Phillip Moos

Assistant Professor of Pharmacology and Toxicology

Philip J. Moos Title: Assistant Professor of Pharmacology and Toxicology
Email address: philip.moos@pharm.utah.edu

Education and Training:

1989 - B.S. Aerospace Engineering Sciences, University of Colorado, Boulder, CO.
1990 - M.S. Aerospace Engineering Sciences, University of Colorado, Boulder, CO.
1994 - Ph.D. Biology, Kansas State University, Manhattan, KS.

Research Interests:

The Moos laboratory is broadly interested in understanding cancer susceptibility with an emphasis toward prevention. Research efforts are focused on cancer genomics, mechanisms of disease, and modifiers of cancer risk, with a particular emphasis on the role of inflammation in cancer risk.

Current work is primarily in two arenas: 1) elucidation of the role of select selenoproteins in cellular redox control and carcinogenesis, and 2) genomic evaluation of nanoparticles for inflammatory potential or other toxic adverse effects.

The first area of research is derived from studies to understand how chronic inflammation increases the risk for cancer. The focus is on electrophilic lipids of arachidonate metabolism and their cellular targets. We found that certain lipid electrophiles inhibit the tumor suppressor, p53, through an indirect mechanism of partially inactivating the selenoprotein, thioredoxin reductase. This work provides a framework to integrate several concepts: 1) how electrophiles, particularly those from inflammation, might participate in carcinogenesis; 2) how selenoproteins and dietary selenium may confer protection against cancer; and 3) how cells might acquire an unusual and unexplained p53 phenotype observed in some tumors.

The second, and newer, area of research utilizes transcript profiling and apoptotic studies to evaluate particulate matter toxicity and inflammatory potential. We have found that certain metal oxide manufactured nanoparticles have significant toxicity and induce a cellular response to the stress of the nanoparticles. As these metals are involved in redox reactions, and selenoenzymes regulate redox reactions, we observe interactions that bridge these two areas of research.

Selected Publications:

Oxidation of 2 Cys-Peroxiredoxins by Lipid Hydroperoxide Metabolites of Lipoxygenase and Cyclooxygenase-2. P. Cordray, K. Doyle, K. Edes, P. J. Moos and F. A. Fitzpatrick. J. Biol. Chem (in press, Epub 2007).
Pre- and Post-Initiation Chemoprevention Activity of 2-Alkyl/Aryl Selenazolidine-4(R)-Carboxylic Acids against Tobacco-Derived Nitrosamine (NNK)-Induced Lung Tumors in the A/J Mouse. M.R. Franklin, P.J. Moos, W.M. El-Sayed, T. Aboul-Fadl, J.G. Lamb, and J.C. Roberts. Chem Biol Interact. 168:211-220, (2007).
TRPV1 Agonists Cause Endoplasmic Reticulum Stress and Cell Death in Human Lung Cells. K.C. Thomas, A.S. Sabnis, M.E. Johansen, D.L. Lanza, P.J. Moos, G.S. Yost, and C.A. Reilly. J Pharmacol Exp Ther. 321: 830-838, (2007).
Thioredoxin reductase is required for the inactivation of tumor suppressor p53 and for apoptosis induced by endogenous electrophiles. P.B. Cassidy, K. Edes, C.C. Nelson, K. Parsawar, F.A. Fitzpatrick, and P.J. Moos. Carcinogenesis, 27: 2538-2549, (2006).
Curcumin Impairs Tumor Suppressor p53 Function in Colon Cancer Cells. P.J. Moos, K. Edes, J.E. Mullally, F.A. Fitzpatrick. Carcinogenesis, 25:1611-1617 (2004).
Conditional Expression of 15-Lipoxygenase-1 Inhibits the Selenoenzyme Thioredoxin Reductase: Modulation of selenoproteins by lipoxygenase enzymes. M. Yu, P.J. Moos, P. Cassidy, M. Wade, and F.A. Fitzpatrick. J. Biol Chem., 279:28028-35 (2004).
Identification of Genes that are Transcriptionally Regulated by Myc in Childhood Tumors. E. Raetz, M.K.H. Kim, P. Moos, M. Carlson, C. Bruggers, D. Hooper, L. Foote, T. Liu, R. Seeger and W.L. Carroll, (2003), Cancer 98:841-853.
Electrophilic Prostaglandins and Lipid Aldehydes Repress Redox Sensitive Transcription Factors p53 and HIF by Impairing the Selenoprotein Thioredoxin Reductase, (2003) P.J. Moos, K. Edes, P. Cassidy, E. Massuda and F.A. Fitzpatrick, J Biol Chem. 278: 745â€“750.
Identification of Gene Expression Profiles that Segregate Patients with Childhood Leukemia, (2002) P.J. Moos, E.A. Raetz, M.A. Carlson, F.E. Smith, S.P. Hunger, Q. Wei, and W.L. Carroll, Clin. Cancer Res., 8:3118-30.
Cyclopentenone prostaglandins of the J series inhibit the ubiquitin isopeptidase activity of the proteasome pathway, (2001) J.E. Mullally, P.J. Moos, K. Edes, and F.A. Fitzpatrick, J Biol Chem. 276: 30366-30373.
Inactivation of wild-type p53 tumor suppressor by electrophilic prostaglandins, (2000) P.J. Moos, K. Edes, and F.A. Fitzpatrick, Proc. Natl. Acad. Sci. USA, 97:9215-9220.
P.B. Cassidy, K. Edes, C.C. Nelson, K. Parsawar, F.A. Fitzpatrick, and P.J. Moos . Thioredoxin reductase is required for the inactivation of tumor suppressor p53 and for apoptosis induced by endogenous electrophiles. Carcinogenesis, 27: 2538-2549, (2006).
K.C. Thomas, A.S. Sabnis, M.E. Johansen, D.L. Lanza, P.J. Moos , G.S. Yost, and C.A. Reilly. TRPV1 Agonists Cause Endoplasmic Reticulum Stress and Cell Death in Human Lung Cells. JPET. 321:830-838 (2007).
M.R. Franklin, P.J. Moos , W.M. El-Sayed, T. Aboul-Fadl, J.G. Lamb, and J.C. Roberts. Pre- and Post-Initiation Chemoprevention Activity of 2-Alkyl/Aryl Selenazolidine-4(R)-Carboxylic Acids against Tobacco-Derived Nitrosamine (NNK)-Induced Lung Tumors in the A/J Mouse. Chem Biol Interact. 168:211-220, (2007).
K. Doyle, P. Cordray, K. Edes, P.J. Moos and F. A. Fitzpatrick. Oxidation of 2 Cys-Peroxiredoxins by Lipid Hydroperoxide Metabolites of Lipoxygenase and Cyclooxygenase-2. J. Biol. Chem. 282:32623-32629, (2007).
R.L. Poerschke, M.R. Franklin, and P.J. Moos . Modulation of redox status in human lung cell lines by organoselenocompounds: selenazolidines, selenomethionine and methylseleninic acid. Toxicol In Vitro, 22: 1761-7, (2008).
R. L. Warters, A.T. Packard, G.F. Kramer, D.K. Gaffney, and P.J. Moos . Differential gene expression in primary human skin keratinocytes and fibroblasts in response to ionizing radiation. Rad Research, 172:82-95, (2009)
C. Rock and P.J. Moos . Selenoprotein P regulation by the glucocorticoid receptor. BioMetals (in press, 2009)
M. Honeggar, R. Beck, and P.J. Moos . Thioredoxin reductase 1 ablation sensitizes colon cancer cells to methylseleninate-mediated cytotoxicity. Toxicol Appl Pharmacol (in press, 2009)