Photo of Dennis R Koop, Ph.D.

Dennis R Koop Ph.D.

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.

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Areas of interest

  • gas chromatography mass spectrometery; liquid chromatography mass spectrometry; drug metabolism;drug development

Education

  • B.S., Bradley University, Peoria Illinois United States 1974
  • Ph.D., Northwestern University School of Medicine, Chicago Illinois United States 1979

Memberships and associations

  • SOM-Physiology &Pharmacology DepartmentPhysiology &PharmacologyProgram in Molecular &Cellular Biosciences

Publications

  • "Inhibition of ethanol-inducible cytochrome P450IIE1 by 3-amino-1,2,4-triazole" Chemical Research in Toxicology  1990
  • "Kinetics of the hydroperoxide-dependent dealkylation reactions catalyzed by rabbit liver microsomal cytochrome P-450." Journal of Biological Chemistry October 25 1980
  • "Alcohol metabolism and toxicity" Toxicological Sciences  1984
  • "Ubiquitin-dependent proteasomal degradation of human liver cytochrome P450 2E1" Journal of Biological Chemistry March 18 2011
  • "A phase I study of 5-fluorouracil, leucovorin, and celecoxib in patients with incurable colorectal cancer" Prostaglandins and Other Lipid Mediators January 2005
  • "Comparison of six rabbit liver cytochrome P-450 isozymes in formation of a reactive metabolite of acetaminophen" Biochemical and Biophysical Research Communications April 15 1983
  • "Use of CYP2E1-transfected human liver cell lines in elucidating the actions of ethanol" Alcoholism: Clinical and Experimental Research September 2005
  • "Attenuation of CCl4-induced hepatic fibrosis by GdCl3 treatment or dietary glycine" American Journal of Physiology - Renal Fluid and Electrolyte Physiology  2001
  • "Alcohol metabolism and toxicity" Toxicological Sciences April 1984
  • "Tightly regulated and inducible expression of rabbit CYP2E1 using a tetracycline-controlled expression system" Drug Metabolism and Disposition  1999
  • "Role of isosafrole as complexing agent and inducer of P-450LM4 in rabbit liver microsomes" Biochemical and Biophysical Research Communications September 16 1982
  • "Hepatoprotective mechanisms of Yan-gan-wan" Hepatology Research August 2005
  • "Liver microsomal metabolism of N-methylcarbazole" Molecular Pharmacology  1980
  • "Analysis of tacrolimus and creatinine from a single dried blood spot using liquid chromatography tandem mass spectrometry" Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences May 1 2013
  • "Enzymatic determinants of the substrate specificity of CYP2C9" Biochemistry March 16 1999
  • "Degradation of cytochrome P450 2E1" Archives of Biochemistry and Biophysics February 14 1992
  • "Specificity in the activation and inhibition by flavonoids of benzo[a]pyrene hydroxylation by cytochrome P-450 isozymes from rabbit liver microsomes" Journal of Biological Chemistry  1981
  • "Paired assessment of volatile anesthetic voncentrations with synaptic actions recorded in vitro" PLoS One October 8 2008
  • "Forum original research communication" Antioxidants and Redox Signaling October 2002
  • "Ethanol-inducible cytochrome p450 in rabbits metabolizes enflurane" British Journal of Anaesthesia July 1989
  • "Polymorphisms in the human soluble epoxide hydrolase gene EPHX2 linked to neuronal survival after ischemic injury" Journal of Neuroscience April 25 2007
  • "Metabolism of nitrosamines by purified cytochrome P-450 isozymes from rabbit liver" Federation Proceedings  1984
  • "Centella asiatica accelerates nerve regeneration upon oral administration and contains multiple active fractions increasing neurite elongation in-vitro" Journal of Pharmacy and Pharmacology September 2005
  • "Role of cytochrome P-450 2E1 in ethanol-, carbon tetrachloride- and iron-dependent microsomal lipid peroxidation" Hepatology October 1992
  • "Oxidative and reductive metabolism by cytochrome P450 2E1" FASEB Journal January 6 1992
  • "The role of cytochrome P450 2C3 in rabbit liver microsomal metabolism of 1-nitropyrene and 3-nitrofluoranthene" Journal of Biochemical and Molecular Toxicology April 1994
  • "P-450-dependent arachidonic acid metabolism in rabbit olfactory microsomes" Journal of Pharmacology and Experimental Therapeutics  1992
  • "Oxidation of 1,3-butadiene to (R)- and (S)-butadiene monoxide by purified recombinant cytochrome P450 2E1 from rabbit, rat and human" Toxicology Letters March 16 1998
  • "Use of monoclonal antibody probes against rat hepatic cytochromes P-450c and P-450d to detect immunochemically related isozymes in liver microsomes from different species" Archives of Biochemistry and Biophysics November 15 1984
  • "Cytochrome P450 CYP2E1, but not nicotinamide adenine dinucleotide phosphate oxidase, is required for ethanol-induced oxidative DNA damage in rodent liver" Hepatology February 2005

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