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.
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 three arenas: 1) elucidation of the role of select selenoproteins in cellular redox control and carcinogenesis, 2) combining genomics and drug screens to identify novel therapeutic agents, and 3) genomic evaluation of nanoparticles for inflammatory potential or other toxic adverse effects.
The first area of research focuses on the selenoenzyme thioredoxin reductase. This enzyme has multiple roles in cellular redox regulation and viability, making it a potential target in cancer therapeutic strategies. However, our work and others have demonstrated that, as a sole target, inhibition rarely results in loss of viability. Instead, inhibition of thioredoxin reductase potentiates other therapeutics and therefore may be a useful target for new combination therapies for some cancer phenotypes.
The second area has been initiated in collaboration Dr. Bild. We have focused our efforts on identifying new agents for cancers without targeted therapies. To date, we have utilized a broad range of lung and breast cancer cells with known genetic and genomic character to screen unique chemical libraries for new potential therapeutics.
The third 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. Nanomaterials provide many benefits and are being utilized more broadly so it is important to understand the potential toxicities, and mitigation strategies prior to use. Therefore, we collaborate with Dr. Ghandehari’s group to understand the basis of the toxicology of materials with the potential for biomedical application.
1. Genomic classification of the RAS network identifies a personalized treatment strategy for lung cancer. El-Chaar NN, Piccolo SR, Boucher KM, Cohen AL, Chang JT, Moos PJ, Bild AH. Mol Oncol. 2014 Oct;8(7):1339-54. doi: 10.1016/j.molonc.2014.05.005.
2. A chimeric p53 evades mutant p53 transdominant inhibition in cancer cells. Okal A, Mossalam M, Matissek KJ, Dixon AS, Moos PJ, Lim CS. Mol Pharm. 2013 Oct 7;10(10):3922-33. doi: 10.1021/mp400379c.
3. Transcriptional responses of human aortic endothelial cells to nanoconstructs used in biomedical applications. Moos PJ, Honeggar M, Malugin A, Herd H, Thiagarajan G, Ghandehari H. Mol Pharm. 2013 Aug 5;10(8):3242-52. doi: 10.1021/mp400285u.
4. Selenium for the prevention of cutaneous melanoma. Cassidy PB, Fain HD, Cassidy JP Jr, Tran SM, Moos PJ, Boucher KM, Gerads R, Florell SR, Grossman D, Leachman SA. Nutrients. 2013 Mar 7;5(3):725-49. doi: 10.3390/nu5030725.
5. Major differences among chemopreventive organoselenocompounds in the sustained elevation of cytoprotective genes. Poerschke RL, Franklin MR, Bild AH, Moos PJ. J Biochem Mol Toxicol. 2012 Sep;26(9):344-53. doi: 10.1002/jbt.21427.
6. A genomic approach to predict synergistic combinations for breast cancer treatment. Soldi R, Cohen AL, Cheng L, Sun Y, Moos PJ, Bild AH. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48.
7. Responses of human cells to ZnO nanoparticles: a gene transcription study. Moos PJ, Olszewski K, Honeggar M, Cassidy P, Leachman S, Woessner D, Cutler NS, Veranth JM. Metallomics. 2011 Nov;3(11):1199-211. doi: 10.1039/c1mt00061f.
8. Thioredoxin reductase 1 knockdown enhances selenazolidine cytotoxicity in human lung cancer cells via mitochondrial dysfunction. Poerschke RL, Moos PJ. Biochem Pharmacol. 2011 Jan 15;81(2):211-21. doi: 10.1016/j.bcp.2010.09.024.
9. Selenoprotein P protects cells from lipid hydroperoxides generated by 15-LOX-1. Rock C, Moos PJ. Prostaglandins Leukot Essent Fatty Acids. 2010 Oct-Dec;83(4-6):203-10. doi: 10.1016/j.plefa.2010.08.006.
10. ZnO particulate matter requires cell contact for toxicity in human colon cancer cells. Moos PJ, Chung K, Woessner D, Honeggar M, Cutler NS, Veranth JM. Chem Res Toxicol. 2010 Apr 19;23(4):733-9. doi: 10.1021/tx900203v.
11. JS-K, a nitric oxide prodrug, has enhanced cytotoxicity in colon cancer cells with knockdown of thioredoxin reductase 1. Edes K, Cassidy P, Shami PJ, Moos PJ. PLoS One. 2010 Jan 20;5(1):e8786. doi: 10.1371/journal.pone.0008786.
12. Thioredoxin reductase 1 ablation sensitizes colon cancer cells to methylseleninate-mediated cytotoxicity. Honeggar M, Beck R, Moos PJ. Toxicol Appl Pharmacol. 2009 Dec 15;241(3):348-55. doi: 10.1016/j.taap.2009.09.010.
13. Differential gene expression in primary human skin keratinocytes and fibroblasts in response to ionizing radiation. Warters RL, Packard AT, Kramer GF, Gaffney DK, Moos PJ. Radiat Res. 2009 Jul;172(1):82-95. doi: 10.1667/RR1677.1.
14. Selenoprotein P regulation by the glucocorticoid receptor. Rock C, Moos PJ. Biometals. 2009 Dec;22(6):995-1009. doi: 10.1007/s10534-009-9251-2.
15. Modulation of redox status in human lung cell lines by organoselenocompounds: selenazolidines, selenomethionine, and methylseleninic acid. Poerschke RL, Franklin MR, Moos PJ. Toxicol In Vitro. 2008 Oct;22(7):1761-7. doi: 10.1016/j.tiv.2008.08.003.
16. Oxidation of 2-Cys-peroxiredoxins by arachidonic acid peroxide metabolites of lipoxygenases and cyclooxygenase-2. Cordray P, Doyle K, Edes K, Moos PJ, Fitzpatrick FA. J Biol Chem. 2007 Nov 9;282(45):32623-9
17. 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. Franklin MR, Moos PJ, El-Sayed WM, Aboul-Fadl T, Roberts JC. Chem Biol Interact. 2007 Jul 20;168(3):211-20.
18. Transient receptor potential vanilloid 1 agonists cause endoplasmic reticulum stress and cell death in human lung cells. Thomas KC, Sabnis AS, Johansen ME, Lanza DL, Moos PJ, Yost GS, Reilly CA. J Pharmacol Exp Ther. 2007 Jun;321(3):830-8.
19. Thioredoxin reductase is required for the inactivation of tumor suppressor p53 and for apoptosis induced by endogenous electrophiles. Cassidy PB, Edes K, Nelson CC, Parsawar K, Fitzpatrick FA, Moos PJ. Carcinogenesis. 2006 Dec;27(12):2538-49.