Dr. Robert Andrew Roth

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Michigan State University
College of Veterinary Medicine
Pharmacology and Toxicology
ProfessorAppointed: 1987
Michigan State University
National Food Safety and Toxicology Center
Toxicology Research
Associate DirectorAppointed: 1995
Professional Headshot of Robert Andrew Roth

Mailing Address

B346 Life Science Bldg.
Department of Pharmacology/Toxicology
Michigan State University
East Lansing, Michigan 48824
United States

Contact Information

Phone: (517) 432-2310
Fax: (517) 432-2310
rothr@msu.edu

Qualifications

Postdoctoral, Yale University, Pulmonary Pharmacology, 1977.
Ph.D., Johns Hopkins University, Biochemical Toxicology, 1975.
B.A., Duke University, Chemistry, 1968.

Expertise and Research Interests

Drug idiosyncrasy
Liver injury and toxicology
Mechanisms by which neutrophils, platelets, hemostasis, hypoxia and soluble mediators of inflammation (e.g., thrombin) influence hepatotoxic responses to chemicals
Bacterial endotoxin exposure as a determinant of susceptibility to foodborne chemicals
Mechanisms of neutrophil-dependent hepatocellular killing

Other Expertise

Member, Editorial Board, 'Toxicology and Applied Pharmacology', 1993-present

Member, Editorial Board, 'Journal of Toxicology and Environmental Health', 1985-present

Member, Environmental Health Sciences Review Committee, NIEHS, 1994-1999

Member, Board of Publications, Society of Toxicology, 1998-2003; Chair, 1999-2001

Member, Board of Directors, American Board of Toxicology, 1998-2003

President, Food Safety Specialty Section, Society of Toxicology, 2001-2002

Assoc. Editor, Journalof Pharmacology and Experimental Therapeutics, 2002-present

Industrial Relevance

Adverse drug responses occur in people, and these often bear no obvious relationship to drug dose or treatment regimen. These idiosyncratic reactions are not well understood. We are intrigued by the possibility that some people may be more sensitive toadverse drug responses when they have modest, concurrent infammatory responses. Our studies demonstrating that modest inflammation induced by LPS can enhance hepatotoxicity and prompt the emergence of new target tissues has raised our interest in this possibility and may provide a new paradigm for understanding drug idiosyncrasy and developing predictive animal and in vitro models.

Keywords

COS Keywords:

Environment (Health Or Safety Or Medical), Environmental Chemistry, Environmental Health, Environmental Medicine, Food Safety, Growth Factors, Inflammation, Pharmacology, Toxicology.

Additional Terms:

Adverse Drug Reaction, Alcohol, Coagulation, Endotoxin, Fibrinolysis, Food Safety, Functional Food, Hemostasis, Hepatic, Hepatocyte, Hepatotoxicity, Hypoxia, Idiosyncrasy, Inflammation, Liver, Monocrotaline, Monocrotaline Pyrrole, Neutrophil, Nutritional Supplement, Plant Toxins, Platelets, Pyrrolizidine Alkaloid, Superoxide Dismutase, Thrombin, Toxicity, Toxicology.

Memberships

American Association for the Advancement of Science
American Society for Pharmacology and Experimental Therapeutics
International Society for the Study of Xenobiotics
International Union of Pharmacology
Society of Toxicology

Honors and Awards

2001, Kenneth DuBois Achievement in Toxicology Award, Midwest Regional Chapter of the Society of Toxicology
1992, Distinguished Faculty Award, Michigan State University
1991-1996, Burroughs-Wellcome Scholar in Toxicology,

Previous Positions

1982-1987, Associate Professor, Michigan State University, Pharmacology and Toxicology and Institute for Environmental Toxicology
1977-1982, Assistant Professor, Michigan State University, Pharmacology and Toxicology and the Institute for Environmental Toxicology

Funding Received

  • National Institutes of Health (NIH): Inflammation and Drug Idiosyncrasy, Oct 1, 2003 to Sep 30, 2007.
  • National Institutes of Health (NIH): Distal Events in the Hepatotoxicity of Endotoxin, Aug 1, 1996 to Jul 31, 2001.
  • National Institutes of Health (NIH): Neutrophils and Hepatotoxicity, Apr 1, 1998 to Mar 31, 2003.

