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University of Colorado Denver

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Cynthia Ju, PhD

Associate Professor of Immunology and Toxicology, Department of Pharmaceutical Sciences

Mailing address:

University of Colorado School of Pharmacy
Mail Stop C238
12850 E. Montview Blvd. V20-2121
Aurora, CO 80045

Office Location:

Pharmacy and Pharmaceutical Sciences Building (V20)
Second Floor
Room 2121

Lab Location:

Pharmacy and Pharmaceutical Sciences Building (V20)
Second Floor
Room 2450D

Contact:

Training and Education:

  • 1991 BSc Chemistry, Peking University, Beijing, China
  • 1995 MSc Bio-organic Chemistry, University of Victoria, British Columbia, Canada
  • 1999 PhD Drug Metabolism & Toxicology, University of Toronto, Ontario, Canada

Research Interests:

My laboratory studies the role of the innate immune system in inflammatory liver diseases caused by drugs and other hepatotoxic agents.  Drug-induced liver injury (DILI) accounts for more than 25% of liver failure cases in the ICU, and these adverse drug reactions are currently the most common cause of withdrawal of drugs from the pharmaceutical market.  The key to predicting and preventing DILI is a thorough understanding of the underlying mechanisms.

Our current research focuses on:

  1. establishing a mouse model of halothane-induced liver damage,
  2. investigating the role of hepatic macrophages, neutrophils, NK, and NKT cells in halothane-, acetaminophen-, and Con A-induced liver injury, and
  3. developing a screen assay to evaluate drug candidates’ potential of causing immune reactions. 

Findings from these studies are expected to contribute to the ultimate goals of identifying mechanistic features and predisposing factors that determine patients’ susceptibility to DILI and developing diagnostic tests to predict a candidate drug’s potential of causing DILI. 

Teaching:

Professional Program Courses:
  • 2003 – present PHRD 4750, Integrated Organ System VI
  • 2003 – present PHRD 4200, Instructional Methods II
Graduate Program Courses:
  • 2003 – present TXCL 7322, Reactive Metabolites and Immunology
  • 2004 – present TXCL 7325, Current Topics in Toxicology Research
  • 2007 – present PHSC & TXCL 7310, Fundamentals of Pharmaceutical Sciences

