Dr. Shelley Phelan
Research in Molecular & Cell Biology
My lab is interested in the cellular and molecular mechanisms that govern human disease. In particular, my research focuses on the protective role of antioxidant genes in a variety of age-related diseases including atherosclerosis, neurodegenerative disease, and cancer. We have focused much of our investigations on the regulation and function of the Peroxiredoxin 6 (Prdx6) gene, a member of a highly conserved family of thiol-specific antioxidants that protect cells from oxidative damage. The Prdx6 protein is capable of reducing hydrogen peroxide and lipid peroxides within the cell, thereby lowering reactive oxygen species and altering redox signaling. Prdx6 is highly expressed in many tissues, and has been shown by our lab and others to protect mice from cellular damage and death introduced by various oxidative stress-inducing agents. One aspect of my research uses a mouse liver cell line to elucidate the mechanism of regulation and protein function of Prdx6. We have determined several inducers of Prdx6 in liver, including hormones and growth factors such as dexamethasone, and KGF, and TNF-a. We are also studying the signal transduction pathways that mediate this induction, as well as the upstream sequence elements and transcription factors that regulate its expression. Finally, we are examining the differential regulation of this family of genes in various pathological conditions. Together, this data can provide clues to the way this important antioxidant is controlled, and will shed light on its role in normal physiology, as well as specific disease states.
Courses Taught:
- BI 83 - The DNA Revolution (Non-majors)
- BI 170 & 171 - General Biology I & II (Majors)
- BI 327 - Cell Biology
- BI 385 - Molecular Mechanisms of Human Disease Seminar (Capstone)
- BI 395 & 396 - Independent Research I & II
- BI 397 & 398 - Internships
Recent Publications:
Gallagher, B.M. & Phelan S.A. (2006). Investigating Mechanisims of Prdx6 Regulation in Mouse Liver Cells. Free Radical Biology & Medicine (Submitted).
Wang, Y. , Phelan, S.A., Manevich, Y., Feinstein, S.A., Fisher, A.B. (2006). Transgenic Mice Overexpressing Peroxiredoxin 6 Show Increased Resistance to Lung Injury in Hyperoxia. Am. J. Respir. Cell Mol. Biol., 34(4):481-6.
Simeone, M.* & Phelan, S.A. (2005). "Transcripts associated with Prdx6 (peroxiredoxin 6) and related genes in mouse." Mammalian Genome 16(2):103-11.
Wang, X., Phelan, S.A., Petros, C., Taylor, E., Ledinski, G., Jurgens, G., Forsman-Semb, K., Paigen, B. (2004). "Antioxidant Protein 2 Deficiency and Atherosclerosis Susceptibility in Mice: Significance of Genetic Background for Assessing Atherosclerosis." Atherosclerosis 177(1):61-70.
Phelan, S.A., Wang, X., Wallbrandt, P., Forsman-Semb., K., Paigen, B. (2003). "Overexpression of Peroxiredoxin VI Reduces H202 But Does Not Prevent Diet-Induced Atherosclerosis." Free Radical Biology & Medicine 35(9), 1110-1120.
Wang, X., Phelan, S.A., Forsman-Semb, K., Couturier, E.F., Brown, A., Lerner, C.P., Paigen, B. (2003). "Mice With Targeted Mutation of Peroxiredoxin 6 Develop Normally But Are Susceptible To Oxidative Stress." J Biol Chem 278(27), 25179-25190.
N. Sparling & Phelan, S.A. (2003). "Identification of multiple transcripts for antioxidant protein 2 (Aop2): Differential regulation by oxidative stress and growth factors" Redox Reports 8(2), 87-94.
Phelan, S. A., Beier, D. R., Higgins, D.C., and Paigen, B. (2002). Confirmation and high resolution mapping of an atherosclerosis susceptibility gene in mice on chromosome 1. Mammalian Genome 13(10), 548-553.
Phelan, S.A. (1999). "AOP2 (Antioxidant Protein 2): structure and function of a unique thiol-specific antioxidant." Antioxidants & Redox Signaling 1, 1-14.
Phelan, S.A., Johnson, K.A., Beier, D.R., and B.Paigen. (1998). "Characterization of the Murine Gene Encoding Aop2 (Antioxidant Protein 2) and Identification of Two Highly Related Genes." Genomics 54, 132-139.
Cai, J., Phelan, S.A., Hill, A.L. & M.R. Loeken. (1998). "Identification of a New Gene, DEP-1, That is Associated with Diabetic Embryopathy and is Regulated by the Transcription Factor Pax-3." Diabetes 47, 1803-1805.
Phelan, S.A. & M.R. Loeken. (1998). "Identification of a Novel Pax-3 DNA Binding Sequence Which is Regulated by Pax-3 in Cells." J. Biol. Chem. 273(30):19153-19159.
Hill, A.L., Phelan, S.A., & M.R. Loeken. (1998). "Reduced Expression of Pax-3 is Associated with Overexpression of cdc46 in the Mouse Embryo." Development, Genes and Evolution 208 (3):128-134.
Phelan, S.A., Ito, M., & M.R. Loeken. (1997). "Neural Tube Defects in Embryos of Diabetics: Role of the Pax-3 Gene and Apoptosis." Diabetes 46: 1189-1197.
Phelan, S.A., Lindberg, C., & K.M. Call. (1994). "Wilms' Tumor Gene, WT1, mRNA is Down- Regulated During Induction of Erythroid and Megakaryocytic Differentiation of K562 Cells." Cell Growth & Differentiation 5:677-686.
Webb, A.C., Bradley, M.K., Phelan, S.A., Wu, J.Q., & L. Gehrke. (1991). "Use of the Polymerase Chain Reaction for Screening and Evaluation of Recombinant Baculovirus Clones." Biotechniques 11:512-519.
* denotes student author
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