Publications

  • Luyendyk JP, Mattes WB, Burgoon LD, Zacharewski TR, Maddox JF, Cosma GN, Ganey PE, Roth RA, Gene expression analysis points to hemostasis in livers of rats cotreated with lipopolysaccharide and ranitidine, Toxicological Sciences : an Official Journal of the Society of Toxicology., 80(1), 203-13, July 2004 Abstract
  • Willett KL, Roth RA, Walker L, Workshop overview: Hepatotoxicity assessment for botanical dietary supplements, Toxicological Sciences : an Official Journal of the Society of Toxicology., 79(1), 4-9, May 2004 Abstract
  • Harrigan GG, LaPlante RH, Cosma GN, Cockerell G, Goodacre R, Maddox JF, Luyendyk JP, Ganey PE, Roth RA, Application of high-throughput Fourier-transform infrared spectroscopy in toxicology studies: contribution to a study on the development of an animal model for idiosyncratic toxicity, Toxicology Letters, 146(3), 197-205, February 2004 Abstract
  • Maddox JF, Domzalski AC, Roth RA, Ganey PE, 15-deoxy prostaglandin J2 enhances allyl alcohol-induced toxicity in rat hepatocytes, Toxicological Sciences : an Official Journal of the Society of Toxicology., 77(2), 290-8, February 2004 Abstract
  • Copple BL, Rondelli CM, Maddox JF, Hoglen NC, Ganey PE, Roth RA, Modes of cell death in rat liver after monocrotaline exposure, Toxicological Sciences : an Official Journal of the Society of Toxicology., 77(1), 172-82, January 2004 Abstract
  • Ganey, P.E., Barton, Y.-W., Kinser, S., Sneed, R.A., Barton, C.C., and Roth, R.A., Involvement of cyclooxygenase-2 in the potentiation of allyl alcohol-induced liver injury by bacterial lipopolysaccharide, Toxicology and Applied Pharmacology, 174, 113-121, 2001
  • Zhou HR, Harkema JR, Hotchkiss JA, Yan D, Roth RA, Pestka JJ, Lipopolysaccharide and the trichothecene vomitoxin \(deoxynivalenol\) synergistically induce apoptosis in murine lymphoid organs., Toxicological Sciences, 53(2), 253-63, 2000 Abstract
  • Rumbeiha, W.K., Fitzgerald, S.K. Braselton, W.E., Roth, R.A. and Kaneene, J.B., Potentiation of mercury-induced nephrotoxicity by endotoxin in the Sprague-Dawley rat, Toxicology, 149, 75-87, 2000
  • Rumbeiha, W.K., Fitzgerald, S.K., Braselton, W.E., Roth, R.A., Pestka, J.J. and Kaneene, J.B., Augmentation of mercury-induced nephrotoxicity by endotoxin in the mouse, Toxicology, 150, 103-116, 2000
  • Yee, S.B., Kinser, S., Hill, D.A., Barton, C.C., Hotchkiss, J.A., Harkema, J.R., Ganey, P.E. and Roth, R.A., Synergistic hepatotoxicity from coexposure to bacterial endotoxin and the pyrrolizidine alkaloid monocrotaline. Toxicol. Appl. Pharmcol, 166, 173-185, 2000
  • Barton, C.C., Ganey P.E. and Roth, R.A., Lipopolysaccharide augments aflatoxin B1-induced liver injury through neutrophil-dependent and -independent mechanisms, Toxicological Sciences, 58, 208-215, 2000
  • Barton, C.C., Barton, E.X., Ganey, P.E., Kunkel, S.L. and Roth, R.A., Expression of tumor necrosis factor-alpha underlies increased susceptibility to aflatoxin B1 toxicity after lipopolysaccharide exposure, Hepatology, 33, 66-73, 2000
  • Wagner JG, Roth RA, Neutrophil migration during endotoxemia., Journal of Leukocyte Biology, 66(1), 10-24, July 1999 Abstract
  • Hill DA, Jean PA, Roth RA, Bile duct epithelial cells exposed to alpha-naphthylisothiocyanate produce a factor that causes neutrophil-dependent hepatocellular injury in vitro, Toxicological Sciences, 47(1), 118-25, Jan 1999 Abstract
