Research Programs: Tumor Biology and Progression, Women's Cancer
Professor, Department of Laboratory Medicine and Pathology

skubi002@umn.edu
612-625-5920 — office
612-625-4942 — lab
Preferred contact method: e-mail

Dr. Skubitz received her Ph.D. in Pharmacology and Experimental Therapeutics at The Johns Hopkins University School of Medicine in 1984. She conducted her postdoctoral work at the University of Minnesota Medical School in the Department of Laboratory Medicine and Pathology from 1984-1988 and subsequently joined the faculty of that department.

Research Interests

Ovarian cancer; diagnostic markers; cell-cell interactions

Dr. Skubitz's research is focused on the interaction of ovarian cancer cells with adhesion molecules present in the extracellular matrix and elsewhere, as well as with cell-cell interactions. We are interested in determining how ovarian cancer spreads, its genetic profile, and new biomarkers. Ovarian epithelial cancer cells do not adhere normally to the basement membrane; rather, they release from the basement membrane, seed other sites, develop into an ascitic form, or invade into the stroma of the ovary. We have shown that the more aggressive behavior of the malignant ovarian carcinoma cells, compared to normal ovarian epithelial cells, correlates with alterations in laminin receptors, in particular the a6b4 integrin. We have defined a mechanism whereby ovarian carcinoma cells adhere to mesothelial cells that line the peritoneal cavity, and then invade into the underlying tissues. We have discovered that the b1 integrin subunits and CD44 on the surface of ovarian carcinoma cells interact with mesothelial cells and their associated extracellular matrix, thereby promoting ovarian carcinoma cell adhesion and migration. We have shown that these same molecules play a role in promoting the invasion, spreading, and proliferation of ovarian carcinoma cells in vitro using single cells, multicellular aggregates or spheroids, and ovarian cancer cells isolated from the ascites fluid of patients. In order to identify novel biomarkers and/or therapeutic targets for ovarian cancer, as well as other types of cancer, we have analyzed Affymetrix gene microarray expression data and discovered many genes to be differentially expressed between cancer tissues and their normal tissue counterparts. In the case of the ovarian cancer genes, we have validated the data by immunohistochemistry and identified several potential biomarkers. Furthermore, we have been making strides to identify novel serum biomarkers that will ultimately improve the diagnostic assays for ovarian cancer. Namely, we are using the complementary proteomic techniques of DIGE, iTRAQ, and mass spectrometry protein profiling to discover proteins that are differentially expressed in the blood of ovarian cancer patients compared to the blood of control women. In summary, these research studies represent an approach toward understanding the molecular mechanisms modulating the phenotypic behavior of cancer cells and potentially aid in designing biomarkers and/or biopharmaceuticals for therapeutic use in cancer.

Selected Publications

Casey RC, Burleson KM, Skubitz KM, Pambuccian SE, Oegema TR Jr, Ruff LE, Skubitz AP. b1-integrins regulate the formation and adhesion of ovarian carcinomamulticellular spheroids. Am J Pathol. 2001;159:2071-2080.

Skubitz KM, Skubitz APN. Differential gene expression in renal-cell cancer. J Lab Clin Med. 2002;140:52-64.

Casey RC, Oegema TR Jr, Skubitz KM, Pambuccian SE, Grindle SM, Skubit AP. Cell membrane glycosylation mediates the adhesion, migration, and invasion of ovarian carcinoma cells. Clin Exp Metastasis. 2003;20:143-152.

Skubitz KM, Skubitz AP. Differential gene expression in leiomyosarcoma. Cancer. 2003;98:1029-1038.

Casey RC, Koch KA, Oegema TR Jr, Skubitz KM, Pambuccian SE, Grindle SM, Skubitz AP. Establishment of an in vitro assay to measure the invasion of ovarian carcinoma cells through mesothelial cell monolayers. Clin Exp Metastasis. 2003;20:343-356.

Skubitz KM, Skubitz AP. Differential gene expression in uterine leiomyoma. J Lab Clin Med. 2003;141:297-308.

Burleson KM, Casey RC, Skubitz KM, Pambuccian SE, Oegema TR Jr, Skubitz AP. Ovarian carcinoma ascites spheroids adhere to extracellular matrix components and mesothelial cell monolayers. Gyn Onc. 2004;93:170-181.

Burleson KM, Hansen LK, Skubitz AP. Ovarian carcinoma spheroids disaggregate on type I collagen and invade live human mesothelial cell monolayers. Clin Exp Metastasis. 2004;21(8):685-97.

Skubitz KM, Cheng EY, Clohisy DR, Thompson RC, Skubitz AP. Gene expression in giant-cell tumors. J Lab Clin Med. 2004.144:193-200.

Skubitz KM, Skubitz AP. Characterization of sarcomas by means of gene expression. J Lab Clin Med. 2004;144:78-91.

Hibbs K, Skubitz KM, Pambuccian S, Casey RC, Burleson KM, Oegema TR Jr, Thiele JJ, Grindle SM, Bliss R, Skubitz AP. Differential gene expression in ovarian carcinoma: Identification of potential biomarkers. Am J Path. 2004;165:397-414.

Burleson KM, Casey RC, Skubitz KM, Pambuccian SE, Oegema TR Jr, Skubitz AP. Ovarian carcinoma ascites spheroids adhere to extracellular matrix components and mesothelial cell monolayers. Gynecol Oncol. 2004;93:170-181.

Skubitz KM, Skubitz AP. Gene expression in aggressive fibromatosis. J Lab Clin Med. 2004;143:89-98.

Iida J, Skubitz AP, McCarthy JB, Skubitz KM. Protein kinase activity is associated with CD63 in melanoma cells. J Transl Med. 2005;3:42-50.

Skubitz KM, Cheng EY, Clohisy DR, Thompson RC, Skubitz AP. Differential gene expression in liposarcoma, lipoma, and adipose tissue. Cancer Invest. 2005;23:105-118.

Burleson KM, Boente MP, Pambuccian SE, Skubitz AP. Disaggregation and invasion of ovarian carcinoma ascites spheroids. J Transl Med. 2006;4:6.

Skubitz KM, Zimmerman W, Kammerer R, Pambuccian S, Skubitz AP. Differential gene expression identifies subgroups of renal cell carcinoma. J Lab Clin Med. 2006;147:250-267.

Skubitz AP, Pambuccian SE, Argenta PA, Skubitz KM. Differential gene expression identifies subgroups of ovarian carcinoma. Transl Res. 2006;148:223-248.

Tchagang AB, Tewfik AH, DeRycke MS, Skubitz KM, Skubitz AP. Early detection of ovarian cancer using group biomarkers. Mol Cancer Ther. 2008;7:27-37.