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Christopher A. Reilly

Research Assistant Professor of Pharmacology and Toxicology

Education and Training

BS, 1994, University of Utah. Bioloigy, minor in Chemistry

PhD, 1999, Utah State University, Toxicology

Research Interests

Overview:
Our laboratory has three principal areas of focus:  TRP ion channels in lung physiology and disease, Mechanistic studies of drug metabolizing enzymes, and Biological applications of mass spectrometry.

TRP ion channels are a family of ion channels that exhibit unique functional properties and associated physiological functions ranging from sensory perception to regulation of cellular homeostasis.  We are interested in how TRP channels regulate physiological and adverse events in the lung, with particular emphasis on the ability of these channels to elicit deleterious pulmonary inflammation and lung cell death when exposed to endogenous and exogenous agonists; pulmonary inflammation and acute lung damage are two critical components of lung diseases such as asthma, fibrosis, and sepsis.  We primarily study TRPV1 and TRPM8 which sense the irritants capsaicin and menthol.  We are interested in establishing roles for these channels in the development and progression of lung diseases and have an active research program investigating cellular pathways and endogenous substances that modulate lung function and homeostasis during inflammatory insults and experimentally-induced disease states.

Xenobiotic metabolism is collective process by which chemicals are created and/or destroyed in our bodies.  Our group is interested in how human P450 enzymes transform chemicals to inactive and toxic reactive electrophiles that damage cellular macromolecules.  We have two primary areas of focus; enzymatic/chemical mechanisms of oxygenation vs. dehydrogenation of substrates and analysis of modified biological macromolecules (i.e., DNA and protein) by electrophiles.  Our studies aim to establish biochemical mechanisms that dictate the formation of certain types of metabolites using metabolic profiling techniques and mass spectrometry.  We are also interested in defining relationships between electrophile-induced modification of DNA and protein as a mechanism of lung cell injury by the pneumotoxicant 3-methylindole.  These studies are performed in collaboration with Dr. Garold S. Yost.

Mass spectrometry is a versatile and definitive analytical technology that has revolutionized mechanistic toxicology studies.  In addition to the use of mass spectrometry to quantify substances in diverse matrices (e.g., capsaicinoids, steroid mimics), we utilize this technique to establish structures of metabolites of P450 reactions, to discover unknown bioactive substances that have measurable biological activity (e.g., enzyme inhibition or toxicity), and to identify macromolecular targets of electrophiles generated by P450s.  A new area of research in the laboratory is the use of quantitative proteomics methods to study cellular sub-proteomes.  Through these studies we are establishing mechanisms of toxicity for known pneumotoxicants as well as identifying essential gene products that regulate toxicity in lung cells.

Selected Publications

TRP Ion Channels and Lung Physiology and Diseases:

1. Reilly, C.A., Taylor, J.L., Lanza, D.L., Carr, B.A., Crouch, D.J., and Yost, G.S.  (2003) Capsaicinoids Cause Inflammation and Epithelial Cell Death Through Activation of Vanilloid Receptors.  Toxicol. Sci. 73, 170-181.
2. Veranth, J.M., Reilly, C.A., Veranth, M.M., Moss, T.A., Langelier, C.R., Lanza, D.L., and Yost, G.S. (2004) Inflammatory cytokines and cell death in BEAS-2B lung cells treated with soil dust, Lipopolysaccharide, and surface-modified particles.  Toxicol. Sci. 82, 88-96.
3. Reilly, C.A., Johansen, M.E., Lanza, D.L., Lee, J., Lim, J-O., and Yost, G.S. (2005) Activation of TRPV1 in Bronchiolar Epithelial Cells Promotes Inflammatory Cytokine Production and Cell Death via Separate Calcium-Dependent and Independent Pathways  J Biochem. Mol. Toxicol., 19(4), 266-275.
4. Johansen M.E., Reilly C.A., and Yost G.S. (2006) TRPV1 Antagonists Elevate Cell Surface Populations of Receptor Protein and Exacerbate TRPV1-Mediated Toxicities in Human Lung Epithelial Cells.  Toxicol. Sci.,89(1), 278-286.
5. Reilly, C.A., Veranth, J.M., Veronesi, B., and Yost, G.S. (2006)  Vanilloid Receptors in Respiratory Tissues:  Identification, Function, Significance, and Potential Involvement in Human Airway Disease.  In:  Toxicology of the Lung 4th ed., pp. 297-350 (Gardner, D. Ed.) CRC-Press, Taylor and Francis, London, UK.
6. Thomas, K.C., Sabnis, A.S., Johansen, M.E., Moos, P.J., Yost, G.S., and Reilly, C.A. (2007) TRPV1 Agonists Cause Endoplasmic Reticulum Stress and Cell Death in Human Lung Cells. J. Pharmcol. Exp. Therap. 321(3), 830-838.