PUBLICATIONS

Refereed Journals Published Papers

  • L. Cheng, Q. You, H. Yin, M.P. Holt, and C. Ju (2010) “Involvement of Natural Killer T Cells in Halothane-Induced Liver Injury in Mice”, Biochem. Pharmacol., 80: 255-261.
  • B.V. Martin-Murphy, M.P. Holt, and C.Ju (2010) “Role of Damage-Associated Molecular Pattern Molecules in Acetaminophen-Induced Liver Injury”, Toxicol. Lett., 192: 387-394
  • M.P. Holt, H. Yin, L. Cheng, and C. Ju (2010) “Exacerbation of Acetaminophen-Induced Disturbances of Liver Sinusoidal Endothelial Cells in the Absence of Kupffer Cells in Mice”, Toxicol. Lett., 194: 34-41.
  • Q. You, L. Cheng, and C. Ju (2010) “Generation of T Cell Responses Targeting the Reactive Metabolite of Halothane”, Toxicol. Lett., 194: 79-85.
  • H. Yin, L. Cheng, C Agarwal, R. Agarwal, and C. Ju (2010) “Lactoferrin Protects Against Concanavalin A-Induced Liver Injury in Mice”, Liver Int., 30: 623-632.
  • H. Yin, L. Cheng, M.P. Holt, N. Hail, R. MacLaren, and C. Ju (2010) “Lactoferrin Protects Against Acetaminophen-Induced Liver Injury in Mice”, Hepatology, 51: 1007-1016.
  • L. Cheng, Q. You, H. Yin, M.P. Holt, C. Franklin, and C. Ju (2009) “The Effect of PolyI:C Co-treatment on Halothane-Induced Liver Injury in Mice”, Hepatology, 49, 215-226.
  • M.P. Holt, L. Cheng, and C. Ju(2008) “Identification and Characterization of Infiltrating Macrophages in Acetaminophen-Induced Liver Injury”, J. Leukoc. Biol., 84, 1410-1421.
  • Q. You, L. Cheng, R.M. Kedl, and C. Ju (2008) “Mechanism of T cell Tolerance Induction by Hepatic Kupffer Cells”, Hepatology, 48, 978-990.
  • L. Cheng, B.J. Stewart, Q. You, D.R. Petersen, J.A. Ware, J.R. Piccotti, T.T. Kawabata, C. Ju (2008) “Covalent Binding of the Nitroso Metabolite of Sulfamethoxazole Is Important in Induction of Drug-Specific T Cell Responses In Vivo”, Molecular Pharmacology, 73: 1769-1775.
  • H. yIN, L. Cheng, R. Langenbach, and C. Ju (2007) “Prostaglandin I2 and E2 Mediate the Protective Effects of Cyclooxygenase-2 in a Mouse Model of Immune-Mediated Liver Injury”, Hepatology, 45: 159-169.
  • Q. You, L. Cheng, T. P. Reilly, D. Wegmann and C. Ju (2006) “Role of Neutrophils in a Mouse Model of Halothane-Induced Liver Injury”, Hepatology, 44: 1421-1431.
  • C. Ju, J.P. McCoy, C.J. Chung, M.L.M. Graf, and L. R. Pohl (2003) “Tolerogenic role of Kupffer cells in allergic reactions”, Chem. Res. Toxicol. 16: 1514-1519.
  • C. Ju, T. P. Reilly, M. Bourdi, M. F. Radonovich, J.N. Brady, J. W. George and L. R. Pohl (2002) “Protective role of Kupffer cells in acetaminophen-induced hepatic injury in mice”, Chem. Res. Toxicol. 15: 1504-1513.
  • C. Ju and L. R. Pohl (2001) “Immunohistochemical detection of protein adducts of 2,4-dinitrochlorobenzene in antigen presenting cells and lymphocytes after oral administration to mice: lack of a role of Kupffer cells in oral tolerance”, Chem. Res. Toxicol. 14: 1209-1217.
  • C. Ju and J. P. Uetrecht (1999) "Oxidation of 2-hydroxyiminostilbene, a metabolite of carbamazepine, to a reactive iminoquinone intermediate and detection of the glucuronide conjugate of 2-hydroxyiminostilbene in patient urine", J. Pharm. Exp. Ther. 288: 51-56.
  • C. Ju and J. P. Uetrecht (1998) "Oxidation of a metabolite of indomethacin (DMBI) to reactive intermediates by activated neutrophils, HOCl and the myeloperoxidase system”, Drug Metab.Dispos. 26: 676-680.
  • C. Ju and C. Bohne (1996) "Dynamics of probe complexation to bile salt aggregates", J. Phys. Chem. 100: 3847-3854.
  • C. Ju and C. Bohne (1996) "Probing bile salt aggregates by fluorescence quenching", Photochem. Photobiol. 63: 60-67.

Review Articles

  • C. Ju (2009) “The Role of Hepatic Macrophages in Regulation of Idiosyncratic Drug Reactions”, Toxicologic Pathology, 37, 12-7.
  • M.P. Holt and C. Ju (2006) “Mechanisms of Drug-Induced Liver Injury”, AAPS Journal, 8(1), E48-54.
  • R.A. Roberts, P.E. Ganey, C. Ju, L.M. Kamendulis, I. Rusyn, and J.E. Klaunig (2006) “Role of the Kupffer Cells in Mediating Hepatic Toxicity and Carcinogenesis”, Toxicological Sciences.
  • C. Ju and Lance R. Pohl (2005) “Tolerogenic role of Kupffer cells in immune-mediated adverse drug reactions”, Toxicology, 209: 109-112.
  • C. Ju (2005) “Immunological mechanisms of drug-induced liver injury”, Current Opinion in Drug Discovery and Development, 8: 38-43.
  • T. P. Reilly and C. Ju (2002) “Mechanisms responsible for sulfonamide-induced cutaneous reactions”, Curr. Opin. Allergy Clin. Immunol. 2: 307-315.
  • C. Ju and J. P. Uetrecht (2001) “Mechanism of idiosyncratic drug reactions: reactive metabolite formation, protein binding and the regulation of the immune system”, Curr. Drug Metab. 3: 367-377.

Book Chapters

  • M.P. Holt, and C. Ju (2008) “Organ Specific Toxicity”.  In: Molecular Toxicology – Prediction of Toxicity Parameters.  Editors: B.K. Park, D. Williams, and D. Antoine.  Publisher: Wiley-VCH.
  • M.P. Holt, and C. Ju (2008) “The Adaptive Immune System and Liver Toxicity”.  In: Comprehensive Toxicology, 2nd edition.  Editor: C.A. McQueen.  Publisher: Elsevier. 
  • M.P. Holt, and C. Ju (2010) “Drug-Induced Liver Injury”.  Handb Exp Pharmacol, 196: 3-27.