Patricia Ganey, Ph.D.
- Hepatic Faculty, Immunopharmacology Faculty
Professor, Pharmacology & Toxicology
Dr. Patricia Ganey
214 Food Safety Toxicology
1129 Farm Lane
East Lansing, MI 48824
Fields of Interest: Dr. Ganey’s research focuses on understanding mechanisms by which inflammation modulates responses to chemicals. Of particular interest are chemicals, including drugs, that damage liver.
- 1979 - B.S., Biological Sciences, University of Maryland
- 1986 - Ph.D., Pharmacology—Environmental Toxicology, Michigan State University
- 1986-1989 - Postdoctoral Fellow, University of North Carolina at Chapel Hill
- 1990-1996 - Assistant Professor, Medicine, Michigan State University
- 1996-1998 - Assistant Professor, Pharmacology and Toxicology, Michigan State University
- 1998-2006 - Associate Professor, Pharmacology and Toxicology, Michigan State University
- 2006-present - Professor, Pharmacology and Toxicology, Michigan State University
Inflammation/chemical interaction and toxicity: The primary focus of our research is to understand the mechanisms and consequences of interactions between the inflammatory response and chemicals that lead to toxicity. The chemicals of interest range from environmental chemicals to drugs, and the target of interest is the liver.
One project involves inflammation/drug interaction that leads to liver injury in experimental animals. These responses mimic idiosyncratic, adverse drug responses that occur in people. Idiosyncratic responses occur in a very small fraction of people, and dose-response relationships are not obvious. The mechanisms underlying these reactions are unknown. Liver is a frequent target, and some of the more serious idiosyncratic reactions in liver can lead to the necessity of liver transplantation or even death.
A problem with understanding these reactions is the lack of animal models that mimic the response. We have found that for many drugs this type of adverse reaction can be reproduced in experimental animals by cotreatment with drug and an agent to induce inflammation. We are using these animal models to explore mechanisms of hepatotoxicity and drug/inflammation interaction.
Another issue related to idiosyncratic reactions is that the ability of drugs to cause them is not identified until the drug is on the market and being used by a large population of people. A method that could predict which drugs carry this liability early in the drug development process would be beneficial. Using what we have learned from animal models of drug/inflammation interaction we have developed an in vitro assay that, in preliminary studies, correctly identifies drugs known to cause idiosyncratic liver injury in people. We are pursuing this avenue of investigation.
An additional area of research relates to the drug acetaminophen. This drug is responsible for many cases of drug-induced liver failure in the US. We have observed that the coagulation system is involved in liver injury in experimental animals treated with acetaminophen. The mechanisms by which the coagulation system contributes to liver damage are complex, and we are engaged in trying to understand these mechanisms.
- Prediction of idiosyncratic drug-induced liver injury from drug-cytokine interaction in vitro
- Environmental metals, excitotoxicity and ALS
- Inflammation and Drug Idiosyncrasy Dichotomous Roles of Thrombin in Acetaminophen Hepatotoxicity
Selected Honors/Awards and Achievements
- 2014 Colgate-Palmolive Grant for Alternative Research from the Society of Toxicology
- 2010 Kenneth E. Moore Distinguished Alumna Award, Department of Pharmacology and Toxicology, Michigan State University
American Society of Pharmacology and Experimental Therapeutics (ASPET)
- Chair, Division of Toxicology, 2011-2012
- Chair-Elect, Division of Toxicology, 2010-2011
- Member, Nominating Committee, 2003-2004
- Secretary-Treasurer, Division of Toxicology, 2002-2004
Society of Toxicology (SOT)
- Vice President-Elect, 2015-2016
- Board of Publications, 2013-2015
- Secretary/Treasurer, Mechanisms Specialty Section, 2010-2012
- Councilor, 2008-2010
- Member, Awards Committee, 2006-2008
- Chair, Member Services Strategy Committee, 2006-2007
- Membership Committee, 2001-2004; Chair, 2003-2004
- Councilor, Mechanisms Specialty Section, 1999-2001
- Member, Continuing Education Committee, 1998-2001
- Toxicology, 2004-present
- Journal of Pharmacology and Experimental Therapeutics, 1999-present
- Journal of Toxicology and Environmental Health, 1998-present
- Toxicological Sciences, 1999-2005
- Fundamental and Applied Toxicology, 1994-1999
Full list of publications at MSU Scholars
- Maiuri AR, Breier AB, Gora LF, Parkins RV, Ganey PE, Roth RA. Cytotoxic synergy between cytokines and NSAIDs associated with idiosyncratic hepatotoxicity is driven by mitogen-activated protein kinases. Toxic Sci 2015, 146(2): 265-280. PMID: 25953702.