  • Hill DA, Jean PA, Roth RA, Bile duct epithelial cells exposed to alpha-naphthylisothiocyanate produce a factor that causes neutrophil-dependent hepatocellular injury in vitro., Toxicological Sciences, 47(1), 118-25, Jan 1999 Abstract
  • Lappin PB, Ross KL, King LE, Fraker PJ, Roth RA, The response of pulmonary vascular endothelial cells to monocrotaline pyrrole: cell proliferation and DNA synthesis in vitro and in vivo., Toxicology and Applied Pharmacology, 150(1), 37-48, 1998 Abstract
  • Molnar RG, Wang P, Ayala A, Ganey PE, Roth RA, Chaudry IH, The role of neutrophils in producing hepatocellular dysfunction during the hyperdynamic stage of sepsis in rats., Journal of Surgical Research, 73(2), 117-22, December 1997 Abstract
  • Pearson JM, Bailie MB, Fink GD, Roth RA, Neither platelet activating factor nor leukotrienes are critical mediators of liver injury after lipopolysaccharide administration, Toxicology, 121(3), 181-9, September 1997 Abstract
  • Roth RA, Dahm LJ, Neutrophil- and glutathione-mediated hepatotoxicity of alpha-naphthylisothiocyanate, Drug Metabolism Reviews, 29(1-2), 153-65, 1997 Abstract
  • Moulin F, Pearson JM, Schultze AE, Scott MA, Schwartz KA, Davis JM, Ganey PE, Roth RA, Thrombin is a distal mediator of lipopolysaccharide-induced liver injury in the rat, Journal of Surgical Research, 65(2), 149-58, October 1996 Abstract
  • Wagner JG, Ganey PE, Roth RA, Nitric oxide is not involved in hepatocyte killing by neutrophils activated by N-formyl-methionyl-leucylphenylalanine or phorbol myristate acetate in vitro, Hepatology, 23(4), 803-10, April 1996 Abstract
  • Bailie MB, Pearson JM, Fink GD, Roth RA, Platelet activating factor receptor blockade alone or in combination with leukotriene synthesis inhibition does not ameliorate alpha-naphthylisothiocyanate-induced hepatotoxicity, Toxicology Letters, 84(2), 89-95, February 1996 Abstract
  • Jean PA, Roth RA, Naphthylisothiocyanate disposition in bile and its relationship to liver glutathione and toxicity., Biochemical Pharmacology, 50(9), 1469-74, 26 Oct 1995 Abstract
  • Bailie MB, Jean PA, Lappin PB, Scozzaro MJ, Schmidt TM, Moulin FJ, Roth RA, Vitamin A or zymosan pretreatment attenuates alpha-naphthylisothiocyanate-induced liver injury, Toxicology and Applied Pharmacology, 134(1), 63-70, September 1995 Abstract
  • Bailie MB, Dahm LJ, Peters-Golden M, Harris RR, Carter GW, Roth RA, Leukotrienes and alpha-naphthylisothiocyanate-induced liver injury, Toxicology, 100(1-3), 139-49, June 1995 Abstract
  • Jean PA, Bailie MB, Roth RA, 1-naphthylisothiocyanate-induced elevation of biliary glutathione., Biochemical Pharmacology, 49(2), 197-202, 18 1995 Abstract
  • Hewett JA, Roth RA, The coagulation system, but not circulating fibrinogen, contributes to liver injury in rats exposed to lipopolysaccharide from gram-negative bacteria, Journal of Pharmacology and Experimental Therapeutics, 272(1), 53-62, January 1995 Abstract
  • Hoorn CM, Wagner JG, Petry TW, Roth RA, Toxicity of mitomycin C toward cultured pulmonary artery endothelium, Toxicology and Applied Pharmacology, 130(1), 87-94, January 1995 Abstract
  • Bailie MB, Pearson JM, Lappin PB, Killam AL, Roth RA, Platelets and alpha-naphthylisothiocyanate-induced liver injury, Toxicology and Applied Pharmacology, 129(2), 207-13, December 1994 Abstract
  • Schultze AE, Gunaga KP, Wagner JG, Hoorn CM, Moorehead WR, Roth RA, Lactate dehydrogenase activity and isozyme patterns in tissues and bronchoalveolar lavage fluid from rats treated with monocrotaline pyrrole, Toxicology and Applied Pharmacology, 126(2), 301-10, June 1994 Abstract
