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.Read more
Areas of interest
- gas chromatography mass spectrometery; liquid chromatography mass spectrometry; drug metabolism;drug development
- Ph.D., Northwestern University School of Medicine, Chicago Illinois United States 1979
- B.S., Bradley University, Peoria Illinois United States 1974
Memberships and associations
- SOM-Physiology &Pharmacology DepartmentPhysiology &PharmacologyProgram in Molecular &Cellular Biosciences
- "Longitudinal study on the use of dried blood spots for home monitoring in children after kidney transplantation." Pediatric Transplantation In: , 2017.
- "Lipoic acid pharmacokinetics at baseline and 1 year in secondary progressive MS." Neurology: Neuroimmunology and NeuroInflammation In: , Vol. 4, No. 5, 380, 2017.
- "A comparison of salivary testosterone measurement using immunoassays and tandem mass spectrometry." Psychoneuroendocrinology In: , Vol. 71, 01.09.2016, p. 180-188.
- "Diphenylether-Modified 1,2-Diamines with Improved Drug Properties for Development against Mycobacterium tuberculosis." ACS Infectious Diseases In: , Vol. 2, No. 7, 08.07.2016, p. 500-508.
- "A role for adenine nucleotides in the sensing mechanism to purine starvation in Leishmania donovani." Molecular Microbiology In: , Vol. 101, No. 2, 01.07.2016, p. 299-313.
- "Polyphenon E, non-futile at neuroprotection in multiple sclerosis but unpredictably hepatotoxic : Phase I single group and phase II randomized placebo-controlled studies." Journal of the neurological sciences In: , Vol. 358, No. 1-2, 15.11.2015, p. 46-52.
- "A phase II study of sulforaphane-rich broccoli sprout extracts in men with recurrent prostate cancer." Investigational New Drugs In: , Vol. 33, No. 2, 01.04.2015, p. 480-489.
- "Threshold levels of ABL tyrosine kinase inhibitors retained in chronic myeloid leukemia cells determine their commitment to apoptosis." Cancer Research In: , Vol. 73, No. 11, 01.06.2013, p. 3356-3370.
- "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 In: , Vol. 926, 01.05.2013, p. 54-61.
- "Effect of the ethinylestradiol/levonorgestrel combined oral contraceptive on the activity of cytochrome P4503A in obese women." British Journal of Clinical Pharmacology In: , Vol. 74, No. 3, 09.2012, p. 510-514.
- "Naloxone pro-drug rescues morphine induced respiratory depression in Sprague-Dawley rats." Respiratory Physiology and Neurobiology In: , Vol. 180, No. 1, 15.01.2012, p. 52-60.
- "The effects of nitrogen-heme-iron coordination on substrate affinities for cytochrome P450 2E1." Chemico-Biological Interactions In: , Vol. 193, No. 1, 15.08.2011, p. 50-56.
- "Ubiquitin-dependent proteasomal degradation of human liver cytochrome P450 2E1 : Identification of sites targeted for phosphorylation and ubiquitination." Journal of Biological Chemistry In: , Vol. 286, No. 11, 18.03.2011, p. 9443-9456.
- "Optimization of endochin-like quinolones for antimalarial activity." Experimental Parasitology In: , Vol. 127, No. 2, 02.2011, p. 545-551.
- "Interstrain differences in the liver effects of trichloroethylene in a multistrain panel of inbred mice." Toxicological Sciences In: , Vol. 120, No. 1, 2011, p. 206-217.
- "Mechanism for prevention of alcohol-induced liver injury by dietary methyl donors." Toxicological Sciences In: , Vol. 115, No. 1, 05.2010, p. 131-139.
- "Pharmacokinetic study of acid in multiple sclerosis : Comparing mice and human pharmacokinetic parameters." Multiple Sclerosis In: , Vol. 16, No. 4, 04.2010, p. 387-397.
- "Paired assessment of volatile anesthetic voncentrations with synaptic actions recorded in vitro." PLoS One In: , Vol. 3, No. 10, e3372, 08.10.2008.
- "Soluble epoxide hydrolase gene deletion is protective against experimental cerebral ischemia." Stroke In: , Vol. 39, No. 7, 07.2008, p. 2073-2078.
- "Isoflurane differentially modulates inhibitory and excitatory synaptic transmission to the solitary tract nucleus." Anesthesiology In: , Vol. 108, No. 4, 04.2008, p. 675-683.
- "Polymorphisms in the human soluble epoxide hydrolase gene EPHX2 linked to neuronal survival after ischemic injury." Journal of Neuroscience In: , Vol. 27, No. 17, 25.04.2007, p. 4642-4649.
- "Alcohol metabolism's damaging effects on the cell : A focus on reactive oxygen generation by the enzyme cytochrome P450 2E1." Alcohol Research and Health In: , Vol. 29, No. 4, 2006, p. 274-280.
- "Effect of pregnancy on the pharmacokinetics of paclitaxel : A case report." Clinical Breast Cancer In: , Vol. 7, No. 4, 2006, p. 342-344.
- "Steatohepatitis induced by intragastric overfeeding in mice." Hepatology In: , Vol. 42, No. 4, 10.2005, p. 905-914.
- "Use of CYP2E1-transfected human liver cell lines in elucidating the actions of ethanol." Alcoholism: Clinical and Experimental Research In: , Vol. 29, No. 9, 09.2005, p. 1726-1734.
- "Centella asiatica accelerates nerve regeneration upon oral administration and contains multiple active fractions increasing neurite elongation in-vitro." Journal of Pharmacy and Pharmacology In: , Vol. 57, No. 9, 09.2005, p. 1221-1229.
- "Hepatoprotective mechanisms of Yan-gan-wan." Hepatology Research In: , Vol. 32, No. 4, 08.2005, p. 202-212.
- "Cytochrome P450 CYP2E1, but not nicotinamide adenine dinucleotide phosphate oxidase, is required for ethanol-induced oxidative DNA damage in rodent liver." Hepatology In: , Vol. 41, No. 2, 02.2005, p. 336-344.
- "A phase I study of 5-fluorouracil, leucovorin, and celecoxib in patients with incurable colorectal cancer." Prostaglandins and Other Lipid Mediators In: , Vol. 75, No. 1-4, 01.2005, p. 169-172.
- "Proteasome-dependent degradation of cytochromes P450 2E1 and 2B1 expressed in tetracycline-regulated HeLa cells." Toxicology and Applied Pharmacology In: , Vol. 199, No. 3, 15.09.2004, p. 332-343.