ENVIRONMENTAL HEALTH SCIENCES RESEARCH CENTER

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Frederick E. Domann, Ph.D.

Associate Professor of Radiation Oncology

Email: frederick-domann@uiowa.edu
Phone: (319) 335-8018
EHSRC Role(s): Member, Oxidative Stress and Metabolism Research Cluster

Research Interests

Dr. Domann's laboratory focuses on the transcriptional regulation of cancer related genes including oncogenes and tumor suppressor genes. Specifically, they are studying the molecular mechanisms by which aberrant cytosine methylation of CpG dinucleotides affects gene expression during the development of cancer. The lab's primary focus has been placed on the tumor suppressor gene SOD2 that encodes the antioxidant enzyme superoxide dismutase. Their studies have determined that site specific DNA methylation of the SOD2 gene promoter can suppress its transcriptional activation. Thus, cytosine methylation of genetic regulatory elements within this important tumor suppressor gene can mediate its inactivation.

The lab is also studying transcription factor AP-2 and its interactions with the SOD2 promoter. Interestingly, these interactions are affected by DNA methylation. In addition, they are also assessing chromatin accessibility in the region of the SOD2 promoter in cells that differentially express the gene. Future research directions will be aimed at elucidating the role of cytosine methylation as a mechanism for inactivation of other genes involved in protection against oxidative damage as well as other classical tumor suppressor genes, and to elucidate the mechanism(s) by which CpG methylation can bring about these changes in gene expression.

The Domann lab has recently become interested in cancer therapy using the human sodium iodide symporter. When expression of this gene is activated, either by gene transfer of epigenetic reactivation, tumor cells acquire the thyroid-like phenotype of iodide concentration. This activity can be exploited as a tool for imaging gene delivery and expression in humans in clinical translational trials of gene therapy; or as a means to deliver therapy itself depnding on which radioisotope of iodine is used.

