Crislyn D'Souza-Schorey

Research Interests:

Our research lies at the intersection of two exciting disciplines in the life sciences, cell biology and molecular oncology. The most unfavorable events during the early stages of cancer progression are closely associated with alterations in cell adhesion, invasion, and intercellular communication within the tumor microenvironment. Our laboratory investigates the cellular mechanisms that facilitate these changes and are deregulated in several human cancers.

Within this framework, a key research focus is on the acquisition of the invasive phenotype, which occurs when cells disrupt normal cell-cell interactions and acquire phenotypes to facilitate invasion through surrounding tissue. We also seek to elucidate the mechanisms underlying cellular communication within microenvironments via extracellular vesicles. We investigate the processes that govern the formation of extracellular vesicles, extracellular vesicle-based paracrine signaling and intercellular communication, and translate our findings to the development of novel diagnostic and therapeutic platforms.

Biography:

• Department Chair, Biological Sciences, University of Notre Dame, IN 2014-2020
• Professor, Department of Biological Sciences, University of Notre Dame, IN 2011-Present
• Associate Professor, Department of Biological Sciences, University of Notre Dame, IN 2004-2011
• Assistant Professor, Department of Biological Sciences, University of Notre Dame, IN 1998-2004
• Research Assistant Professor, Department of Cell Biology, Washington University School of Medicine, St. Louis, MO 1997-1998
• Postdoctoral Fellow, Department of Cell Biology, Washington University School of Medicine, St. Louis, MO 1993-1996
• Ph.D. University of Texas Health Science Center at San Antonio, TX 1992

Selected Papers:

• D'Souza-Schorey C, Di Vizio D (2025) A class of large cell-like extracellular vesicles. Nature Cell Biology, 27: https://doi.org/10.1038/s41556-025-01611-2
• Schmidtmann M, Elliott V, Clancy J, Nakshatri H, D’Souza-Schorey C (2024) Ancestry-linked stromal variations impact breast epithelial cell invasion. bioRxiv, 12: 26.630400
• Caller T, Rotem I, Shaihov-Teper O, Lendengolts D, Schary Y, Shai R, Glick-Saar E, Dominissini D, Motiei M, Katzir I, Popovzter R., Boomgarden A, D'Souza-Schorey C, Naftali-Shani N. Leor J. (2024) Small extracellular vesicles from infarcted and failing heart accelerate tumor growth. Circulation 149:1729–1748. doi: 10.1161/CIRCULATIONAHA.123.066911
• Clancy JW, Sheehan C, Boomgarden A., D'Souza-Schorey C. (2022) Recruitment of DNA to tumor microvesicles. Cell Reports 38: 110443. doi.org/10.1016/j.celrep.2022.110443
• Clancy, JW, Boomgarden, AC. & D’Souza-Schorey, C. (2021) Profiling and promise of supermeres. Nature Cell Biology doi: 10.1038/s41556-021-00808-5
• Boomgarden AC, Clancy JW, D'Souza-Schorey C. (2020) Breaking Bad: Extracellular Vesicles Provoke Tumorigenic Responses Under Oxygen Deprivation. Developmental Cell. 55:111 doi: 0.1016/j.devcel.2020.09.027
• Howe, E.N., Burnette, M.D., Justice, M.E., Schnepp, P.M., Hedrick, V., Clancy, J.W., Guldner, I.H., Lamere, A.T., Li, J., Aryal, U.K., D’Souza-Schorey, C., Zartman, J.J., Zhang, S. (2020) Rab11b-mediated integrin recycling promotes brain metastatic adaptation and outgrowth. Nature Communications. 11, 3017 doi: 10.1038/s41467-020-16832-2
• Clancy JW, Zhang Y, Sheehan C, D'Souza-Schorey C. (2019) An ARF6-Exportin-5 axis delivers pre-miRNA cargo to tumour microvesicles. Nature Cell Biology 21:856 doi: 10.1038/s41556-019-0345-y.
• Sedgwick AE, D'Souza-Schorey C. (2016) Wnt Signaling in Cell Motility and Invasion: Drawing Parallels between Development and Cancer. Cancers. 8(9). pii: E80. doi: 10.3390/cancers8090080.
• 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.
• 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. doi: 10.1126/scisignal.2003398.
• 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.
• Tushir J.S., Clancy J., Warren A., Wrobel C., Brugge J.S., D'Souza-Schorey C. (2010) Unregulated ARF6 activation in epithelial cysts generates hyperactive signaling endosomes and disrupts morphogenesis. Mol. Biol. Cell. 21: 2355-2366.
• Muralidharan-Chari, V., Clancy J.W., Plou C., Romao M., Chavrier P, Raposo G., and D'Souza-Schorey C. (2009) “ARF6 regulated shedding of tumor-derived plasma membrane microvesicles.” Current Biology 19(22):1875-85.
• Muralidharan-Chari V., Hoover H., Clancy J., Schweitzer J., Suckow M., Schroeder V., Castellino F., Schorey J., D’Souza-Schorey C. (2009) ADP-ribosylation factor 6 regulates tumorigenic and invasive properties in vivo. Cancer Research 69: 2201-2209.
• Tushir, J.S. and D’Souza-Schorey C. (2007) ARF6-dependent activation of ERK and Rac1 modulates epithelial tubule development. EMBO J. 26: 1806-1819.
• D’Souza-Schorey C and Chavrier P. (2006) ARF proteins: roles in membrane traffic and beyond. Nature Reviews Mol. Cell. Biol. 7: 347-358.
• D’Souza-Schorey C. (2005) Disassembling adherens junctions: Breaking up is hard to do. Trends. Cell. Biol. 15: 19-26.
• Tague S., Muralidharan V., and D’Souza-Schorey C. (2004) ARF6 regulates tumor cell invasion via the activation of the MEK/ERK signaling pathway. Proc. Natl. Acad. Sci. 101: 9671-9676.
• Muchowski P., Ning K., D’Souza-Schorey C., and Fields S.F. (2002) Requirement of an intact microtubule cytoskeleton for aggregation of huntingtin exon 1. Proc. Natl. Acad. Sci, USA 99: 727-732.
• Peters P, Ning K., Palacios F., Kazantsez A., Thompson L., Bates G., and D’Souza-Schorey C. (2002) Arfaptin 2 regulates the aggregation of mutant huntingtin. Nature Cell Biology 4: 240-245.
• Palacios F., Schweitzer J., Boshans R.L. and D’Souza-Schorey, C. (2002) ARF6-GTP recruits nm23-H1 to facilitate dynamin-dependent endocytosis during adherens junction disassembly. Nature Cell Biology 4: 929-936.
• Palacios F., Price L., Schweitzer J., Collard J., and D’Souza-Schorey, C. (2001) An essential role for ARF6-regulated membrane traffic in adherens junction assembly and epithelial cell migration. EMBO J. 20: 4973-4986.
• Van Aelst L. and D’Souza-Schorey C. (1997) Rho GTPases and signaling networks. Genes and Development 11: 2295-2322.
• D’Souza-Schorey C., Li G., Colombo M.I., and Stahl P.D. (1995) A regulatory role for ARF6 in receptor-mediated endocytosis. Science 267: 1175-1178.

Primary Research Areas:

Cancer
Cellular & Molecular Biology
Development & Regeneration

Research Specialties:

ARF6 and other Ras-related GTPases
Cell Signaling
Cell Motility and Invasion
Cancer Biomarkers
Epithelial to Mesenchymal transitions
Extracellular Vesicles
Intercellular Adhesion and Communication
Membrane Trafficking
Metastasis