Extracellular proteases can degrade extracellular matrix proteins and reshape the tissue microenvironment as well as cleave and activate signaling molecules such as growth factors and their receptors. These processes are essential for normal physiological tissue development, remodeling, and repair. On the flip side, tissue malfunction and tissue destruction due to dysregulated extracellular proteolysis characterize many pathological conditions including cancer. Extracellular proteolytic processes are critically involved in tumor growth, invasion, and dissemination of cancer cells to other organs. We are particularly interested in a family of cell-surface-anchored proteases: the type II transmembrane serine proteases (TTSPs) and their role in tissue remodeling during epithelial development and carcinogenesis. Understanding the physiological role of extracellular proteases in tissue development and homeostasis is important in order to pinpoint how dysregulated proteolysis can cause or contribute to cancer progression. The motivation behind parallel investigations of normal physiology and pathology is the idea that carcinogenesis often involves pathways, including proteolytic pathways, that are important in normal development and have gone awry in cancer. Generation and characterization of mouse models, including models of human breast and prostate cancer, play an integral role in our research. We use knock-out and transgenic mice for selected extracellular proteases and protease inhibitors as unique tools to identify critical proteolytic pathways in health and disease.
Murray AS, Varela FA, Hyland TE, Schoenbeck AJ, White JM, Tanabe LM, Todi SV, List K. Phosphorylation of the type II transmembrane serine protease, TMPRSS13 in Hepatocyte Growth Factor Activator Inhibitor-1 and 2-mediated cell surface localization.J Biol Chem. 2017.
Tanabe LM, List K. The role of type II transmembrane serine protease-mediated signaling in cancer. FEBS J. 2017;284:1421-36.
Zoratti GL, Tanabe LM, Hyland TE, Duhaime MJ, Colombo É, Leduc R, Marsault E, Johnson MD, Lin CY, Boerner J, Lang JE, List K. Matriptase regulates c-Met mediated proliferation and invasion in inflammatory breast cancer. Oncotarget. 2016;7:58162-73.
Murray AS, Varela FA, List K. Biol Chem. Type II transmembrane serine proteases as potential targets for cancer therapy. 2016; 397:815-26.
Zoratti GL, Tanabe LM, Varela FA, Murray AS, Bergum C, Colombo É, Lang JE, Molinolo AA, Leduc R, Marsault E, Boerner J, List K. Targeting matriptase in breast cancer abrogates tumour progression via impairment of stromal-epithelial growth factor signalling. Nat Commun. 2015; 6:6776.
Education and Training
Ph.D. (2000) University of Copenhagen, Denmark
Postdoctoral training: NIH/NIDCR, Bethesda, Maryland
Cancer Biology Courses Taught:
CB7210 Fundamentals of Cancer Biology
CB7700 Recent Developments in Cancer Biology