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

  • Yang, J.; Kasberg, W. C.; Celo, A.; Liang, Z.; Quispe, K.; Stack, M. S. "Post-translational modification of the membrane type 1 matrix metalloproteinase (MT1-MMP) cytoplasmic tail impacts ovarian cancer multicellular aggregate dynamics." J. Biol. Chem. 2017, 292, 13111-13121.
  • Sawe, R. T.; Mining, S. K.; Ofulla, A. V.; Patel, K.; Guyah, B.; Chumba, D.; Prosperi, J. R.; Kerper, M.; Shi, Z.; Sandoval-Cooper, M.; Taylor, K.; Badve, S.; Stack, M. S.; Littlepage, L. E. "Tumor infiltrating leukocyte density is independent of tumor grade and molecular subtype in aggressive breast cancer of Western Kenya." Trop. Med. Health 2017, 45, 19.
  • Klymenko, Y.; Kim, O.; Stack, M. S. "Complex Determinants of Epithelial: Mesenchymal Phenotypic Plasticity in Ovarian Cancer." Cancers 2017, 9, 104.
  • Klymenko, Y.; Johnson, J.; Bos, B.; Lombard, R.; Campbell, L.; Loughran, E.; Stack, M. S. "Heterogeneous Cadherin Expression and Multicellular Aggregate Dynamics in Ovarian Cancer Dissemination." Neoplasia 2017, 19, 549-563.
  • Asem, M. S.; Buechler, S.; Wates, R. B.; Miller, D. L.; Stack, M. S. "Wnt5a Signaling in Cancer." Cancers 2016, 8, 79.
  • Shah, S. S.; Senapati, S.; Klacsmann, F.; Miller, D. L.; Johnson, J. J.; Chang, H.; Stack, M. S. "Current Technologies and Recent Developments for Screening of HPV-Associated Cervical and Oropharyngeal Cancers." Cancers 2016, 8, 85.

Contact Information

  • Kleiderer-Pezold Professor of Biochemistry and Ann F. Dunne & Elizabeth Riley Director, Harper Cancer Research Institute
  • Send an email

Primary Research Areas

Research Specialties