Dennis R. Koop, PhD
SOM-Physiology & Pharmacology Department
Background & Education
Ph.D. 1979, Northwestern University Medical School
B.S. 1974, Bradley University
I was appointed the Director of the Bioanalytical Shared Resource/Pharmacokinetics Core (BSR/PKCore) at OHSU in 2004. My research interests are now focused on the development and implementation of liquid chromatography tandem mass spectrometry (LC-MS/MS) methods for the analysis of small molecules from a wide variety of biological sources for investigators at OHSU.
Previous research in my laboratory was focused on characterizing the catalytic activity of cytochromes P450 (CYPs) in the metabolism of arachidonic acid. One of the first assays established in the BSR/PKCore was for the analysis of oxidized arachidonic acid metabolites. We developed an assay to quantify 57 different oxidized metabolites of polyunsaturated fatty acids including the full complement of diols, epoxides, and mono-hydroxylated metabolites produced from arachidonic acid by P450 as well as lipooxygenase, cyclooxygenase and non-enzymic markers of oxidative stress, the isoprostanes. The methods are being used to characterize metabolites from cerebral spinal fluid, brain, endothelial cells, other tissue extracts, plasma, urine and cell culture systems. I maintain an interest in drug metabolism. A significant focus of BSR/PKCore activity is to support new medical entitiy development. In vitro hepatic metabolic stability assays and metabolite identification using information dependent acquisition with various survey scans are performed. In addition, in vivo P450 phenotyping assays such as midazolam and tolbutamide for CYP3A4 and 2C9, respectively, were developed.
A major focus of the laboratory is to facilitate pharmacokinetic studies in animal models and Phase 1 trials in humans. Significant efforts are geared to establish dried blood spot methodologies. Such techniques reduce the number of animals needed in kinetic studies and also facilitate in home drug monitoring for Phase 1 clinical trials and when translated to the clinical laboratory can be used for therapeutic drug monitoring.