University of Minnesota
MICaB Graduate Program
http://micab.umn.edu
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MICaB Faculty

Professor

Department of Laboratory Medicine and Pathology

Johns Hopkins, 1984, Ph.D.

612-625-5920 office
612-625-4942 lab

E-mail:skubi002@umn.edu


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

Recent Publications

  • Skubitz, A.P.N.,  Taras, E. P., Boylan, K.L.M., Waldron, N.N., Oh, S. Panoskaltsis-Mortari, A., and Vallera, D.A. (2013) Targeting CD133 in an in vivo ovarian cancer model reduces ovarian cancer progression.  Gynecologic Oncology 130:579-587.
  • Less, R., Boylan, K.L.M., Skubitz, A.P.N., and Aksan, A. (2013) Isothermal vitrification methodology development for non-cryogenic storage of archival human sera. Cryobiology 66:176-185.
  • Betsou, F., Gunter, E., Clements, J., De Souza, Y., Goddard, K.A.B., Guadagni, F., Yan, W., Skubitz, A., Somiari, S., Yeadon, T., and Chuaqui, R.  (2013) Identification of evidence-based biospecimen quality-control tools.  A report of the International Society for Biological and Environmental Repositories (ISBER) Biospecimen Science Working Group.  The Journal of Molecular Diagnostics 15: 3-16.
  • Mathay, C., Yan, W., Chuaqui, R., Skubitz, A., Jeon, J., Fall, N., Betsou, F., and Barnes, M. (2012) Short-term stability study of RNA at room temperature.  Biopreservation and Biobanking 10(6):532-542.
  • Unhale, S.A., Skubitz, A.P.N., Solomon, R., and Hubel, A.  (2012) Stabilization of tissue specimens for pathological examination and biomedical research.  Biopreservation and Biobanking 10(6):493-500.
  • Sueblinvong, T., Ghebre, R., Iizuka, Y., Pambuccian, S.E., Isaksson Vogel, R., Skubitz, A.P.N., and Bazzaro, M.  (2012) Establishment, characterization and downstream application of primary ovarian cancer cells derived from solid tumors. PLoS ONE 7(11): 1-9 (e50519).
  • Lehmann, S., Guadagni, F., Moore, H., Ashton, G., Barnes, M., Benson, E., Clements, J., Koppandi, I., Coppola, D., Demiroglu, S.Y., DeSouza, Y., De Wilde, A., Duker, J., Eliason, J., Glazer, B., Harding, K., Jeon, J.P., Kessler, J., Kokkat, T., Nanni, U., Shea, K., Skubitz, A., Somiari, S., Tybring, G., Gunter, E., and Betsou, F. (2012)  [International Society for Biological and Environmental Repositories (ISBER) Working Group on Biospecimen Science]  Standard preanalytical coding for biospecimens:  Review and implementation of the Sample PREanalytical Code (SPREC).  Biopreservation and Biobanking 10(4):366-374
  • Rizzardi, A.E., Johnson, A.T., Isaksson Vogel, R., Pambuccian, S.E., Henriksen J., Skubitz, A.P.N., Metzger, G.J., and Schmechel, S.C. (2012)  Quantitative comparison of immunohistochemical staining measured by digital image analysis versus pathologist visual scoring. Diagnostic Pathology 7:42.
  • Campbell, L.D. (Editor-in-Chief), Betsou, F., Garcia, D.L., Giri, J.G., Pitt, K.E., Pugh, R.S., Sexton, K.C., Skubitz, A.P.N., and Somiari, S.B. (Associate Editors) (2012) 2012 Best practices for repositories: Collection, storage, retrieval and distribution of biological materials for research. Third edition. Biopreservation and Biobanking 10(2): 79-161.
  • Skubitz, K.M., Francis P., Skubitz, A.P.N., Luo, X., and Nibert, M. (2012)  Gene expression identifies heterogeneity of metastatic propensity in high-grade soft tissue sarcomas. Cancer 118:4235-4243.
  • Nikas, J.B., Boylan, K.L.M., Skubitz, A.P.N., and Low, W.C. (2011)  Mathematical prognostic biomarker models for treatment response and survival in epithelial ovarian cancer.  Cancer Informatics 10: 233–247.
  • Hubel, A., Aksan, A., Skubitz, A.P.N., Wendt, C., and Zhong, X. (2011)  State of the art in preservation of fluid biospecimens.  Biopreservation and Biobanking 9:237-244.
  • Boylan, K.L.M., Misemer, B., DeRycke, M.S., Andersen, J.D., Harrington, K.M., Kalloger, S.E., Gilks, C.B., Pambuccian, S.E., and Skubitz, A.P.N.  (2011) Claudin 4 is differentially expressed between ovarian cancer subtypes and plays a role in spheroid formation.  International Journal of Molecular Sciences 12:1334-1358.
