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Dr. Jonathan Wagner Receives Grant to Study Contribution of Liver Adiposity on Statin Transport Response

STORIES

Dr. Jonathan Wagner Receives Grant to Study Contribution of Liver Adiposity on Statin Transport Response

Headshot of Jonathan B. Wagner, DO
Jonathan B. Wagner, DO
Division Director, Clinical Pharmacology, Toxicology & Therapeutic Innovation; Associate Professor of Pediatrics, University of Missouri-Kansas City School of Medicine
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Jonathan Wagner, DO,  Clinical Pharmacology, Toxicology, and Therapeutic Innovation, received a 1-year, $50,000 Dr. Lauren S. Aaronson Frontiers Clinical and Translational Research Pilot Study Program grant from Frontiers Clinical and Translational Science Institute at the University of Kansas.

Dr. Wagner’s project, “Effects of Liver Adiposity on the Pharmacometabolomics of Statin Disposition and Response in Children,” hopes to determine the contribution of liver adiposity on statin transport and response using a pharmacometabolomics approach.

As Dr. Wagner points out, despite the overall success of statin therapy in children who meet the criteria for obesity, risks of toxicity and treatment failures occur, which may be related to considerable inter-individual variability of circulating statin plasma concentrations and an individual's response to a statin. One such physiologic factor that could contribute to this is liver adiposity, which affects a significant number of obese children and adults. Little is known, though, about how liver adiposity affects hepatocellular processes such as hepatic drug transport (e.g. drug disposition) and cholesterol biosynthesis (e.g. drug response).

Dr. Wagner’s goal is to improve our understanding of the role that liver adiposity has on hepatic drug transport and response serving as a guide to refine not only current statin dosing strategies, but also dosing for other drugs utilized in obese children with comparable drug disposition pathways (anti-diabetic agents, angiotensin receptor blockers).

“If the amount of liver fat predicts differences in amount of 1) markers in the blood responsible associated with drug movement into the liver and 2) markers of drug response after a dose of a statin and this, in turn, predicts risk of side effects and cholesterol-lowering effect, guidelines for prescribing physicians will subsequently be developed to ‘personalize’ dosing for pediatric obese patients. This has the potential for making statin therapy less toxic and more effective for individual patients,” said Dr. Wagner.

Co-investigators include Sherwin Chan, MD, PhD, Valentina Shakhnovich, MD, and Vincent Staggs, PhD.

The Dr. Lauren S. Aaronson Frontiers Clinical and Translational Research Pilot Study Program provides support to grow interdisciplinary, investigator-initiated clinical and translational research across a broad range of scientific disciplines. The Frontiers Pilot Study Program places special emphasis on research targeting the special needs of vulnerable, rural, rare and marginalized groups who historically have not been involved in clinical and translational research.