- My laboratory focuses on the transcriptional regulation of cancer related genes including oncogenes and tumor suppressor genes. Specifically, we are studying the molecular mechanisms by which aberrant cytosine methylation of CpG dinucleotides affects gene expression during the development of cancer. We have focused primarily on the tumor suppressor gene SOD2 that encodes the antioxidant enzyme superoxide dismutase. We 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.
- We are also studying transcription factor AP-2 and its interactions with the SOD2 promoter. Interestingly, these interactions are affected by DNA methylation. We are also assessing chromatin accessibility in the region of the SOD2 promoter in cells that differentially express the gene. Our 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.
- We have recently been studying mechanisms underlying the transcriptional silencing of another tumor suppressor gene of particular interest to breast cancer etiology. We have determined that the maspin gene is transcriptionally silenced in the majority of advanced human breast cancers by an epigenetic mechanism involving aberrant cytosine methylation and chromatin condensation of the maspin gene promoter. We are continuing to investigate the mechanisms that contribute to transcriptional regulation of the maspin gene in human cancer.
- Cyr AR, Kulak MV, Park JM, Bogachek MV, Spanheimer PM, Woodfield GW,
White-Baer LS, O'Malley YQ, Sugg SL, Olivier AK, Zhang W, Domann FE, Weigel RJ.
TFAP2C governs the luminal epithelial phenotype in mammary development and
carcinogenesis. Oncogene. 2014 Jan 27. doi: 10.1038/onc.2013.569. [Epub ahead of
print] PubMed PMID: 24469049.
- Case AJ, Domann FE. Absence of manganese superoxide dismutase delays
p53-induced tumor formation. Redox Biol. 2014 Jan 13;2:220-3. doi:
10.1016/j.redox.2014.01.001. eCollection 2014. PubMed PMID: 24494196; PubMed
Central PMCID: PMC3909777.
- Place TL, Nauseef JT, Peterson MK, Henry MD, Mezhir JJ, Domann FE.
Prolyl-4-hydroxylase 3 (PHD3) expression is downregulated during
epithelial-to-mesenchymal transition. PLoS One. 2013 Dec 18;8(12):e83021. doi:
10.1371/journal.pone.0083021. eCollection 2013. PubMed PMID: 24367580; PubMed
Central PMCID: PMC3867438.
- Vorrink SU, Severson PL, Kulak MV, Futscher BW, Domann FE. Hypoxia perturbs
aryl hydrocarbon receptor signaling and CYP1A1 expression induced by PCB 126 in
human skin and liver-derived cell lines. Toxicol Appl Pharmacol. 2014 Feb
1;274(3):408-16. doi: 10.1016/j.taap.2013.12.002. Epub 2013 Dec 16. PubMed PMID:
24355420; PubMed Central PMCID: PMC3919493.
- Teoh-Fitzgerald ML, Fitzgerald MP, Zhong W, Askeland RW, Domann FE. Epigenetic
reprogramming governs EcSOD expression during human mammary epithelial cell
differentiation, tumorigenesis and metastasis. Oncogene. 2014 Jan
16;33(3):358-68. doi: 10.1038/onc.2012.582. Epub 2013 Jan 14. PubMed PMID:
23318435; PubMed Central PMCID: PMC3711965.
- Case AJ, Madsen JM, Motto DG, Meyerholz DK, Domann FE. Manganese superoxide
dismutase depletion in murine hematopoietic stem cells perturbs iron homeostasis,
globin switching, and epigenetic control in erythrocyte precursor cells. Free
Radic Biol Med. 2013 Mar;56:17-27. doi: 10.1016/j.freeradbiomed.2012.11.018. Epub
2012 Dec 5. PubMed PMID: 23219873; PubMed Central PMCID: PMC3578015.
Complete Publications| Google Scholar | Pubmed
Honors, Awards and Organizations
- 2011 Radiation Research Society -Distinguished Alumnus of the University of Wisconsin Platteville.
- 1997 Radiation Research Society Travel Award (Yuanhui Huang).
- 1996 Presidential Young Investigator Award, The Oxygen Society (Yuanhui Huang).
- 1996 Radiological Society of North America/Fuji Film Seed Grant Award.
- 1995 Outstanding Recent Alumnus Award, University of Wisconsin- Platteville.
- 1994 Cancer Research Award, Ladies Auxilliary VFW, Iowa Chapter.
- 1993-94 Central Investment Fund for Research Enhancement, Vice President for Research, The University of Iowa.
- 1992-93 NIH/NRSA Postdoctoral Training Grant Recipient, Pharmacology and Toxicology, University of Arizona.
- 1991 International Congress of Radiation Research Student Travel Award.
- 1989-91 NIH/NRSA Predoctoral Training Grant Recipient, Human Cancer Biology, University of Wisconsin.
- 1989-90 Radiation Research Society Student Travel Award.
- 1984 Human Oncology Special Fellowship, University of Wisconsin- Madison.
- 1982 Leo E. Boebel Memorial Biology Scholarship, University of Wisconsin-Platteville.
PhD Human Cancer Biology, University of Wisconsin-Madison 1991
BS Chemistry, University of Wisconsin-Platteville, 1983 (Magna cum laude)
The University of Arizona, Department of Radiation Oncology, Arizona Cancer Center, Postdoctoral Research Associate, 1991-1992.
The University of Arizona, Department of Pharmacology & Toxicology,Arizona Cancer Center, NIH/NRSA Postdoctoral Trainee, 1992-1993