The over-arching goal of our research is to understand how inter-individual variability modulates response to drug, xenobiotic and endobiotic exposure. Past projects in the lab have focused on cytochrome P450 enzyme function in physiology and disease and we have developed a number of genetically engineered knockout mouse lines, including a Cyp4v3 knockout that recapitulates the heritable eye disease, Bietti’s Crystalline Dystrophy. More recently, we are actively engaged in developing alternatives to animal research to address the 3Rs of Toxicology: Reduce, Refine & Replace.
Development of a kidney “organ-on-a-chip".
Our lab is part of a consortium working to develop a functioning human kidney. Members of this consortium include investigators in the School of Pharmacy as well as Departments of Medicine and Bioengineering. The platform for this microphysiological device was developed by Nortis Inc., a UW start-up company. The goal will be to model normal renal function and response to nephrotoxic xenobiotics, incorporating tubular epithelial cells, endothelial cells, and pericytes. Our specific role in this project is development of a proximal tubule utilizing cultures of primary human renal epithelial cells. The ultimate goal will be to integrate a kidney module into a series of organ-on-a-chips, including hepatocytes and enterocytes.
Read more about our upcoming mission to the International Space Station: NASA – Effects of Microgravity on the Structure and Function of Proximal and Distal Tubule MPS
Read more about NCATS’ Tissue Chip for Drug Screening program.
Read the full story covering our “kidney-on-a-chip".
Function of “orphan" CYP4 cells in health and disease.
Two different members of the CYP4 family have been recently linked to seemingly disparate diseases, Lamellar Ichthyosis and Bietti’s Crystalline Dystrophy (CYP4F22 and CYP4V2, respectively). Using a combination of patient-derived cell lines, engineered cells of target tissues, and a mouse knockout model, we are dissecting the biochemical function(s) of CYP4V2 in fatty acid homeostasis. Future work using these same approaches will be applied toward CYP4F22. We say these two diseases are only “seemingly" disparate because another rare genetic condition, Refsum’s disease, affects lipid biochemistry in both the eye and skin, resulting in a pathophysiological state mimicking a combined disruption of CYP4V2 and CYP4F22 function.
Learn more about Bietti’s Crystalline Dystrophy.
Article: Solving Bietti’s Crystalline Dystrophy is mission of Pharmaceutics Professor Ed Kelly