My primary research focus for most of the last 20 years has been the study of extracellular matrix (ECM) receptor signaling in the context of normal epithelial cell biology and cancer progression, using both cell culture and transgenic mouse models. My motivation has been to understand the mechanisms coordinating the development and function of cells within tissues, and to understand how alterations in these mechanisms contribute to diseases, such as cancers.
My laboratory’s efforts have revealed the roles of specific ECM proteins and receptors in the control of epithelial tissue architecture (apico-basal polarity) and growth. These studies highlighted the importance of ECM assembly and endocytic trafficking processes in the control of epithelial architecture and function. They have also provided insights into the alteration of these processes in cancers, revealing novel changes in post-translational protein modifications arising with cancer progression that lead to changes in ECM assembly and protein trafficking.
My studies of endocytic trafficking have sparked a strong interest in generating cancer-targeting agents and their value for selectively delivering therapeutic agents, or imaging agents, to the interior of cancer cells.
More recently, as a member of the Oregon Center for Spatial Systems Biomedicine (OCSSB) I have developed a strong interest in new methods of 3D cancer imaging in intact tissues using light sheet microscopy, and have been pioneering the application of these new tissue clearing, staining, and imaging technologies to the study of cancer progression.Read more
Areas of interest
- My research has focused on ECM receptor signaling in the context of normal cell biology and human disease, and the generation of unique reagents and methods for the dissection of these pathways.
Memberships and associations
- OHSU Center for Spatial System Biomedicine
Leonoudakis D, Huang G, Akhavan A, Fata JE, Singh M, Gray JW, Muschler JL. Endocytic trafficking of laminin is controlled by dystroglycan and is disrupted in cancers. J Cell Sci. 2014 Nov 15;127(Pt 22):4894-903. PubMed PMID: 25217627; PubMed Central PMCID: PMC4231305.
Leonoudakis, D., Singh, M., Mohajer, R., Mohajer, P., Fata, J.E., Campbell, K.P., Muschler, J.L. (2010). Dystroglycan controls signaling of multiple hormones through modulation of STAT5 activity. J. Cell Science.
Beliveau, A., Mott, J.D., Lo., A, Chen, E.I.2, Koller, A.A., Yaswen, P., Muschler, J.L. and Bissell, M.J. (2010) Raf-induced MMP9 Disrupts Tissue Architecture of Human Breast Cells in Three-Dimensional Culture and is Necessary for Tumor Growth in vivo. Genes and Development 24:2800-11.
Muschler, J.L., Streuli, C.H. (2010). Cell-matrix interactions in mammary gland development and breast cancer. In Mammary Gland Biology. Cold Spring Harb Perspect Biol doi: 10.1101/cshperspect.a003202.
Xu, R., Nelson, C.M., Muschler, J.L., Veiseh, M., Vonderhaar, B.K., Bissell, M.J. (2009). Sustained activation of STAT5 is essential for chromatin remodeling and maintenance of mammary-specific function. J. Cell Biology. 184:57-66.