Brendan D. Stamper

Biography

Education: 2010-2012 | Postdoctoral Fellow, Seattle Children’s Research Institute, Seattle, WA 2010 | Doctor of Philosophy, Medicinal Chemistry, University of Washington, Seattle, WA 2002 | Bachelor of Science, Chemistry, Santa Clara University, CA 2002 | Bachelor of Sciences, Combined Sciences, Santa Clara University, CA

Research Interest

Areas of Research & Specialization: My research is focused on projects that utilize comparative genomic, transcriptomic, and proteomic approaches to identify key pathways critical to propagating toxicologic and pathologic outcomes. The adaptability of ‘omic allows my lab to investigate pathologic mechanisms across a wide array of disease states, both inborn and drug-induced. Projects currently underway include mechanistic studies looking at acetaminophen-induced hepatotoxicity, hepatotoxicity associated with various natural products. Acetaminophen project: This project is an ongoing toxicogenomic study investigating the differential toxicity associated with acetaminophen and its regioisomer, 3-hydroxyacetanilide. Acetaminophen is a widely available analgesic and antipyretic, and while considered to be relatively safe at recommended doses, over 50,000 emergency room visits occur annually in the United States due to overdose. At therapeutic levels, the majority of an acetaminophen dose is metabolized to relatively non-toxic products via sulfation and glucuronidation reactions. A smaller percentage of the dose is metabolized to the reactive intermediate, N-acetyl-p-quinoneimine (NAPQI), which is conjugated to glutathione and safely cleared. In overdose situations, NAPQI concentrations rise, resulting in glutathione depletion, protein adduct formation, oxidative stress, and eventually liver injury. Using 3-hydroxyacetanilide as a comparative tool, gene expression profiling studies have been able to identify key biologic targets and pathways associated with the toxic response following acetaminophen overdose. Efforts are currently underway to understand of the role these targets play in signal transduction in hopes of gaining clearer insight into the cellular mechanisms that mediate drug-induced liver injury. In other words: Acetaminophen and AMAP are structurally similar, yet only acetaminophen is toxic at high doses. While acetaminophen and AMAP trigger many of the same effects in cells, some cellular outcomes are different. It’s within these differences that we hope to clarify precisely why high-dose acetaminophen can lead to liver toxicity.