We are interested in how heavy metals interact with biological systems to cause toxicity. Our central project focuses on the heavy metal cadmium and its effects in the kidney. Humans are commonly exposed to cadmium through contaminated food stuff and/or through smoking. The heavy metal has the highest accumulation potential in the renal proximal tubule cells in comparison at all tissues of the human body where the metal exhibits and overall half-life of 30 years. We are investigating how this leads to demise of tubular functioning, inflammation, fibrosis and eventually contributes to chronic kidney disease. We primarily use in vitro cell models consisting of either human proximal tubule cells isolated from human kidney or immortalized proximal tubule cells transfected with various genes thought to contribute to handling of this metal. We are currently assessing the role of stem cells in these models and how they contribute to regeneration of the proximal tubule. We are also studying how high glucose concentrations seen in diabetes can contribute to toxic responses of the kidney and lead to a progression to end-stage renal disease.
One molecule that we have focused on in the past is the protein primarily responsible for sequestration of cadmium, metallothionein. We have characterized this gene family in the renal system and discovered that a unique isoform of this gene family, metallothionein-3, contributes to the maintenance of epithelial morphology and can counter the mesenchymal-to-epithelial transition that can occur in some toxic responses.
Through collaborations with other members in the department, we also study how cadmium and arsenic lead to the formation of bladder cancer.