John Clarke

Associate Professor, Pharmaceutical Sciences j.clarke@wsu.edu 509-358-7929 PBS 343 Spokane https://labs.wsu.edu/johnclarke/

Education

PhD in molecular and cellular biology, Oregon State University, Corvallis, Oregon
Bachelor of Science in biology, Brigham Young University-Idaho, Rexburg, Idaho

About Me

Growing up in western Washington, I always wanted to be a teacher. I eventually decided I wanted to teach high school biology and coach sports. It was not until my junior year of college that I discovered my passion for research and decided to earn a PhD. Now, I fulfill my passion for teaching and research as a faculty member in the College of Pharmacy and Pharmaceutical Sciences. I teach in the Principles of Pharmacology and Fundamental of Toxicology course in the Pharmaceutical Sciences and Molecular Medicine PhD program and in the Integrated Pharmacology II course in the Doctor of Pharmacy (PharmD) program. Mentoring PhD and PharmD students in my research lab is a highlight of my work.

My research group focuses on understanding inter-individual variability in xenobiotic exposures and toxicities—meaning, we want to know what makes two people different in terms of how they handle and react to toxins and drugs. Some of the variables we research that make two people different include genetics, diseases, and dietary supplement use. We study each of these variables both alone and in combination with each other. We have particular expertise in drug transporters and liver diseases, such as nonalcoholic fatty liver disease. Our research can be summarized in one major goal: improve precision medicine by accounting for the factors in inter-individual variability.

In my spare time I like to…

I enjoy spending time with my family hiking, running, biking, boating, and camping.

Grants/Awards

R00ES024455
04/01/2017 – 03/31/2021 (NCE)
Clarke (PI)

Title: Microcystin-LR toxicity in nonalcoholic steatohepatitis

Goal: Investigate how the liver disease nonalcoholic steatohepatitis affects the toxicity of microcystin-LR (an environmental toxin from blue-green algae) and how the toxin is removed from the body.

R21AT011101
08/01/2020 – 07/31/2022
Clarke (PI)

Title: Enteric and hepatic transporter mechanisms for pharmacokinetic natural product-drug interactions.

Goal: Determine how the natural product-drug interactions between goldenseal-metformin and green tea-raloxifene are affecting how the intestine and liver handle drugs in the body.

R56AT010650
09/23/2020 – 09/22/2021
Clarke (PI)

Title: Risk of xenobiotic-drug interactions in chronic disease

Goal: Determine the individual and combined effects of the natural product silymarin (often marketed for liver disease) and the liver disease nonalcoholic steatohepatitis (NASH) on how the liver removes drugs from the body.

1R01ES032558
1/19/2020 – 10/31/2025
Clarke (PI)

Title: Mechanisms of microcystin-induced hepatocellular carcinoma in nonalcoholic Steatohepatitis

Goal: Investigate how microcystin-LR causes liver cancer in nonalcoholic steatohepatitis (NASH).

Selected Publications

Montonye ML, Tian DD, Arman T, Lynch KD, Hagenbuch B, Paine MF, Clarke JD. A Pharmacokinetic Natural Product-Disease-Drug Interaction: A Double Hit of Silymarin and Nonalcoholic Steatohepatitis on Hepatic Transporters in a Rat Model. J Pharmacol Exp Ther. 2019 Nov;371(2):385-393. doi: 10.1124/jpet.119.260489. Epub 2019 Aug 16. PubMed PMID: 31420525; PubMed Central PMCID: PMC6800447.

Arman T, Lynch KD, Montonye ML, Goedken M, Clarke JD. Sub-Chronic Microcystin-LR Liver Toxicity in Preexisting Diet-Induced Nonalcoholic Steatohepatitis in Rats. Toxins (Basel). 2019 Jul 9;11(7). doi: 10.3390/toxins11070398. PubMed PMID: 31323923; PubMed Central PMCID: PMC6669744.

Clarke JD, Novak P, Lake AD, Hardwick RN, Cherrington NJ. Impaired N-linked glycosylation of uptake and efflux transporters in human non-alcoholic fatty liver disease. Liver Int. 2017 Jul;37(7):1074-1081. doi: 10.1111/liv.13362. Epub 2017 Feb 7. PubMed PMID: 28097795; PubMed Central PMCID: PMC5479731.

Dzierlenga AL, Clarke JD, Klein DM, Anumol T, Snyder SA, Li H, Cherrington NJ. Biliary Elimination of Pemetrexed Is Dependent on Mrp2 in Rats: Potential Mechanism of Variable Response in Nonalcoholic Steatohepatitis. J Pharmacol Exp Ther. 2016 Aug;358(2):246-53. doi: 10.1124/jpet.116.234310. Epub 2016 May 27. PubMed PMID: 27233293; PubMed Central PMCID: PMC4959105.

Clarke JD, Dzierlenga AL, Nelson NR, Li H, Werts S, Goedken MJ, Cherrington NJ. Mechanism of Altered Metformin Distribution in Nonalcoholic Steatohepatitis. Diabetes. 2015 Sep;64(9):3305-13. doi: 10.2337/db14-1947. Epub 2015 May 27. PubMed PMID: 26016715; PubMed Central PMCID: PMC4542448.

Clarke JD, Cherrington NJ. Nonalcoholic steatohepatitis in precision medicine: Unraveling the factors that contribute to individual variability. Pharmacol Ther. 2015 Jul;151:99-106. doi: 10.1016/j.pharmthera.2015.03.005. Epub 2015 Mar 21. Review. PubMed PMID: 25805597; PubMed Central PMCID: PMC4457694.

Clarke JD, Hardwick RN, Lake AD, Lickteig AJ, Goedken MJ, Klaassen CD, Cherrington NJ. Synergistic interaction between genetics and disease on pravastatin disposition. J Hepatol. 2014 Jul;61(1):139-47. doi: 10.1016/j.jhep.2014.02.021. Epub 2014 Mar 5. PubMed PMID: 24613363; PubMed Central PMCID: PMC4065643.

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. Dig Dis Sci. 2014 Feb;59(2):365-74. doi: 10.1007/s10620-013-2873-9. Epub 2013 Sep 19. PubMed PMID: 24048683; PubMed Central PMCID: PMC3945102.

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. Pharmacol Res. 2011 Nov;64(5):456-63. doi: 10.1016/j.phrs.2011.07.005. Epub 2011 Jul 26. PubMed PMID: 21816223; PubMed Central PMCID: PMC3183106.

Ho E, Clarke JD, Dashwood RH. Dietary sulforaphane, a histone deacetylase inhibitor for cancer prevention. J Nutr. 2009 Dec;139(12):2393-6. doi: 10.3945/jn.109.113332. Epub 2009 Oct 7. PubMed PMID: 19812222; PubMed Central PMCID: PMC2777483.