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
2012
Elected Fellow, American Association for the Advancement of Science
2011
Ann F. Dunne and Elizabeth Riley Director, Harper Cancer Research Institute
2008
Mulligan Endowed Professor of Cancer Research, University of Missouri

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

  • Johnson, J.J.; Miller, D.L.; Jiang, R.; Liu, Y.; Shi, Z.; Tarwater, L.; Williams, R.; Balsara, R.; Sauter, E.R.; Stack, M.S. "Protease Activated Receptor-2 (PAR-2)-Mediated Nf-kB Activation Suppresses Inflammation-Associated Tumor Suppressor MicroRNAs in Oral Squamous Cell Carcinoma." J. Biol. Chem. 2016, 291(13), 6936-6945.

  • Liu, Y.; Metzinger, M.; Lewellen, K.; Cripps, S.N.; Carey, K.D.; Harper, E.I.; Shi, Z.; Tarwater, L.; Grisoli, A.; Lee, E.; Slusarz, A.; Yang, J.; Loughran, E.A.; Conley, K.; Johnson, J.J.; Klymenko, Y.; Bruney, L.; Liang, Z.; Dovichi, N.J.; Cheatham, B.; Leevy, W.M.; Stack, M.S. "Obesity Contributes to Ovarian Cancer Metastatic Success Through Increased Lipogenesis, Enhanced Vascularity, and Decreased Infiltration of M1 Macrophages." Cancer Res. 2015, 75, 5046-5057.

  • Burkhalter, R.J.; Westfall, S.D.; Liu, Y.; and Stack, M.S. "Lysophosphatidic Acid Initiates Epithelial to Mesenchymal Transition and Induces beta-Catenin-Mediated Transcription in Epithelial Ovarian Carcinoma." J. Biol. Chem. 2015, 290, 22143-22154.

  • Miller, D.L.; Davis, J.W.; Taylor, K.H.; Johnson, J.; Shi, Z.G.; Williams, R.; Atasoy, U.; Lewis, J.S.; Stack, M.S. "Identification of a Human Papillomavirus-Associated Oncogenic miRNA Panel in Human Oropharyngeal Squamous Cell Carcinoma Validated by Bioinformatics Analysis of The Cancer Genome Atlas." Am. J. Pathol. 2015, 185 (3), 679-692.

  • Bruney, L.; Conley, K.C.; Moss, N.M.; Liu, Y.Y.; Stack, M.S. "Membrane-type I matrix metalloproteinase-dependent ectodomain shedding of mucin16/CA-125 on ovarian cancer cells modulates adhesion and invasion of peritoneal mesothelium." Biol. Chem. 2014, 395 (10), 1221-1231.

  • Lengyel, E.; Burdette, J.E.; Kenny, H.A.; Matei, D.; Pilrose, J.; Haluska, P.; Nephew, K.P.; Hales, D.B.; Stack, M.S. "Epithelial ovarian cancer experimental models." Oncogene 2014, 33 (28), 3619-3633.

 

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