CMRC Children's Memorial Research Center

Dawn Kirschmann
 Research Associate Professor, Cancer Biology and Epigenomics Program

2300 Children's Plaza, Box 222
Room C.474
Chicago, IL 60614
Phone: (773) 755-6558
Fax: (773) 755-6594

Year Degree Institution
1995 Post Doctorate Monsanto Company (Pfizer)
1992 Ph.D. The Medical College of Pennsylvania
1987 B.S. Cook College, Rutgers University

Work Experience
Period Description Organization
2004 - Present Research Associate Professor, Department of Pediatrics, Northwestern University, Robert H. Lurie Comprehensive Cancer Center member Children's Memorial Research Center
1996 - 2004 Assistant Research Scientist, Department of Anatomy & Cell Biology, Holden Comprehensive Cancer Center member The University of Iowa
1995 - 1997 Visiting Scientist, Department of Immunology Monsanto Company (Pfizer)
1995 - 1996 Assistant Research Professor, Department of Pediatrics, Department of Internal Medicine, Division of Rheumatology, Saint Louis University Pediatric Research Institute

Research Interests
In 2003, the 5-year survival rate was 97% for patients with localized breast cancer. However, the 5-year survival rate for breast cancer patients with regional tumor invasion decreases to 78%, and to 23% for women with distant metastases. The decreased survival rates for women with regional invasion and distant metastases demonstrates our lack of understanding of breast cancer biology and disease progression, and accentuates the need for directed anti-invasive/metastatic therapeutic modalities. Therefore, it is critical to determine the molecular mechanism(s) of breast cancer metastasis (i.e. molecular markers that definitively distinguish tumors of non-metastatic potential from those with metastatic potential). To identify such invasion/metastasis-associated genes, we utilized differential display to compare mRNA expression in highly invasive/metastatic breast cancer cell lines to that expressed in poorly invasive/non-metastatic breast cancer cell lines. Using this technique we identified lysyl oxidase, which is up-regulated in invasive/metastatic breast cancer cells.
Lysyl oxidase (LOX) belongs to a family of copper-dependent amine oxidases that catalyze the oxidative deamination of peptidyl-lysine and hydroxylysine to reactive semialdehydes. Traditionally, LOX has been shown to initiate the covalent cross-linking of collagens and elastin in extracellular matrices. However, recent evidence suggests that LOX is a multifunctional or “moonlighting” protein. LOX has been shown to induce motility and migration in monocytes, vascular smooth muscle cells, and fibroblasts. In addition, a role for LOX in transcriptional gene regulation has been implicated as evidenced by localization of LOX protein and enzymatic activity to cell nuclei, utilization of histone H1 and H2 as substrates, and activation of the collagen III alpha1 promoter through LOX-induced binding of Ku antigen.
We have shown that LOX facilitates motility and invasion in breast cancer cells through a hydrogen peroxide-mediated mechanism, which activates the FAK/Src signaling pathway leading to the activation of Rac and Cdc42 (Rho GTPases). These results demonstrate that LOX facilitates breast cancer cell motilty by regulating actin filament formation. Our research continues to identify the extracellular and intracellular cues that modulate LOX expression and activity in invasive/metastatic breast cancer cells, including potential protein binding partners and novel enzymatic targets of LOX .

Lab Affiliations
M.J.C. Hendrix Research Laboratory
Recent Publications
Postovit, L.M., D.E. Abbott, S.L. Payne, W.W. Wheaton, N.V. Margaryan, R. Sullivan, M.K. Jansen, K. Csiszar, M.J.C. Hendrix and D.A. Kirschmann (In Press). Hypoxia reoxygenation: A dynamic regulator of lysyl oxidase-facilitated breast cancer migration. Journal of Cellular Biochemistry.

