- Professor and Director, Harper Cancer Research Institute, University of Notre Dame
- Professor and Vice-Chair for Research,University of Missouri School of Medicine
- Professor, Northwestern University Medical School
- Associate Professor, Northwestern University Medical School
- Assistant Professor, Northwestern University Medical School
- Assistant Research Professor, Duke University Medical Center
- Postdoctoral Research Associate, Duke University Medical Center
- Ph.D. in Biochemistry, University of Louisville
- M.S. in Biomedical Sciences/Biochemistry, East Tennessee State University
- B.S. in Biochemistry, Clemson University
- Juan Garcia Lifetime Achievement Award, American Cancer Society Lakeshore Division
- Elected Fellow, American Association for the Advancement of Science
- Ann F. Dunne and Elizabeth Riley Director, Harper Cancer Research Institute
- Mulligan Endowed Professor of Cancer Research, University of Missouri
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.
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.