Karen Cowden Dahl, Ph.D.
Associate Professor of Biochemistry and Molecular Biology
Indiana University School of Medicine-South Bend
Associate Adjunct Professor, Chemistry and Biochemistry
University of Notre Dame
Ph. D. University of Pennsylvania
Postdoctoral fellowship, University of New Mexico
Research Assistant Professor, University of New Mexico
Ovarian cancer is the 5th leading cause of cancer death in women in the US. The vast majority of women (>70% in the US) diagnosed with ovarian cancer have advanced disease at the time of diagnosis (the tumor has spread or metastasized). For these women the survival rates are less that 25%. Importantly ovarian cancer is >90% curable if detected early (prior to metastatic spread). Unfortunately at this point in time we do not have a good understanding of ovarian cancer at the molecular level. The goal of my laboratory is to study the molecules that are important in promoting ovarian cancer progression. In particular I want to determine how a tumor “learns” how to metastasize so that we can better prevent, diagnose, and treat ovarian cancer.
One of the molecules involved in ovarian cancer progression is the epithelial growth factor receptor (EGFR). EGFR is overexpressed in at least 70% of ovarian cancer. Its expression correlates with poor survival rates. Over the past few years I have focused on the genes that are controlled by EGFR that regulate cancer progression. We are investigating how the ARID3B transcription factor is regulated by EGFR signaling and its involvement in cancer. ARID3B is a member of the ARID family of DNA binding proteins. We have found that ARID3B is overexpressed in ovarian cancer. By understanding the gene networks that are dysfunctional in ovarian cancer we will be better equipped to diagnose and treat this disease.
The first goal of my laboratory is to elucidate the functions of ARID3B. We have three main goals: 1) how is ARID3B regulated, 2) what are the targets and functions of ARID3B, and 3) how do these proteins contribute to normal cellular differentiation and cancer progression. Our data suggest that ARID3B is critical to development of several tissue types and that altered expression of ARID3B may contribute to cancer.
Pictured above is a representative images of immunohistochemistry from sections of normal ovarian epithelium, a benign tumor, and two malignant tumors. Brown staining indicates ARID3B protein. Blue staining is hematoxylin. We found that ARID3B is expressed in 82% of serous ovarian tumors that we examined. This suggests that this molecule may contribute to cancer.
*Cowden Dahl, K. D., Dahl, R., Kruichak, J. and Hudson, L. G. The EGFR responsive miR-125a represses mesenchymal morphology in ovarian cancer cells. Neoplasia. 11(11):1208-15.
* Corresponding Author
Cowden Dahl, K. D., Symowicz, J., Ning, Y., Gutierrez, E., Fishman, D. A., Adley B.P., Stack, M. S. and Hudson, L. G. Matrix metalloproteinase 9 is a mediator of epidermal growth factor-dependent E-cadherin loss in ovarian carcinoma cells. Cancer Research. 68(12): 4606-13.
Cowden Dahl, K. D., Zeineldin, R. and Hudson, L. G. (2007) PEA3 is necessary for optimal EGF receptor stimulated MMP expression and invasion of ovarian tumor cells. Molecular Cancer Research, 5 (5): 413-21.
Cowden Dahl, K. D., Fryer, B. H., Mack, F. A., Compernolle, V., Maltepe, E. Adelman, D. M., Carmeliet, P. and Simon, M. C. (2005)The Hypoxia-Inducible Factors regulate trophoblast differentiation. Mol Cell Biol, 25 (23): 10479-91.
Cowden Dahl, K. D., Robertson, S. E., Weaver, V. M., and Simon, M. C. (2005) Hypoxia-inducible factor regulates alphavbeta3 integrin cell surface expression. Mol Biol Cell, 16: 1901-1912.
Ramirez-Bergeron, D. L., Runge, A, Cowden Dahl, K. D., Fehling, H. J., Keller, G., and Simon, M.C. (2004) Hypoxia affects mesoderm and enhances hemangioblast specification during early development. Development. 131 (18):4623-34.
Cowden, K. D. and Simon, M. C. (2002) The bHLH/PAS factor MOP3 does not participate in hypoxia responses. Biochemical and Biophysical Research Communications. 290: 1228-1236.
Tan Nguyen (Technician)
Dr. Stancy Joseph (Postdoc)
Dr. Lynn Roy (Postdoc)
Serene Samyesudhas (Technician)