Sharon Stack

Sharon Stack

Regulation of Proteolysis and Adhesion

Biography

2011-present
Professor and Director, Harper Cancer Research Institute, University of Notre Dame
2007-2011
Professor and Vice-Chair for Research,University of Missouri School of Medicine
2006-2007
Professor, Northwestern University Medical School
2000-2006
Associate Professor, Northwestern University Medical School
1994-2000
Assistant Professor, Northwestern University Medical School
1991-1994
Assistant Research Professor, Duke University Medical Center
1989-1991
Postdoctoral Research Associate, Duke University Medical Center
1989
Ph.D. in Biochemistry, University of Louisville
1985
M.S. in Biomedical Sciences/Biochemistry, East Tennessee State University
1981
B.S. in Biochemistry, Clemson University

Selected Awards

2015
Juan Garcia Lifetime Achievement Award, American Cancer Society Lakeshore Division
2014
Herbert Fanger Lecture Honoree, Brown University
2014
Provost's Faculty Recognition Award
2012
Fellow, American Association for the Advancement of Science

Research Interests

The ability to invade host tissues and metastasize is the major cause of cancer-related death. During tumor invasion, metastasizing cells disrupt normal cell-cell and cell-matrix contacts and acquire a migratory, invasive phenotype. Thus modulation of cell-cell and cell-matrix adhesive events likely plays a critical role in tissue remodeling during tumor progression. Subsequent alterations in cellular architecture mediated by modified extracellular matrix (ECM) attachments induce expression of proteinases that degrade ECM proteins, facilitating migration through the modified tissue to establish metastatic foci and removing matrix constraints that normally limit proliferation. Although malignant cells produce a spectrum of matrix-degrading enzymes, predominant among these proteinases are enzymes in the plasminogen activator (PA) and matrix metalloproteinase (MMP) families. Current research centers on regulation of these proteinase families in two model systems: epithelial ovarian carcinoma and squamous cell carcinoma of the oral cavity. Ongoing research utilizes an integrative approach involving examination of 2-dimensional (2D) and 3D tissue culture systems and organotypic cultures complemented by murine tumor models and analyses of human tumors. Understanding the molecular mechanisms by which tumor cells orchestrate multiple microenvironmental cues to regulate the expression and activity of metastasis-associated proteinases is the major focus of the laboratory.

Additional collaborative research with Dr. Laurie Hudson (Univ. of New Mexico) is examining areas of convergence between epidermal growth factor receptor (EGFR) and cell adhesion (cadherin and integrin) signaling pathways in ovarian carcinoma metastatic dissemination. Collaborative research with Dr. Matthew Ravosa (Univ. of Notre Dame) focuses on the relationship between mechanical loading and tissue remodeling in development and ageing of the masticatory apparatus.

Recent Papers

  • Tang, J., Pulliam, N., Ozeş, A., Buechlein, A., Ding, N., Keer, H., Rusch, D., O'Hagan, H., Sharon Stack, M., Nephew, K.P. "Epigenetic targeting of adipocytes inhibits high-grade serous ovarian cancer cell migration and invasion" 2018 Molecular Cancer Research, 16 (8), pp. 1226-1240. DOI: 10.1158/1541-7786.MCR-17-0406
  • Harper, E.I., Sheedy, E.F., Stack, M.S. "With great age comes great metastatic ability: Ovarian cancer and the appeal of the aging peritoneal microenvironment" 2018 Cancers, 10 (7), 230. DOI: 10.3390/cancers10070230
  • Loughran, E.A., Leonard, A.K., Hilliard, T.S., Phan, R.C., Yemc, M.G., Harper, E., Sheedy, E., Klymenko, Y., Asem, M., Liu, Y., Yang, J., Johnson, J., Tarwater, L., Shi, Z., Leevy, M., Ravosa, M.J., Stack, M.S. "Aging Increases Susceptibility to Ovarian Cancer Metastasis in Murine Allograft Models and Alters Immune Composition of Peritoneal Adipose Tissue" 2018 Neoplasia (United States), 20 (6), pp. 621-631. DOI: 10.1016/j.neo.2018.03.007
  • Drakes, M.L., Mehrotra, S., Aldulescu, M., Potkul, R.K., Liu, Y., Grisoli, A., Joyce, C., O'Brien, T.E., Stack, M.S., Stiff, P.J. "Stratification of ovarian tumor pathology by expression of programmed cell death-1 (PD-1) and PD-ligand- 1 (PD-L1) in ovarian cancer" 2018 Journal of Ovarian Research, 11 (1), 43. DOI: 10.1186/s13048-018-0414-z​​​​​​​
  • Feist, P.E., Loughran, E.A., Stack, M.S., Hummon, A.B. "Quantitative proteomic analysis of murine white adipose tissue for peritoneal cancer metastasis" 2018 Analytical and Bioanalytical Chemistry, 410 (5), pp. 1583-1594. DOI: 10.1007/s00216-017-0813-9
  • Leonard, A.K., Loughran, E.A., Klymenko, Y., Liu, Y., Kim, O., Asem, M., McAbee, K., Ravosa, M.J., Stack, M.S. "Methods for the visualization and analysis of extracellular matrix protein structure and degradation" 2018 Methods in Cell Biology, 143, pp. 1-39. DOI: 10.1016/bs.mcb.2017.08.005

Contact Information

  • Kleiderer-Pezold Professor of Biochemistry; Ann F. Dunne & Elizabeth Riley Director, Harper Cancer Research Institute
  • Office: A200D Harper Hall
  • Phone: 574-631-2518
  • Send an email
  • Visit Website

Primary Research Areas

Research Specialties