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 treatments. We have a particular interest in the application of live imaging approaches, including intravital microscopy.
The kidney is a complex and vital organ, with multiple roles in maintaining body homeostasis. Loss of normal kidney function in disease states results in the well-recognized clinical syndromes of acute kidney injury (AKI) and chronic kidney disease (CKD). AKI is associated with substantial morbidity, mortality and healthcare costs. Meanwhile, CKD affects nearly 10% of adults worldwide, is a major risk factor for cardiovascular and bone disease, and is projected to become the 5th leading cause of death by 2040. Despite their medical importance, treatment options for AKI and CKD remain limited.
The kidney comprises of multiple different cell types, arranged in an intricate three dimensional structure. Intravital microscopy provides the possibility to directly observe the behavior of specialized cells and organelles within the functioning organ, how this relates to their spatial position (“four dimensional imaging”), and how they communicate with each other. Moreover, responses to disease causing insults and putative treatments can be followed in real-time, along with subsequent tissue repair and remodeling processes.
Using multiphoton microscopy, custom designed fluorescent probes and computational analysis, we have developed new methods to image various different critical aspects of kidney cell biology in vivo, including solute transport, endocytosis and endo-lysosomal trafficking, protein metabolism, calcium signaling and mitochondrial function. By integrating findings with other orthogonal readouts, such as gene expression data from single cell sequencing, we are deepening understanding of fundamental structure-function relationships in the kidney, the factors and processes that shape these, and the changes that occur in pathological states. Furthermore, we are leveraging this knowledge to design better in vitro experimental models, elucidate unknown disease mechanisms, and formulate new diagnostic and therapeutic strategies for AKI and CKD.