  • Andersen, J.D., Boylan, K.L.M., Jemmerson, R., Geller, M.A., Misemer, B., Harrington, K.M., Weivoda, S., Witthuhn, B.A., Argenta, P., Isaksson Vogel, R., and Skubitz, A.P.N.  (2010) Leucine-rich alpha-2-glycoprotein-1 is upregulated in sera and tumors of ovarian cancer patients.  Journal of Ovarian Research 3:21-34.
  • DeRycke, M.S., Pambuccian, S.E., Gilks, C.B., Kalloger, S.E., Ghidouche, A., Lopez, M., Bliss, R.L., Geller, M.A., Argenta, P.A., Harrington, K.M., Skubitz, A.P.N. (2010) Nectin 4 overexpression in ovarian cancer tissues and serum:  Potential role as a serum biomarker. American Journal of Clinical Pathology 134:835-845.
  • Boylan, K.L.M., Andersen, J.D., Anderson, L.B., Higgins, L., and Skubitz, A.P.N.  (2010) Quantitative proteomic analysis by iTRAQ® for the identification of candidate biomarkers in ovarian cancer serum. Proteome Science 8:31-40.
  • Skubitz, K.M., and Skubitz, A.P.N. (2010) Two new synthetic peptides from the N-domain of CEACAM1 (CD66a) stimulate neutrophil adhesion to endothelial cells. Biopolymers: Peptide Science 96(1):25-31.
  • Betsou, F., Lehmann, S., Ashton, G., Barnes, M., Benson, E.E., Coppola, D., DeSouza, Y., Eliason, J., Glazer, B., Guadagni, F., Harding, K., Horsfall, D.J., Kleeberger, C., Nanni, U., Prasad, A., Shea, K., Skubitz, A., Somiari, S., and Gunter, E. [International Society for Biological and Environmental Repositories (ISBER) Working Group on Biospecimen Science]  (2010)  Standard Preanalytical Coding for Biospecimens: Defining the Sample PREanalytical Code (SPREC). Cancer Epidemiology Biomarkers Prevention 19(4):1004-11.
  • Andersen, J.D., Boylan, K.L.M., Xue, F.S., Anderson, L.B., Witthuhn, B.A., Markowski, T.W., Higgins, L., and Skubitz, A.P.N. (2010) Identification of candidate biomarkers in ovarian cancer serum by depletion of highly abundant proteins and differential in-gel electrophoresis.  Electrophoresis 31:599-610.
  • DeRycke, M.S., Andersen, J.D., Harrington, K.M., Pambuccian, S.E., Kalloger, S.E., Boylan, K.L.M., Argenta, P.A., and Skubitz, A.P.N.  (2009) S100A1 expression in ovarian and endometrial endometrioid carcinomas is a prognostic indicator of relapse-free survival.  American Journal of Clinical Pathology 132:846-856.
  • Betsou, F., Barnes, R., Burke, T., Coppola, D., DeSouza, Y., Eliason, J., Glazer, B., Horsfall, D., Kleeberger, C., Lehmann, S., Prasad, A., Skubitz, A., Somiari, S., Gunter E. (2009). Human biospecimen research: Experimental protocol and quality control tools [International Society for Biological and Environmental Repositories (ISBER) Working Group on Biospecimen Science]. Cancer Epidemiology Biomarkers Prevention 18:1017-1025.
  • Skubitz, K.M., and Skubitz, A.P.N. (2008) Interdependency of CEACAM-1, -3, -6, and -8 induced human neutrophil adhesion to endothelial cells.  Journal of Translational Medicine 6:78.
  • Skubitz, K.M., Pambuccian, S.E., Manivel, J.J.C., and Skubitz, A.P.N.  (2008)  Identification of heterogeneity among soft tissue sarcomas by gene expression profiles from different tumors. Journal of Translational Medicine 6:23.
  • Pitt, K.E. (Editor-in-Chief), Campbell, L.D., Skubitz, A.P.N., Somiari, S.B., Sexton, K.C., and Pugh, R.S. (Associate Editors) (2008) 2008 Best practices for repositories:  Collection, storage, retrieval, and distribution of biological materials for research.  Second edition. Cell Preservation Technology 6(1):3-58.
  • Tchagang, A.B., Tewfik, A.H., DeRycke, M.S., skubitz, K.M., and Skubitz, A.P.N. (2008) Early detection of ovarian cancer using group biomarkers. Molecular Cancer Therapeutics 7:27-37.
  • Skubitz, A.P.N., Pambuccian, S.E., Argenta, P.A., and skubitz, K.M.  (2006) Differential gene expression identifies subgroups of ovarian carcinoma. Translational Research 148:223-248.