John D. Clarke, Ph.D.


Education
Ph.D. in molecular and cellular biology, Oregon State University, Corvallis, Oregon

Bachelor of Science in biology, Brigham Young University-Idaho, Rexburg, Idaho

Fellowships & Additional Training
Postdoctoral scholar, pharmacology and toxicology, University of Arizona, Tucson, Arizona

Research
Toxicities from xenobiotic exposures are a significant burden on human health. These exposures occur both intentionally (drugs and dietary supplements) and unintentionally (environmental contamination and naturally occurring toxins), and there are several factors in individual variability that determine who is at greater risk for these toxicities. Clarke's laboratory seeks to address two fundamental research questions regarding populations at risk for toxicities:

  • Precision medicine: This project investigates how perturbations in two or more factors in drug absorption, distribution, metabolism, and excretion affect drug exposures and toxicities.
  • Toxicities in progressive nonalcoholic fatty liver disease (NAFLD): NAFLD is the most common liver disease in the United States that progresses through multiple stages including simple fatty liver, nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. This project seeks to identify xenobiotics that can drive the progression of NAFLD and the molecular mechanisms behind each toxicity.

Results from this work will help to inform clinicians, drug companies and regulators regarding at-risk populations for xenobiotic toxicities.

Honor and Awards

  • NIH Pathway to Independence Award (K99/R00), NIEHS, 2015
  • Best Postdoctoral Publication Award, Postdoctoral Association, Society of Toxicology, 2015
  • 1st place Postdoctoral Poster Presentation Award, NIEHS Tamburro Symposium on Environmental Chemicals and Liver Disease, 2014
  • 1st place Postdoctoral Platform Award, Mountain West Chapter, Society of Toxicology, 2014
  • Gabriel L. Plaa Education Award 2nd place, Mechanisms Specialty Section, Society of Toxicology, 2014
  • Gabriel L. Plaa Education Award 1st place, Mechanisms Specialty Section, Society of Toxicology, 2013
  • Department of Defense Prostate Cancer Research Program Graduate Student Fellowship, 2009-2011
  • Student Interest Group Poster Presentation Finalist, American Society for Nutrition, Experimental Biology Conference, 2010
  • Dietary Bioactive Components Research Interest Group Poster Presentation Award Winner, American Society for Nutrition, Experimental Biology Conference, 2010 and 2011
  • Diet and Cancer Research Interest Group Poster Presentation Award Winner, American Society for Nutrition, Experimental Biology Conference, 2010 and 2011
  • Office of Dietary Supplements Practicum Travel Award Winner, Bethesda, Md., 2010
  • American Institute for Cancer Research Conference Travel Scholarship, 2008

Selected Publications
Clarke JD, Dzierlenga AL, Nelson NR, Li H, Werts S, Goedken MJ, Cherrington NJ.Mechanism of Altered Metformin Distribution in Nonalcoholic Steatohepatitis. Diabetes. 2015; 64(9):3305-13.

Clarke JD, Cherrington NJ. Nonalcoholic steatohepatitis in precision medicine: Unraveling the factors that contribute to individual variability. Pharmacology & therapeutics. 2015; 151:99-106.

Dzierlenga AL, Clarke JD, Hargraves TL, Ainslie GR, Vanderah TW, Paine MF, Cherrington NJ. Mechanistic basis of altered morphine disposition in nonalcoholic steatohepatitis. The Journal of pharmacology and experimental therapeutics. 2015; 352(3):462-70.

Canet MJ, Hardwick RN, Lake AD, Dzierlenga AL, Clarke JD, Goedken MJ, Cherrington NJ. Renal xenobiotic transporter expression is altered in multiple experimental models of nonalcoholic steatohepatitis. Drug metabolism and disposition: the biological fate of chemicals. 2015; 43(2):266-72.

Hardwick RN, Clarke JD, Lake AD, Canet MJ, Anumol T, Street SM, Merrell MD, Goedken MJ, Snyder SA, Cherrington NJ. Increased susceptibility to methotrexate-induced toxicity in nonalcoholic steatohepatitis. Toxicological sciences : an official journal of the Society of Toxicology. 2014; 142(1):45-55.

