Bioengineered Microphysiological Systems for Predictive Toxicity Testing
Research Assistant Professor, Department of Pharmaceutics
University of Washington
January 4, 2018
Foege N130A, Wallace H. Coulter Seminar Room
The kidney proximal tubule is the primary site of drug-induced nephrotoxicity. I will describe the development of a 3-dimensional flow-directed proximal tubule microphysiological system (MPS). The kidney MPS recapitulates the synthetic, metabolic and transport activities of kidney proximal tubule cells. This MPS is as an ideal platform for ex vivo modeling of nephrotoxicity. Towards this goal, we have evaluated nephrotoxicity in response to challenge with multiple toxicants, including the heavy metal pollutant cadmium, antisense oligonucleotides, the antibiotic polymyxin B and the Chinese herbal product aristolochic acid. We believe that MPS technologies will have major impacts on predictive toxicity testing and human risk assessment. Animal and in vitro systems do not always faithfully recapitulate drug and xenobiotic responses in the clinic or occupational/environmental exposures, respectively. MPS technologies will refine safety assessment and reduce our need for surrogate animal testing. We are currently evaluating this technology for disease modeling, including organ responses in the extreme environment of microgravity as a means for accelerating pathophysiology.
Dr. Kelly earned his PhD in Biochemistry from the University of Washington in the laboratory of Richard Palmiter. Following a postdoctoral fellowship in molecular toxicology at UW with David Eaton, he ventured into Biotech, managing a Preclinical group at Targeted Genetics Corporation, evaluating the safety and efficacy of AAV-based gene therapies.
Upon his return to academia, his research interests have stayed within the realm of preclinical biology. His lab works on developing novel models to study normal human physiology and disease states, with a particular focus on cytochrome P450 enzymes and their role in endobiotic/xenobiotic metabolism.
The majority of his lab works on ex vivo modeling of human organ physiology and toxicological responses to drug/xenobiotic challenge. This project makes use of “organs on chips” or microphysiological systems (MPS) populated with primary and stem-cell derived cell types to recapitulate two key ADME organs, the liver and kidney. Recent work is extending MPS technologies to model human diseases, as well as how organs respond to the extreme environment of microgravity on the International Space Station. Dr. Kelly holds the position of Associate Professor in the Department of Pharmaceutics, Adjunct Associate Professor in the Department of Environmental and Occupational Health Sciences and also serves as Co-Director of the Pharmaceutical Bioengineering Program.