- Miyakawa K, Joshi N, Sullivan BP, Albee R, Brandenberger C, Jaeschke H, McGill MR, Scott MA, Ganey PE, Luyendyk JP, Roth RA. Platelets and protease-activated receptor-4 contribute to acetaminophen-induced liver injury in mice. Blood 2015, Oct 8;126(15):1835-43. doi: 10.1182/blood-2014-09-598656. Epub 2015 Jul 15. PMID: 26179083
- Miyakawa K, Albee R, Letzig LG, Lehner AF, Scott M, Buchweitz JP, James LP, Ganey PE, Roth RA. A cytochrome P450-independent mechanism of acetaminophen-induced hepatocellular injury in cultured mouse hepatocytes. J Pharmacol Exp Ther 2015, 354(2):230-237. PMID: 26065700. Highlighted paper.
- Beggs LM, Maiuri AR, Fullerton AM, Poulsen KL, Breier AB, Ganey PE, Roth RA. Trovafloxacin-induced replication stress sensitizes HepG2 cells to tumor necrosis factor-alpha-induced cytotoxicity mediated by extracellular signal-regulated kinase and ataxia telangiectasia and Rad3-related. Toxicology 331: 35-46, 2015, PMID:25748550.
- Poulsen KL, Olivero-Verbel J, Beggs KM, Ganey PE, Roth RA. Trovafloxacin enhances LPS-stimulated production of TNF by macrophages: role of the DNA damage response. J Pharmacol Exp Ther 350(1): 164-170, 2014, PMID 24817034
- Poulsen KL, Albee RP, Ganey PE, Roth RA. Trovafloxacin potentiation of lipopolysaccharide-induced tumor necrosis factor release from RAW 264.7 cells requires ERK and JNK. J Pharmacol Exp Ther 349(2): 185-191, 2014, PMID 24525298
- Beggs KM, Fullerton AM, Miyakawa K, Ganey PE, Roth RA. Molecular Mechanisms of Hepatocellular Apoptosis Induced by Trovafloxacin-Tumor Necrosis Factor-alpha Interaction. Toxicol Sci. 2014 Jan;137(1):91-101. doi: 10.1093/toxsci/kft226. Epub 2013 Oct 4. PubMed PMID: 24097668; PubMed Central PMCID: PMC3871929.
- Fullerton AM, Roth RA, Ganey PE. Pretreatment with TCDD exacerbates liver injury from Concanavalin A: critical role for NK cells. Toxicol Sci. 2013. Nov;136(1):72-85. doi: 10.1093/toxsci/kft174. Epub 2013 Aug 22. PubMed PMID: 23970800; PubMed Central PMCID: PMC3829569.
- Lu J, Roth RA, Malle E, Ganey PE. Roles of the hemostatic system and neutrophils in liver injury from co-exposure to amiodarone and lipopolysaccharide. Toxicol Sci. 2013 Nov;136(1):51-62. doi: 10.1093/toxsci/kft170. Epub 2013 Aug 2. PubMed PMID: 23912913; PubMed Central PMCID: PMC3829566.
- Fullerton AM, Roth RA, Ganey PE. 2,3,7,8-TCDD enhances the sensitivity of mice to concanavalin A immune-mediated liver injury. Toxicol Appl Pharmacol. 2013 Jan 15;266(2):317-27. doi: 10.1016/j.taap.2012.11.009. Epub 2012 Nov 16. PubMed PMID: 23164664; PubMed Central PMCID: PMC3535831.
- Lu J, Miyakawa K, Roth RA, Ganey PE. Tumor necrosis factor-alpha potentiates the cytotoxicity of amiodarone in Hepa1c1c7 cells: roles of caspase activation and oxidative stress. Toxicol Sci. 2013 Jan;131(1):164-78. doi: 10.1093/toxsci/kfs289. Epub 2012 Oct 5. PubMed PMID: 23042730; PubMed Central PMCID: PMC3537133.