Recent Publications

  1. Menon SG, Sarsour EH, Kalen AL, Venkataraman S, Hitchler MJ, Domann FE, Oberley LW, Goswami PC. Superoxide signaling mediates N-acetyl-L-cysteine-induced G1 arrest: regulatory role of cyclin D1 and manganese superoxide dismutase. Cancer Res. 2007 Jul 1;67(13):6392-9.
  2. Bock JM, Menon SG, Sinclair LL, Bedford NS, Goswami PC, Domann FE, Trask DK. Celecoxib toxicity is cell cycle phase specific. Cancer Res. 2007 Apr 15;67(8):3801-8. PMID: 17440094
  3. Bock JM, Menon SG, Goswami PC, Sinclair LL, Bedford NS, Domann FE, Trask DK. Relative non-steroidal anti-inflammatory drug (NSAID) antiproliferative activity is mediated through p21-induced G1 arrest and E2F inhibition. Mol Carcinog. 2007 Apr 5; [Epub ahead of print]
  4. Tompkins VS, Hagen J, Frazier AA, Lushnikova T, Fitzgerald MP, di Tommaso A, Ladeveze V, Domann FE, Eischen CM, Quelle DE. A novel nuclear interactor of ARF and MDM2 (NIAM) that maintains chromosomal stability. J Biol Chem. 2007 Jan 12;282(2):1322-33. Epub 2006 Nov 16. PMID: 17110379
  5. Yu L, Venkataraman S, Coleman MC, Spitz DR, Wertz PW, Domann FE. Glutathione peroxidase-1 inhibits UVA-induced AP-2alpha expression in human keratinocytes. Biochem Biophys Res Commun. 2006 Dec 29;351(4):1066-71. Epub 2006 Nov 7.
  6. Lal G, Padmanabha L, Smith BJ, Nicholson RM, Howe JR, O'Dorisio MS, Domann FE Jr. RIZ1 is epigenetically inactivated by promoter hypermethylation in thyroid carcinoma. Cancer. 2006 Dec 15;107(12):2752-9.
  7. Berger KL, Barriga F, Lace MJ, Turek LP, Zamba GJ, Domann FE, Lee JH, Klingelhutz AJ. Cervical keratinocytes containing stably replicating extrachromosomal HPV-16 are refractory to transformation by oncogenic H-Ras. Virology. 2006 Dec 5-20;356(1-2):68-78. Epub 2006 Aug 30. PMID: 16945398
  8. Zhao R, Domann FE, Zhong W. Apoptosis induced by selenomethionine and methioninase is superoxide mediated and p53 dependent in human prostate cancer cells. Mol Cancer Ther. 2006 Dec;5(12):3275-84. PMID: 17172431
  9. Darbro BW, Lee KM, Nguyen NK, Domann FE, Klingelhutz AJ. Methylation of the p16(INK4a) promoter region in telomerase immortalized human keratinocytes co-cultured with feeder cells. Oncogene. 2006 Nov 30;25(56):7421-33. Epub 2006 Jun 12.
  10. Yu L, Domann FE. Rapid and direct quantitative RT-PCR method to measure promoter activity. Biotechnol Prog. 2006 Sep-Oct;22(5):1461-3.
  11. Li H, Watts GS, Oshiro MM, Futscher BW, Domann FE. AP-2alpha and AP-2gamma are transcriptional targets of p53 in human breast carcinoma cells. Oncogene. 2006 Aug 31;25(39):5405-15. Epub 2006 Apr 24.
  12. Slane BG, Aykin-Burns N, Smith BJ, Kalen AL, Goswami PC, Domann FE, Spitz DR. Mutation of succinate dehydrogenase subunit C results in increased O2.-, oxidative stress, and genomic instability. Cancer Res. 2006 Aug 1;66(15):7615-20.
  13. Rose SL, Fitzgerald MP, White NO, Hitchler MJ, Futscher BW, De Geest K, Domann FE. Epigenetic regulation of maspin expression in human ovarian carcinoma cells. Gynecol Oncol. 2006 Aug;102(2):319-24. Epub 2006 Feb 7.
  14. Moussavi-Harami F, Mollano A, Martin JA, Ayoob A, Domann FE, Gitelis S, Buckwalter JA. Intrinsic radiation resistance in human chondrosarcoma cells. Biochem Biophys Res Commun. 2006 Jul 28;346(2):379-85. Epub 2006 Jun 5.
  15. Luo J, Li L, Zhang Y, Spitz DR, Buettner GR, Oberley LW, Domann FE. Inactivation of primary antioxidant enzymes in mouse keratinocytes by photodynamically generated singlet oxygen. Antioxid Redox Signal. 2006 Jul-Aug;8(7-8):1307-14.
  16. Li H, Goswami PC, Domann FE. AP-2gamma induces p21 expression, arrests cell cycle, and inhibits the tumor growth of human carcinoma cells. Neoplasia. 2006 Jul;8(7):568-77.
  17. Niu G, Anderson RD, Madsen MT, Graham MM, Oberley LW, Domann FE. Dual-expressing adenoviral vectors encoding the sodium iodide symporter for use in noninvasive radiological imaging of therapeutic gene transfer. Nucl Med Biol. 2006 Apr;33(3):391-8.
  18. Zhao R, Xiang N, Domann FE, Zhong W. Expression of p53 enhances selenite-induced superoxide production and apoptosis in human prostate cancer cells. Cancer Res. 2006 Feb 15;66(4):2296-304.
  19. Andringa KK, Coleman MC, Aykin-Burns N, Hitchler MJ, Walsh SA, Domann FE, Spitz DR. Inhibition of glutamate cysteine ligase activity sensitizes human breast cancer cells to the toxicity of 2-deoxy-D-glucose. Cancer Res. 2006 Feb 1;66(3):1605-10.

  Environmental Health Sciences Research Center, The University of Iowa, 100 Oakdale Campus, #178 IREH, Iowa City, IA 52242

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