Cell motility is a critical step in the metastatic cascade of events, as it enables cancerous cells dissociating from a primary tumor to navigate through interstitial tissues and ultimately colonize distant organs. Metastasizing cells migrate by remodeling their surrounding three-dimensional (3D) extracellular matrix to open up migratory paths, by following cancer-associated stroma cells that generate such paths, or by moving through pre-existing, 3D longitudinal channel-like tracks created by various anatomical structures. This seminar will present a multidisciplinary approach, integrating engineering principles and tools with molecular & cell biology techniques to understand cancer cell locomotion in precisely engineered microenvironments, which recapitulate the 3D longitudinal channels encountered in vivo. The plasticity of cancer cell migration will be discussed, focusing on how cells sense, adapt, and respond to different physical cues. Moreover, this presentation will outline how our current knowledge on the molecular mechanisms underlying cell motility has led to the development of a novel microchannel assay capable of distinguishing aggressive from non-aggressive cancer cells for accurate diagnosis, prognosis and precision care of cancer patients.
Konstantinos Konstantopoulos, William H. Schwarz Professor, Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, 21218
Joined the faculty of Chemical and Biomolecular Engineering at Johns Hopkins in 1997, and served as Department Chair from 2008 till 2017. He holds secondary appointments in the Departments of Biomedical Engineering and Oncology and is a core faculty member of the Institute for NanoBioTechnology at Johns Hopkins. He was elected Fellow of the American Institute for Medical and Biological Engineering in 2009 and of the Biomedical Engineering Society in 2012. He serves on the Editorial Board of numerous journals such as The American Journal of Physiology Cell Physiology, Technology, and Current Opinion in Chemical Engineering, and as Associate Editor of the Annals of Biomedical Engineering. His research is at the interface of engineering and biology pertinent to cancer metastasis. Some of his key bioengineering research contributions include the discovery of novel adhesion molecules (i.e., selectin ligands) involved in tumor cell adhesion in the vasculature, the biophysical characterization of these adhesive interactions at the single-molecule level, and the elucidation of novel signaling mechanisms during cell migration through physically confined microenvironments. He has published ~150 peer-reviewed articles in premier journals such as Cell, Nature Biomedical Engineering, Science Advances, Nature Reviews Cancer, Journal of Cell Biology, Blood etc. His work has been cited >9,400 times with an h-index of 55. Eleven of his mentees have launched successful academic careers in premier institutions such as Georgia Tech, University of Maryland College etc, whereas another seventeen have joined the government or industry and now hold leading appointments. He is currently the PI or MPI on four NIH R01 grants, including a Bioengineering Research Partnership grant, and a project PI on the renewed JHU Physical Sciences-Oncology Center.