  • Bailie MB, Hewett JA, Schultze AE, Roth RA, Methylene dianiline hepatotoxicity is not leukocyte-dependent, Toxicology and Applied Pharmacology, 124(1), 25-30, January 1994 Abstract
  • Ganey PE, Bailie MB, VanCise S, Colligan ME, Madhukar BV, Robinson JP, Roth RA, Activated neutrophils from rat injured isolated hepatocytes, Laboratory Investigation, 70(1), 53-60, January 1994 Abstract
  • Hewett JA, Roth RA, Hepatic and extrahepatic pathobiology of bacterial lipopolysaccharides, Pharmacological Reviews, 45(4), 382-411, December 1993 Abstract
  • Hoorn CM, Roth RA, Monocrotaline pyrrole-induced changes in angiotensin-converting enzyme activity of cultured pulmonary artery endothelial cells, British Journal of Pharmacology, 110(2), 597-602, October 1993 Abstract
  • Ganey PE, Sirois JE, Denison M, Robinson JP, Roth RA, Neutrophil function after exposure to polychlorinated biphenyls in vitro, Environmental Health Perspectives, 101(5), 430-4, October 1993 Abstract
  • Schultze AE, Roth RA, Procoagulant and fibrinolytic properties of bovine endothelial cells treated with monocrotaline pyrrole, Toxicology and Applied Pharmacology, 122(1), 7-15, September 1993 Abstract
  • Schultze AE, Roth RA, Fibrinolytic activity in blood and lungs of rats treated with monocrotaline pyrrole, Toxicology and Applied Pharmacology, 121(1), 129-37, July 1993 Abstract
  • Hoorn CM, Wagner JG, Roth RA, Effects of monocrotaline pyrrole on cultured rat pulmonary endothelium, Toxicology and Applied Pharmacology, 120(2), 281-7, June 1993 Abstract
  • Bailie MB, Mullaney TP, Roth RA, Characterization of acute 4,4'-methylene dianiline hepatotoxicity in the rat, Environmental Health Perspectives, 101(2), 130-3, June 1993 Abstract
  • Bailie MB, Roth RA, Contreras ML, Nerve growth factor binding sites on hepatic parenchymal cells, In Vitro Cellular and Developmental Biology, 28A(9-10), 621-4, 1992 Abstract
  • Hoorn CM, Roth RA, Monocrotaline pyrrole alters DNA, RNA and protein synthesis in pulmonary artery endothelial cells, American Journal of Physiology, 262(6 Pt 1), L740-7, June 1992 Abstract
  • Hewett JA, Schultze AE, VanCise S, Roth RA, Neutrophil depletion protects against liver injury from bacterial endotoxin, Laboratory Investigation, 66(3), 347-61, March 1992 Abstract
  • Reindel JF, Hoorn CM, Wagner JG, Roth RA, Comparison of response of bovine and porcine pulmonary arterial endothelial cells to monocrotaline pyrrole, American Journal of Physiology, 261(6 Pt 1), L406-14, December 1991 Abstract
  • Schultze AE, Wagner JG, White SM, Roth RA, Early indications of monocrotaline pyrrole-induced lung injury in rats, Toxicology and Applied Pharmacology, 109(1), 41-50, June 1991 Abstract
  • Reindel JF, Roth RA, The effects of monocrotaline pyrrole on cultured bovine pulmonary artery endothelial and smooth muscle cells, American Journal of Pathology, 138(3), 707-19, March 1991 Abstract
  • Reindel JF, Ganey PE, Wagner JG, Slocombe RF, Roth RA, Development of morphologic, hemodynamic, and biochemical changes in lungs of rats given monocrotaline pyrrole, Toxicology and Applied Pharmacology, 106(2), 179-200, November 1990 Abstract
  • Ahmadizadeh M, Echt R, Heusner WW, Ross LM, Roth RA, Effect of carbon tetrachloride on hamster tracheal epithelial cells, Journal of Toxicology and Environmental Health, 30(4), 273-85, August 1990 Abstract
