Dr. Andrew Ewald
Assistant Professor, Department of Cell Biology (Primary)
Assistant Professor, Department of Oncology (Secondary)
Member, Center for Cell Dynamics
Member, Sidney Kimmel Comprehensive Cancer Center, Breast Cancer Research Program
Member, Biochemistry, Cell and Molecular Biology Graduate Program
- B.S. in Physics with Honors, Haverford College - Ph.D. in Biochemistry and Molecular Biophysics, California Institute of Technology
- Embryology Course, Marine Biological Laboratory
- Postdoctoral Research in Epithelial Biology and Breast Cancer, University of California, San Francisco
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.
1. Song S, Ewald, AJ, Stallcup B. Werb, Z. and G. Bergers, "PDGFRb+ perivascular progenitor cells in tumors regulate pericyte differentiation and vascular survival", Nature Cell Biology, 2005, Sep; 7(9) :870-9.
2. Yu, W, Fang, X, Ewald, AJ, Hunt, A, Werb, Z, Mathay, M, Mostov, K, "Formation of cysts by alveolar type II cells in three-dimensional culture reveals a novel mechanism for epithelial morphogenesis", Molecular Biology of the Cell, 2007, May; 18: 1693-1700.
3. Fata, J, Mora, H, Ewald, AJ, Zhang, H, Yao, E, Werb, Z, Bissell, M, "The MAPK ERK-1,2 pathway integrates distinct and antagonistic signals from TGFa and FGF7 in morphogenesis of mouse mammary epithelium", Developmental Biology, 2007, Jun 1; 306(1):193-207.
4. Page-McCaw*, A, Ewald*, AJ, Werb, Z, "Matrixmetalloproteinases and the regulation of tissue remodeling", Nature Reviews Molecular Cell Biology, 2007, Mar; 8(3): 221-33. * = Co-First Authors
5. Kouros-Mehr, H, Bechis, SK, Slorach, EM, Littlepage, LE, Egeblad, M, Ewald, AJ, Pai, SY, Ho, IC, Werb, Z, "Gata-3 links tumor differentiation and dissemination in a luminal breast cancer model", Cancer Cell, 2008, Feb; 13(2): 141-52.
6. Ewald, AJ, Brenot, A, Duong, M, Chan, BC, Werb, Z, "Collective epithelial migration and cell rearrangements drive mammary branching morphogenesis", Developmental Cell, 2008 Apr; 14(4): 570-81.
7. Martin-Belmonte, H, Yu, W, Rodriguez-Fraticelli, AE, Ewald, AJ, Werb, Z, Alonso, MA, Mostov, K, "Cell polarity dynamics controls the mechanism of lumen formation in epithelial morphogenesis", Current Biology. 2008 Apr 8; 18(7): 507-13.
8. Lu, PF, Ewald, AJ, Werb, Z, Martin, G, "Genetic mosaic analysis reveals FGF receptor 2 is required in terminal end buds during mammary gland branching morphogenesis",Developmental Biology, 2008 Sep 1; 321(1):77-87.
9. Egeblad*, M, Ewald*, AJ, Asketraud, HA, Truitt, M, Welm, B, Bainbridge, E, Peeters, G, Krummel, M, Werb, Z, "Imaging stromal cells in intact tumor microenvironments", Disease Models and Mechanisms. 2008 Sep/Oct; 1(2/3): 155-67. * = Co-First Authors.
10. Andrew, DJ and Ewald, AJ, "Morphogenesis of epithelial tubes: Insights into tube formation, elongation, and elaboration", Developmental Biology, 2010 May 1;341(1):34-55. *Co-Corresponding Author
11. Ewald, AJ, Werb, Z, Egeblad, M, "Dynamic, Long-Term, In Vivo Imaging of Tumor-Stroma Interactions in Mouse Models of Breast Cancer Using Spinning-Disk Confocal Microscopy," Chapter 23, Live Cell Imaging, 2nd Edition, Edited by Robert Goldman, Jason Swedlow, and David Spector, Cold Spring Harbor Laboratory Press, 2010.
12. Gray, R.S., Cheung, K.J., Ewald, A.J., "Cellular mechanisms regulating epithelial morphogenesis and cancer invasion", Curr Opin Cell Biol. 2010 Oct;22(5):640-50.
13. Ewald, AJ, "Imaging the Cell Behavioral Basis of Branching Morphogenesis in 3D Organotypic and Whole Organ Cultures", Imaging in Developmental Biology, A Laboratory Manual,2nd Edition, Edited by James Sharpe and Rachel Wong, Cold Spring Harbor Laboratory Press, 2011.
14. Bhise, N, Gray, RS, Sunshine, J, Htet, S, Ewald, AJ, Green, JJ, "The relationship between terminal functionalization and molecular weight of a gene delivery polymer and transfection efficacy in mammary epithelial 2-D cultures and 3-D organotypic cultures". Biomaterials. 2010 Nov;31(31):8088-96.
15. Nakasone ES, Askautrud HA, Kees T, Park JH, Plaks V, Ewald AJ, Fein M, Rasch MG, Tan YX, Qiu J, Park J, Sinha P, Bissell MJ, Frengen E, Werb Z, Egeblad M, "Imaging tumor-stroma interactions during chemotherapy reveals contributions of the microenvironment to resistance", Cancer Cell. 2012 Apr 17;21(4):488-503.
16. Ewald AJ, Huebner RJ, Palsdottir H, Lee JK, Perez MJ, Jorgens DM, Tauscher AN, Cheung KJ, Werb Z, Auer M, "Mammary collective cell migration involves transient loss of epithelial features and individual cell migration within the epithelium", J Cell Sci. 2012 Jun 1;125(Pt 11):2638-54.
17. 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.
18. Nguyen-Ngoc KV and Ewald AJ, "Mammary epithelial elongation and myoepithelial migration are regulated by the composition of the extracellular matrix," J Microsc. 2013 Sep;251(3):212-23.
19. Beck JN, Singh A, Rothenberg AR, Elisseeff JH, Ewald AJ, "Coordinate regulation of epithelial dissemination by the mechanical and adhesive properties of the tumor microenvironment," Biomaterials, 2013 Dec;34(37):9486-95.
20. Nguyen-Ngoc KV, Shamir, ER, Huebner RJ, Beck JN, Cheung KJ, Ewald, AJ, "3D Culture Assays of Murine Mammary Branching Morphogenesis and Epithelial Invasion," Methods in Molecular Biology, 2014, In Press.
21. Cheung KJ, Werb Z, Ewald AJ, "Collective invasion in breast cancer requires a conserved basal epithelial program," In Press at Cell. Est. Pub. Jan 16, 2014.