John M. Clark

Professor

I am a pesticide toxicologist with 40+ years’ professional experience and expertise in the fields of human exposure to pesticides, pesticide mode of action and molecular elucidation of resistance mechanisms. I have extensive experience studying the modes of action of pyrethroid, organophosphorus, carbamate, organochlorine, phenylpyrazole and macrocyclic lactone insecticides.

My research group has studied the neurotoxicology of insecticides, primarily dealing with Ca²⁺-dependent neurotransmitter release and voltage sensitive Ca²⁺-channels, in rat brain tissues for some 25+ years using a variety of biochemical approaches and techniques including: agonists/antagonists, radioisotopes, fluorescent probes, electrophysiology and functional and reverse genetics. We have studied the mechanisms of insecticide resistance in a variety of blood-sucking insect that vector disease and have used functional genomics to develop DNA-based diagnostics to monitor the evolution of resistance in vector populations.

Current Research
My research group, along with collaborators, are studying: (1) the role of insecticides in the increase occurrence of childhood obesity and type 2 diabetes; (2) the mode of action/resistance of a number of new insecticides for the control of human ectoparasites (e.g., lice, bed bugs and mosquitoes) and the development of sustainable resistance management strategies; (3) the effect of neurotoxicants on native channels and receptors expressed in neurolemma fragments injected into Xenopus laevis oocytes as a high-throughput screen to identify novel target sites; (4) the role of the innate immune response in the evolution of vector competence in human lice and (5) PFAS disruption of receptor-mediated endocytosis and later life metabolic dysfunction.

Learn more at www.vasci.umass.edu/research-faculty/john-marshall-clark

Academic Background

BS Zoology, Univ. of Wisconsin-Madison, 1972
MS Entomology (Insecticide Toxicology), Univ. of Wisconsin-Madison, 1977
PhD Toxicology, Michigan State University, 1981

Selected Publications

Qi, W., Clark, J.M. Suvorov, A. Park, Y. 2019. Ivermectin decreases triglyceride accumulation by inhibiting adipogenesis of 3T3-L1 preadipocytes. Food and Chem. Toxicol. 131:1-10,

https://doi.org/10.1016/j.fet.2019.110576

Clark, J.M. Chapter 6. New developments in the control of human lice. Wiley-VCH, In Drug Discovery in Infectious Disease: Volume 6- Ectoparasites: Drug Discovery Against Moving Targets, Eds. C. Meng and A. Sluder. 2018 pp. 119-137.

Kim, J.H., Gellatly, K.J., Lueke, B., Kohler, M., Nauen, R., Murenzi, E., Yoon, K.S., Clark, J.M. 2018. Detoxification of ivermectin by ATP binding cassette transporter C4 and cytochrome P450 monooxygenase 6CJ1 in the human body louse, Pediculus humanus humanus. Pestic. Biochem. Physiol. 27:73-82.

http://dx.doi.org/10.1111/imb.12348.

Qi, W., Clark, J.M., Timme-Laragy, A., Park, Y. 2018. Perfluorobutanesulfonic acis (PFBS) potentiates adipogenesis of 3T3-L1 adipocytes. Food and Chem. Toxicol. 120:340-345.

Yang, J.S., Symington, S.B., Clark, J.M. Park, Y. 2018. Permethrin, a pyrethroid insecticides, regulates ERK1/2 activation through membrane depolarization-mediated pathway in HepG2 hepatocytes. Food and Chem. Toxicol. 121:387-395.

