in the application of live imaging approaches, including intravital microscopy, and our studies are focused mainly (but not exclusively) on the roles of mitochondria in kidney disease pathways.
Acute kidney injury (AKI) is associated with significant morbidity and mortality; it therefore represents a major public health burden. Frequent causes include ischemia-reperfusion injury, sepsis and drug toxicity. Unfortunately, understanding of the underlying disease mechanisms remains incomplete, and there are currently very few effective treatment options. Kidney tubular cells contain a high density of mitochondria, which are thought to have a central role in the pathogenesis of most types of AKI. Mitochondria are complex and dynamic organelles that have numerous important functions. Thus, mitochondrial injury can potentially be deleterious to kidney cells in a variety of different ways, many of which have yet to be fully elucidated. Progress in this area has been limited historically by a lack of appropriate methods to investigate mitochondrial behavior in their natural environment.
We have developed live imaging techniques - using a form of fluorescence imaging called multiphoton microscopy - which enable the study of mitochondrial structure, function and dynamics in intact kidney tissue, including in living rodents. Using this approach, we are gaining new insights into how mitochondria in the kidney actually behave in vivo, how their function is adapted to the specific needs of the host cell, and how they respond in real-time to disease causing insults.