Xenobiotic Metabolism:

1. Reilly, C.A., Ehlhardt, W.J., Jackson, D.A.,  Kulanthaivel P., Mutlib, A.E., Espina, R.J., Moody D.E, Crouch, D.J., and Yost, G.S. (2003) Metabolism of Capsaicin by Cytochrome P450 Produces Novel Dehydrogenated Metabolites and Decreases Cytotoxicity to Lung and Liver Cells.  Chem. Res. Toxicol.  16(3), 336-349.
2. Simmonds, A.C., Reilly, C.A., Baldwin, R.M., Ghanayem, B.I., Lanza, D.L., Yost, G.S., Collins, K.S., and Forkert, P.G.  (2004)  Bioactivation of 1,1-dichloroethylene to its epoxide by CYP2E1 and CYP2F enzymes.  Drug Metab. Disp. 32(9), 1032-1039.
3. Reilly, C.A. and Yost, G.S. (2005) Structural and Enzymatic Parameters that Determine Alkyl Dehydrogenation/Hydroxylation of Capsaicinoids by P450 Enzymes. Drug Metab. Disp., 33(4), 530-6.
4. Reilly, C.A. and Yost, G.S.  (2006)  Metabolism of Capsaicinoids by P450 Enzymes:  A Review of Recent Findings on Reaction Mechanisms, Bio-Activation, and Detoxification Processes.  Drug Metabolism Reviews 38(4), 685-706.
5. Sun H., Ehlhardt, W.J., Kulanthaivel, P., Lanza, D.L., Reilly, C.A., and Yost G.S. (2007) Dehydrogenation of Indoline by Cytochrome P450 Enzymes: A Novel “Aromatase” Process. J. Pharmacol. Exp. Therap. 322(2), 843-851.

Biological Applications of Mass Spectrometry:

1. Reilly, C.A., Crouch, D.J., Fatah, A.A., and Yost, G.S. (2001)  Determination of Capsaicin, Dihydrocapsaicin, and Nonivamide in Self-Defense Weapons by Liquid Chromatography-Mass Spectrometry and Liquid Chromatography-Tandem Mass Spectrometry.  J. Chromatogr. A  912, 259-267.
2. Welch, K.D., Reilly, C.A., and Aust, S.D. (2002)  The Role of Cysteine Residues in the Oxidation of Ferritin.  Free Rad. Biol. Med.  33, 399-408.
3. Reilly, C.A., Crouch, D.J., Yost, G.S., and Fatah, A.A. (2002)  Determination of Capsaicin, Nonivamide, and Dihydrocapsaicin in Blood and Tissue by Liquid Chromatography-Tandem Mass Spectrometry.  J. Analyt. Toxicol.  26, 313-319.
4. Pershing, L.K., Reilly, C.A., and Crouch, D.J.  (2004)  Effects Of Vehicle On The Uptake And Elimination Kinetics Of  Capsaicinoids In Human Skin In Vivo.  Toxicol. Appl. Pharmacol. 200, 73-81.
5. Reilly, C.A. and Crouch, D.J. (2003) Analysis of the Nutritional Supplement 1AD, Its Metabolites, and Related Endogenous Hormones in Biological Matrices Using Liquid Chromatography-Tandem Mass Spectrometry.  J. Analyt. Toxicol. 28, 1-10.
6. Phillips, J.D., Bergonia, H., Reilly, C.A., Franklin, M.R., and Kushner, J.P.  (2006)  A Porphomethene Inhibitor of Uroporphyrinogen Decarboxylase Causes Porphyria Cutanea Tarda.  Proc. Nat. Acad. Sci., 104(12), 5079-5084.

Pharmacology & Toxicology   College of Pharmacy   30 S. 2000 E., Rm 201, SLC  UT 84112  phone: 801-581-6287  fax: 801-585-5111 phtx@pharm.utah.edu