Payne, SL, Hendrix MJC, and Kirschmann, DA (August, 2007). Paradoxical roles for lysyl oxidases in cancer – A prospect. Journal of Cellular Biochemistry: 101:1338-1354.
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Payne, S.L., M.J.C. Hendrix, and D.A. Kirschmann. (July, 2006). Lysyl oxidase regulates actin filament formation through the p130Cas/Crk/DOCK180 signaling complex.. J. Cell. Biochem: 98:827-837.
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Payne, S.L., B. Fogelgren, A.R. Hess, E.A. Seftor, E.L. Wiley, S.F.T. Fong, K. Csiszar, M.J.C. Hendrix, and D.A. Kirschmann (December, 2005). Lysyl oxidase regulates breast cancer cell migration and adhesion through a hydrogen peroxide-mediated mechanism.. Cancer Res: 65:11429-11436.
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Kirschmann, D.A., E.A. Seftor, D.R.C. Nieva, C.M. Sullivan, E. Edwards, S.F.T. Fong, P. Sommer, K. Csiszar, and M.J.C. Hendrix (2002). A molecular role for lysyl oxidase in breast cancer invasion. Cancer Res.: 62:4478-4483.
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Kirschmann, D.A., E.A. Seftor, D.R.C. Nieva, E.A. Mariano, and M.J.C. Hendrix (1999). Differentially expressed genes associated with the metastatic phenotype in breast cancer. Breast Cancer Res. Treatment: 55:127-136.
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Recent Presentations
Kirschmann (2007). Lysyl oxidase mediates an epithelial to mesenchymal transition in breast cancer cell lines. Proc. 98th Ann. Meet. Am. Assn. Cancer Res. Los Angeles, CA.

Kirschmann (2006). Lysyl oxidase and breast cancer tumor progression. Children’s Memorial Research Center: Research Progress Reports. Chicago, IL.

Kirschmann (2003). Lysyl Oxidase Facilitates Motility in Breast Cancer. Laboratory of Matrix Pathology, University of Hawaii. Honolulu, HI.

Kirschmann (2001). A Molecular Role for Lysyl Oxidase in Breast Cancer Invasion. Laboratory of Matrix Pathology, University of Hawaii. Honolulu, HI.

2004 - Eisenberg Scholar, Children’s Memorial Research Center

1999 - University of Iowa Comprehensive Cancer Center Vere D. Wenger Travel Award

1999 - University of Iowa Florence Lindsay Young Investigator Award

1998 - American Journal of Pathology Cover Design: Hypothetical model for uveal melanoma dissemination.

1991 - Philadelphia chapter of the American Society of Microbiologists, Student poster

1990 - MCP Graduate Student Recognition Award, Honorable mention

1987 - Academic Achievements in Microbiology - Rutgers University

1987 - George H. Cook Research Scholar - Cook College, Rutgers University

Professional Service
2004 - Present CMRC Institutional Biosafety Committee
2004 - Present CMRC Chemical Safety Committee
2004 - Present Y-ME National Breast Cancer Organization, Illinois Affiliate, IlliNoisy Advocacy Committee
1996 - Present Intermittent Journal Referee: British Journal of Cancer, Cancer Research, Clinical Cancer Research, Clinical and Experimental Metastasis, Clinical and Experimental Metastasis, American Journal of Pathology, American Journal of Physiology: Lung, Cellular, and Molecular Pathology, Journal of Cell Biology, Biomed Central, Gastroenterology, Gene, International Journal of Cancer
2006 - 2006 Bear Necessities Pediatric Cancer Foundation Research Grant Committee
2005 - 2006 American Cancer Society, Illinois Division, Research Advisory Committee
2005 - 2006 DePaul University Institutional Biosafety Committee
2005 - 2005 Canadian Breast Cancer Research Alliance “New Approaches to Metastatic Disease Competition” grant review
2002 - 2004 California Breast Cancer Research Program "Tumor Progression" grant review
2003 - 2003 Ad hoc grant review for British International Research Council
2003 - 2003 VP for Research Internal Funding Initiative Committee grant review, The University of Iowa

Curriculum Vitae
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Last Updated: Jul 24 2007 3:07PM

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