Morris Pollard Collegiate Professor of Biological Sciences
University of Notre Dame
Cell Signaling and Cancer Progression
The early stages of cancer progression are tightly linked to alterations in signaling cascades that control cell adhesion and invasion. Research in our laboratory focuses on a signaling axis that facilitates these changes and appears to be deregulated in several human cancers. Current studies seek to identify key regulators of epithelial glandular disruption as well as tumor cell invasion. We are interested in delineating the impact of specific molecular alterations on cancer initiation and progression, with the ultimate goal of extending these findings to the development of new diagnostic and therapeutic platforms. Our research utilizes cell biological, molecular and biochemical approaches in cellular and organotypic model systems, coupled with interrogation of clinical samples and animal models. The acquisition of the invasive phenotype—when cells disrupt normal cell-cell contacts and acquire phenotypic alterations that permit invasion through the surrounding tissue—is the focus of the laboratory’s research.
Clancy JW, Sedgwick A, Rosse C, Muralidharan-Chari V, Raposo G, Method M, Chavrier P, D'Souza-Schorey C. (2015) Regulated delivery of molecular cargo to invasive tumour-derived microvesicles. Nature Communications. 6: 6919-6930
D'Souza-Schorey, C. and Di Vizio, D. (2014) Biology and proteomics of extracellular vesicles: harnessing their clinical potential. Expert Rev Proteomics.11:251-253.
Pellon-Cardenas O, Clancy J, Uwimpuhwe H, D'Souza-Schorey C. (2013) ARF6-Regulated Endocytosis of Growth Factor Receptors Links Cadherin-Based Adhesion to Canonical Wnt Signaling in Epithelia. Mol. Cell. Biol. 33:2963-2975.
Grossmann AH, Yoo JH, Clancy J, Sorensen LK, Sedgwick A, Tong Z, Ostanin K, Rogers A, Grossmann KF, Tripp SR, Thomas KR, D'Souza-Schorey C, Odelberg SJ, Li DY. (2013) The small GTPase ARF6 stimulates β-catenin transcriptional activity during WNT5A-mediated melanoma invasion and metastasis. Science Signaling. 6(265):ra14.
D'Souza-Schorey C, Clancy JW. (2012) Tumor-derived microvesicles: shedding light on novel microenvironment modulators and prospective cancer biomarkers. Genes and Development. 26: 1287-99.