Symington, S.B. Murenzi, E., Toltin, A.C., Lansky, D. and Clark, J.M. Realizing the Potential: Improving a Microtransplantation Assay based on Neurolemma-injected Xenopus Oocytes. In Advances in Agrochemicals: Ion Channels and G-protein coupled Receptors (GPCR) as Targets for Pest Control. Eds. Gross et al., ACS Symposiun Series Vol. 1264, ACS Books, Washington D.C. DOI.10.1021/bk-2017-2164.ch004. 2017 pp. 53-73.

http://dx.doi.org/10.1021/bk-2017-2164.ch004

Shen, P., Hsieh, T-H., Yue, Y., Sun, Q, Clark, J.M., Park, Y. 2017. Deltamethrin increases the fat accumulation in 3T3-L1 adipocytes and Caenorhabditis elegans. Food and Chemical Toxicology. 101: 149-156.

http://Doi.org/10.1016/j.fct.2017.01.015

Xiao, X., W. Qi, J. M. Clark, and Y. Park. 2017. Permethrin potentiates adipogenesis via intracellular calcium and endoplasmic reticulum stress-mediated mechanisms in 3T3-L1 adipocytes. Food Chem. Toxicol. 109: 123-129.

Kim, J. H., D. J. Previte, K. S. Yoon, E. Murenzi, J. E. Koehler, B. R. Pittendrigh, S. H. Lee, and J. M. Clark. 2017. Comparison of the proliferation and excretion of Bartonella quintana between body and head lice following oral challenge. Insect Mol. Biol. 26: 266-276.

Sun, Q., Qi, W., Yang, J.J., Yoon, K.S., Clark, J.M., Park, Y. 2016. Fipronil promotes adipogenesis via AMPKα-mediated pathway in 3T3-L1 adipocytes. Food and Chem. Toxicol. http://dxdoi.org/ 10.1016/j.fct.2016.04.011

Kim, J., Park, Y., Yoon, K.S., Clark, J.M., Park, Y. 2014. Permethrin alters adipogenesis in 3T3-L1 adipocytes and causes insulin resistance in C2C12 myotubes. J. Biochem. Mol. Toxicol. 28:418-424. PMID: 24911977

Abromaitis S., Nelson, C.S., Previte, D., Yoon, K.S., Clark, J.M., DeRisi, J.L., Koehler J.E. 2013 Bartonella quintana deploys host and vector temperature-specific transcriptomes, PLOS ONE 8:e58773. PMC3595295

Previte, D.J., Olds, B.P., Yoon, K.S., Sun, W., Muir, B., Paige, K.N., Lee, S.H., Clark, J.M. Koehler, J.E., Pittendrigh, B.R., Clark, J.M. 2013. Differential gene expression in human head and body lice when challenged with Bartonella quintana, a pathogenic bacterium. Insect Molecular Biol. 23:244-254. PMC4454818

Park, Y., Kim, Y., Kim, J., Yoon, K.S., Clark, J.M., Lee. J., Park, Y. 2013. Imidacloprid, a neonicotinoid insecticide, potentiates adipogenesis in 3T3-L1 adipocytes. J. Agric. Food. Chem. 61:255-259. PMID: 23215241.

Kirkness, E.F., ...Clark, J.M. (6th of 72) et al. (The Human Body Louse Genome Consortium Group). 2010. Genome sequences of the human body louse and its endosymbiont provide insights into the permanent parasitic lifestyle. PNAS, 107:12168-12173. PMC2901460

Breckenridge, C., Holden, L., Nemec, M. Weiner, M., Sheets, L., Sargent, D., Choi, J-S., Soderlund, D.M, Symington, S.B., Clark, J.M, Burr, S., and D. Ray. 2009. Evidence for separate mechanisms of action of type I and type II pyrethroid insecticides. Neurotoxicology, 30:17-31. PMID: 19766671.

Yoon, K.S., Symington, S.B., Lee, S.-H., Soderlund, D.M. and Clark, J.M.2008. Three Mutations Identified in the Voltage-sensitive Sodium Channel alpha-subunit Gene of Permethrin-resistant Human Head Lice Abolish Permethrin Sensitivity of the House Fly Vssc1 Expressed in Xenopus Oocytes. Insect. Biochem. & Mol. Biol. 38:296-306. PMC2329913

Soderlund, D.M., Clark, J.M. et al. Mechanisms of Pyrethroid Neurotoxicity; Implications for Cumulative Risk Assessment. Toxicology. 2002. 171:3-59. PMID: 11812616

John M. Clark

Institute for Applied Life Sciences