- Post Doctoral
MIT Unit Affiliation:
- Biological Engineering
Date PhD Completed:
Top 3 Areas of Expertise:
Expected End Date of Post Doctoral Position:
For many cancers, dissemination of tumor cells to form metastases is not only a hallmark of the disease but an essential step to mortality. Migration and dissemination are complex, multistep processes, and study of their regulation has been challenging. Metastases need only be driven by a rare subpopulation of tumor cells, and a portion of dissemination is necessarily interaction with the cell's environment and thus cell extrinsic. Experimentally, there is additional uncertainty as exactly how to best assess migration outside of the complex in vivo environment. To develop a systems perspective of invasive disease, we first examine some of the experimental models used to study cell migration. We then apply this knowledge to examine regulation by proteases of endometrial cell invasion, and the pro-migratory effects of receptor crosstalk in breast carcinoma cells. Finally, extending from clear limitations in our knowledge of signaling regulation specifically within the invasive subpopulation of cells, we develop a model of ligand-mediated signaling for a receptor often expressed specifically during the process of dissemination. In total, this thesis extends systems biology techniques to the study of cell migration within the extracellular environment, with focus on that subpopulation of cells most directly implicated in the formation of metastatic disease.
Top 5 Awards and honors (name of award, date received):
5 Recent Papers:
Meyer*, A.S., A.J.M. Zweemer, D.A. Lauffenburger*. “The AXL receptor is a sensor of ligand spatial heterogeneity.” Cell Systems (2015).
Meyer, A.S., M.A. Miller, F.B. Gertler, D.A. Lauffenburger. “The receptor AXL diversifies EGFR signaling and limits the response to EGFR-targeted inhibitors in triple-negative breast cancer cells.” Science Signaling (2013).
Miller*, M.A., A.S. Meyer*, M. Beste, Z. Lasisi, S. Reddy, K. Jeng, C.-H. Chen, J. Han, K. Isaacson, L.G. Griffith, D.A. Lauffenburger. “ADAM-10 and -17 regulate endometriotic cell migration via concerted ligand and receptor shedding feedback on kinase signaling.” Proc. Natl. Acad. Sci. U.S.A. (2013).
Meyer, A.S., S.K. Hughes-Alford, J.E. Kay, A. Castillo, A. Wells, F.B. Gertler, D.A. Lauffenburger. “2D protrusion but not motility predicts growth factor-induced cancer cell migration in 3D collagen.” J. Cell Biol. (2012).
Miller, M.A., M. Moss, G. Powell, R. Petrovich, L. Edwards, A.S. Meyer, L.G. Griffith, D.A. Lauffenburger. “Tar- geting autocrine HB-EGF signaling with specific ADAM12 inhibition using recombinant ADAM12 prodomain.” Scientific Reports (2015).