  • Dahm LJ, Roth RA, Differential effects of lithocholate on rat neutrophil activation, Journal of Leukocyte Biology, 47(6), 551-60, June 1990 Abstract
  • Roth RA, Hewett JA, The cholestatic agent, alpha-naphthylisothiocyanate, stimulates superoxide release by rat neutrophils in vitro, Laboratory Investigation, 62(6), 736-41, June 1990 Abstract
  • Barton, C.C., Barton, E.X., Ganey, P.E., Kunkel, S.L. and Roth, R.A., Expression of tumor necrosis factor-alpha underlies increased susceptibility to aflatoxin B1 toxicity after lipopolysaccharide exposure, Hepatology 33: 66-73, 2001.
  • Barton, C.C., Ganey P.E. and Roth, R.A., Lipopolysaccharide augments aflatoxin B1-induced liver injury through neutrophil-dependent and -independent mechanisms, Toxicol. Sci. 58(1): 208-215, 2000.
  • Buchweitz, J.P., Ganey, P.E., Bursian, S.J. and Roth, R.A., Underlying endotoxemia augments toxic responses to chlorpromazine: Is there a relationship to drug idiosyncrasy?, J. Pharmacol. Exp. Ther. 300(2): 460-467, 2001.
  • Moulin, F., Copple, B.L., Ganey, P.E. and Roth, R.A., Hepatic and extrahepatic factors critical for liver injury during lipopolysaccharide exposure, Amer. J. Physiol. 281(6): G1423-G1431, 2001.
  • Copple, B.L., Banes, A., Ganey, P.E. and Roth, R.A., Endothelial cell injury and fibrin deposition in rat liver after monocrotaline exposure, Toxicol. Sci. 65(2): 309-318, 2002.
  • Wagner, J.G., Harkema, J.R. and Roth, R.A.:, Pulmonary leukostasis and the inhibition of airway neutrophil recruitment are early events in the endotoxemic rat, Shock 17: 151-158, 2002.
  • Copple, B.L., Woolley, B., Banes, A., Ganey, P.E. and Roth, R.A., Anticoagulants prevent monocrotaline-induced hepatic parenchymal cell injury but not endothelial cell injury in the rat, Toxicol. Appl. Pharmacol. 180: 186-196, 2002.
  • Luyendyk, J.P., Shores, K.A., Ganey, P.E. and Roth, R.A., Bacterial lipopolysaccharide exposure alters aflatoxin B1 hepatotoxicity: Benchmark dose analysis for markers of liver injury, Toxicol. Sci. 68: 220-225, 2002.
  • Kinser, S., Roth, R.A. and Ganey, P.E., Enhancement of allyl alcohol hepatotoxicity by endotoxin requires extrahepatic factors, Toxicol. Sci. 69: 470-481, 2002.
  • Yee, S.B., Ganey, P.E. and Roth, R.A., The role of Kupffer cells and TNF-alpha in monocrotaline and bacterial lipopolysaccharide-induced liver injury, Toxicol. Sci. 71: 124-132, 2002.
  • Luyendyk, J.P., Copple, B.L., Barton, C.C., Ganey, P.E. and Roth, R.A., Augmentation of aflatoxin B1 hepatotoxicity by endotoxin: involvement of endothelium and the coagulation system, Toxicol. Sci. 72: 171-181, 2003.
  • Copple, B.L., Moulin, F., Hanumegowda, U., Ganey, P.E. and Roth, R.A., Thrombin and protease-activated receptor-1 agonists promote lipopolysaccharide-induced hepatocellular injury in perfused livers, J. Pharmacol. Exp. Ther. 305: 417-425, 2003.
  • Yee, S.B., Hanumegowda, U.M., Hotchkiss, J.A., Ganey, P.E. and Roth, R.A., Role of neutrophils in the synergistic liver injury from monocrotaline and bacterial lipopolysaccharide exposure, Toxicol. Sci. 72: 43-56. 2003.
  • Maddox, J.F., Roth, R.A., and Ganey, P.E.:, Allyl alcohol activation of protein kinase C leads to cytotoxicity of rat hepatocytes, Chem. Res. Toxicol., in press, 2003.

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Last Updated: 10/28/2005

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