Dr. Stack received her PhD degree in Biochemistry from the University of Louisville and completed post-doctoral training in biochemical pathology at Duke University Medical Center. She served as Research Assistant Professor in Pathology at Duke before joining the faculty in the Department of Cell & Molecular Biology at Northwestern University. In 2007 she joined the University of Missouri as Professor and Vice Chair for Research in the Department of Pathology and Anatomical Sciences. She joined the faculty at the University of Notre Dame in 2011 as Science Director of the Mike and Josie Harper Cancer Research Institute and professor of chemistry and biochemistry.
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.
Burkhalter R, Symowicz J, Hudson LG, Gottardi CJ and Stack MS (2011) Integrin regulation of beta-catenin signaling in ovarian carcinoma. J Biol Chem 286: 23467-75.
Ghosh S, Koblinski J, Johnson J, Liu Y, Frazier S, Ericcson A, Shi Z, Ravosa MJ, Crawford S and Stack MS (2010) Urinary-type plasminogen activator receptor/a3b1 integrin signaling and oral tumor progression. Mol Can Res 8:145-158.
Moss N.M., Barbolina M.V., Liu Y., Sun L., Munshi H.G., and Stack, M.S. "Ovarian Carcinoma Cell Detachment and Multi-cellular Aggregate Formation are Regulated by MT1-MMP: A Potential Role in Intra-Peritoneal Metastatic Dissemination." Cancer Research 2009; 69: 7121-9.
Hudson, L.G., Zeineldin, R., and Stack, M.S. "Phenotypic Plasticity of Neoplastic Ovarian Epithelium: Unique Cadherin Profiles in Tumor Progression." Clin. Exp. Metastasis 2008; 25: 643-655.
Jiang R, Shi Z, Johnson JJ, Liu Y, and Stack MS (2011) Kallikrein-5 promotes cleavage of desmoglein-1 and loss of cell-cell cohesion in oral squamous cell carcinoma. J Biol Chem 286: 9127-35.