Research Summary
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.
Lab
The Ewald Lab seeks to elucidate the molecular regulation of collective cell migration during normal mammary development and during the invasion and metastatic spread of mammary tumors. The lab provides interdisciplinary training in both basic and translation aspects of cancer research. Dr. Ewald has an interdisciplinary training history and provides an interdisciplinary training environment.
Dr. Ewald originally trained in solid-state physics, which he then applied in his Ph.D. to develop and apply advanced light microscopy techniques to study the molecular regulation of tissue movements during embryonic development.
During his postdoctoral studies he extended this foundation in developmental biology and microscopy to study 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.
His laboratory works on isolating the molecular regulators of epithelial invasion and dissemination in these 3D assays, using a combination of knockdown and knockout genetics and advanced molecular imaging. Trainees benefit from dual training in epithelial development and epithelial cancer invasion and learn state-of-the-art molecular genetics, 3D organotypic culture, and imaging techniques. Members of the lab range from biomedical engineers through cell and molecular biologists to medical oncology fellows and benefit from collaborations with faculty in Biomedical Engineering, Medical Oncology, Radiation Oncology and Pathology.
Selected Publications
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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.
