M. Sharon Stack, PhD
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Professor and Vice Chair for Research
phone: 573-884-7301 (office); 573-884-2093 (lab)
email: stackm@missouri.edu
web: www.stackscientific.com
Biographical sketch
Research Area: Regulation of Metastasis-Associated Proteinases
Degrees:
BS, Clemson University, Biochemistry, 1981
MS, East Tennessee State Univ., Biomedical Sciences, 1985
PhD, University of Louisville, Biochemistry 1989
Additional study:
Post-doctoral Fellowship, Duke University (1989-1991)
Academic appointments:
Mulligan Professor of Cancer Research, University of Missouri (2008)
Professor & Vice Chair for Research, Pathology & Anatomical Sciences, University of Missouri (2007-present)
Adjunct Professor of Medical Physiology & Pharmacology, University of Missouri (2007-present)
Assistant/Associate/Professor of Cell & Molecular Biology, Northwestern University Medical School (1994-2007)
Research Assistant Professor of Pathology, Duke University (1991-1994)
Interests:
- proteinase regulation
- cell-cell and cell-matrix adhesion
- ovarian and oral tumors
- mechanotransduction
- extracellular matrix remodeling
Research description
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 Missouri) focuses on the relationship between mechanical loading and tissue remodeling in development and ageing of the masticatory apparatus.
Representative Publications:
- Ghosh, S., Johnson J.J., Sen, R., Mukhopadhyay S., Liu, Y., Zhang, F., Wei, Y., Chapman, H.A., and Stack, M.S. (2006) Functional Relevance of Urinary-type Plasminogen Activator Receptor (uPAR)-alpha3beta1 Integrin Association in Proteinase Regulatory Pathways. J. Biol. Chem. 281:13021-9.
- Ravosa, M.J., Kunwar, R., Stock, S.R. & Stack, M.S. (2007) Pushing the limit: Masticatory stress and adaptive plasticity in mammalian craniomandibular joints. J. Exp. Biol. 210:628-41.
- Barbolina, M.V., Ariztia, E.V., Adley, B.P., Liu, Y., and Stack, M.S. (2007) Microenvironmental Regulation of Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) Activity in Ovarian Carcinoma Cells via Collagen-Induced Egr-1 Expression. J. Biol. Chem. 282:4924-31.
- Symowicz, J.E., Adley, B.P., Gleason, K., Fishman, D.A., Hudson, L.G. and Stack, M.S. (2007) Integrin Engagement Promotes Proteinase-Dependent E-Cadherin Ectodomain Shedding in Ovarian Carcinoma Cells. Cancer Research 67: 2030-9.
- Shi, Z., and Stack, M.S. (2007) Urinary-Type Plasminogen Activator (uPA) and its Receptor (uPAR) in Squamous Cell Carcinoma of the Oral Cavity. Biochemical Journal 407:153-9.
- Hudson, L.G., Zeineldin, R., and Stack, M.S. (2008) Phenotypic Plasticity of Neoplastic Ovarian Epithelium: Unique Cadherin Profiles in Tumor Progression. Clin. Exp. Metastasis, 25: 643-655.
- Moss N.M., Barbolina M.V., Liu Y., Sun L., Munshi H.G., and Stack, M.S. (2009) Ovarian Carcinoma Cell Detachment and Multi-cellular Aggregate Formation are Regulated by MT1-MMP: A Potential Role in Intra-Peritoneal Metastatic Dissemination. Cancer Research 69: 7121-9.
- Moss, N.M., Liu, Y., Johnson, J.J., Debiase P., Jones J., Hudson, L.G., Munshi H.G., and Stack, M.S. (2009) Epidermal Growth Factor Receptor-Mediated Membrane Type 1 Matrix Metalloproteinase Endocytosis Regulates the Transition Between Invasive and Expansive Growth in Three-Dimensional Collagen. Molecular Cancer Research 7:809-820.
- Pettus, J., Johnson, J.J., Shi, Z., Davis, J.W., Koblinski, J.K., Ghosh, S., Liu, Y., Ravosa, M.J., Frazier, S. and Stack, M.S. (2009) Multiple Kallikrein (5, 7, 8, and 10) Expression in Squamous Cell Carcinoma of the Oral Cavity. Histology & Histopathology 24:197-207.
Book:
Cancer Treatment and Research: Ovarian Cancer. M.S. Stack & D.A. Fishman, Editors. Springer, 2nd Edition, 2009.
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