The Ewald Lab conducts both basic and translational related to the molecular regulation of collective cell migration during normal mammary development and during the invasion and metastatic spread of mammary tumors.
During his postdoctoral studies, Dr. Ewald studied the cellular basis of branching morphogenesis in the mammary gland. He demonstrated that normal mammary branching morphogenesis occurred through the generation of a high proliferation, low apico-basal polarity, high motility, transiently stratified epithelial intermediate. As this normal developmental process dynamically regulated many of the properties that are modulated during human breast tumor progression, he developed a series of related assays that enabled direct culture, observation and molecular manipulation of mouse models of mammary carcinoma, human mammary epithelium, and human mammary carcinomas.
The Ewald Lab uses advanced time-lapse microscopy and molecular genetics to study the normal development of tissues, with a primary focus on the mammary gland. His team is trying to understand the cellular and molecular processes that enable normal epithelial cells to progress to invasive and eventually metastatic breast cancer.
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Nguyen-Ngoc KV, Cheung KJ, Brenot A, Shamir ER, Gray RS, Hines WC, Yaswen P, Werb Z, Ewald AJ, “The ECM microenvironment regulates collective migration and local dissemination in normal and malignant mammary epithelium” Proc Natl Acad Sci U S A. 2012 Sep 25;109(39):E2595-604.
Beck JN, Singh A, Rothenberg AR, Elisseeff JH, Ewald AJ, “The independent roles of mechanical, structural and adhesion characteristics of 3D hydrogels on the regulation of cancer invasion and dissemination,” Biomaterials, 2013 Dec;34(37):9486-95.
Cheung KJ, Gabrielson E, Werb Z, Ewald AJ, “Collective invasion in breast cancer requires a conserved basal epithelial program,” Cell. 2013 Dec 19;155(7):1639-51.
Shamir ER, Papallardo E, Jorgens DM, Coutinho K, Tsai WT, Aziz K, Auer M, Tran PT, Bader JS, Ewald AJ, “Twist1-induced dissemination preserves epithelial identity and requires E-cadherin,” The Journal of Cell Biology. 2014 Mar 3;204(5):839-56.
Cheung KJ, Padmanaban VP, Silvestri V, Schipper K, Fairchild AN, Ewald AJ, “Distant metastasis occurs through collective epithelial dissemination,” PNAS, 2016 Feb 16;113(7):E854-63.