Clarke JD, Hardwick RN, Lake AD, Lickteig AJ, Goedken MJ, Klaassen CD, Cherrington NJ. Synergistic interaction between genetics and disease on pravastatin disposition. Journal of hepatology. 2014; 61(1):139-47.

Clarke JD, Sharapova T, Lake AD, Blomme E, Maher J, Cherrington NJ. Circulating microRNA 122 in the methionine and choline-deficient mouse model of non-alcoholic steatohepatitis. Journal of applied toxicology : JAT. 2014; 34(6):726-32.

Canet MJ, Hardwick RN, Lake AD, Dzierlenga AL, Clarke JD, Cherrington NJ. Modeling human nonalcoholic steatohepatitis-associated changes in drug transporter expression using experimental rodent models. Drug metabolism and disposition: the biological fate of chemicals. 2014; 42(4):586-95.

Merrell MD, Nyagode BA, Clarke JD, Cherrington NJ, Morgan ET. Selective and cytokine-dependent regulation of hepatic transporters and bile acid homeostasis during infectious colitis in mice. Drug metabolism and disposition: the biological fate of chemicals. 2014; 42(4):596-602.

Clarke JD, Hardwick RN, Lake AD, Canet MJ, Cherrington NJ. Experimental nonalcoholic steatohepatitis increases exposure to simvastatin hydroxy acid by decreasing hepatic organic anion transporting polypeptide expression. The Journal of pharmacology and experimental therapeutics. 2014; 348(3):452-8.

Clarke JD, Novak P, Lake AD, Shipkova P, Aranibar N, Robertson D, Severson PL, Reily MD, Futscher BW, Lehman-McKeeman LD, Cherrington NJ. Characterization of hepatocellular carcinoma related genes and metabolites in human nonalcoholic fatty liver disease. Digestive diseases and sciences. 2014; 59(2):365-74.

Meyer M, Kesic MJ, Clarke JD, Ho E, Simmen RC, Diaz-Sanchez D, Noah TL, Jaspers I. Sulforaphane induces SLPI secretion in the nasal mucosa. Respiratory medicine. 2013; 107(3):472-5.

Clarke JD, Cherrington NJ. Genetics or environment in drug transport: the case of organic anion transporting polypeptides and adverse drug reactions. Expert opinion on drug metabolism & toxicology. 2012; 8(3):349-60.

Clarke JD, Hsu A, Williams DE, Dashwood RH, Stevens JF, Yamamoto M, Ho E. Metabolism and tissue distribution of sulforaphane in Nrf2 knockout and wild-type mice. Pharmaceutical research. 2011; 28(12):3171-9.

Clarke JD, Hsu A, Riedl K, Bella D, Schwartz SJ, Stevens JF, Ho E. Bioavailability and inter-conversion of sulforaphane and erucin in human subjects consuming broccoli sprouts or broccoli supplement in a cross-over study design. Pharmacological research. 2011; 64(5):456-63.

Clarke JD, Riedl K, Bella D, Schwartz SJ, Stevens JF, Ho E. Comparison of isothiocyanate metabolite levels and histone deacetylase activity in human subjects consuming broccoli sprouts or broccoli supplement. Journal of agricultural and food chemistry. 2011; 59(20):10955-63.

Clarke JD, Hsu A, Yu Z, Dashwood RH, Ho E. Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal prostate cells versus hyperplastic and cancerous prostate cells. Molecular nutrition & food research. 2011; 55(7):999-1009.

Ho E, Clarke JD, Dashwood RH. Dietary sulforaphane, a histone deacetylase inhibitor for cancer prevention. The Journal of nutrition. 2009; 139(12):2393-6.

Clarke JD, Dashwood RH, Ho E. Multi-targeted prevention of cancer by sulforaphane. Cancer letters. 2008; 269(2):291-304.

updated 09/14/2016 Back to top
John D. Clarke

Assistant Professor
Pharmaceutical Sciences

j.clarke@wsu.edu
Office: 509-358-7929
Lab: 509-368-6543
PBS 345

P.O. Box 1495
Washington State University
Spokane, WA  99210-1495