The Johns Hopkins Engineering in Oncology Center (EOC) will explore the mechanical forces in cancer that bolster the tumor metastatic cascade. Metastatic disease causes the preponderance of deaths related to cancer. Relative survival significantly decreases for cancer patients who present with metastases at the time of their diagnosis. This center brings together experts in cancer biology, molecular and cellular biophysics, applied mathematics, materials science, and physics to study and model cellular mobility and the assorted biophysical forces involved in the metastatic process.
Our scientific approach is to perform an integrated analysis using biophysical, biochemical, biological, engineering, and computational approaches to gain insight into the cellular, molecular, and physical mechanisms underlying the functional interactions critical for establishing the intracellular and extracellular conditions favorable for metastasis. We are interested in the role of mechanical forces in cancer tumor growth and the metastatic cascade.
Director: Denis Wirtz, is a Professor of Chemical and Biomolecular Engineering and Materials Science in the Whiting School of Engineering and a member of the Oncology Department at the Johns Hopkins School of Medicine. He is an expert in cell and molecular biophysics and in the development of new methods grounded in physical principles, including statistical mechanics and polymer physics, to probe and establish the physical mechanisms of cell motility, intercellular adhesion, and microrheology. Wirtz serves as founding associate director of the Johns Hopkins Institute for NanoBioTechnology (INBT). He earned his Ph.D. in polymer physics at Stanford University.
Associate Director: Gregg L. Semenza, is the C. Michael Armstrong Professor at Johns Hopkins with appointments in Pediatrics, Medicine, Oncology, Radiation Oncology, Biological Chemistry, and the McKusick-Nathans Institute of Genetic Medicine. He serves as founding director of the Vascular Program in the Johns Hopkins Institute for Cell Engineering. He earned his M.D. and Ph.D. from the University of Pennsylvania; trained in pediatrics at Duke University; and was a post-doctoral fellow in Medical Genetics at the Johns Hopkins University School of Medicine.
Timothy C. Elston, Ph.D. (UNC) Sharon Gerecht, Ph.D. Kenneth W. Kinzler, Ph.D. Konstantinos Konstantopoulos, Ph.D. Greg D. Longmore, M.D., Ph.D (WUSTL) J. Michael McCaffery Martin L. Pomper, M.D., Ph.D. Aleksander S. Popel, Ph.D. Peter C. Searson, Ph.D. Sean X. Sun, Ph.D. Yiider Tseng, Ph.D. (UF) Charles W. Wolgemuth, Ph.D. (University of Connecticut) Kevin Yarema, Ph.D.
Project 1:
Interactions between HIF-1 and ECM
This project focuses on analyzing the makeup and physical properties of the extracellular matrix, the three-dimensional scaffold in which cells live. Normal cells live in a flexible scaffold, but cancer cells create a rigid scaffold that they climb through to invade normal tissue. This project will study how this change occurs and how it is affected by the amount of oxygen to which cancer cells are exposed. Previous studies have shown that cancer cells are deprived of oxygen, which incites them to more aggressively invade the surrounding normal tissues where oxygen is more plentiful. Hypoxia-inducible factor 1 controls the responses of cancer cells to low oxygen. Recently, drugs have been identified that block the action of HIF-1 and inhibit tumor growth in experimental cancer models.
Co-directors:Project 2: 3D
Cadherin-Mediated Adhesion in 3D
Cancer cells are able to modulate proteins on the surface almost like a protein brake that allows them to adhere or de-adhere in response to mechanical forces. This project will examine the physical basis for cancer cell adhesion and de-adhesion and how it increases the likelihood that cancer cells will break free, move into the bloodstream and migrate to other tissues.
Co-directors:Project 3:
Mechanochemical Effects on Metastasis
This project will investigate the effects of fluid mechanical forces at different oxygen tension microenvironments on tumor cell signaling, adhesion and migration. Fluid flow in and around tumor tissue modulates the mechanical microenvironment, including the forces acting on the cell surface and the tethering force on cell-substrate connections. Cells in the interior of a tumor mass experience a lower oxygen tension microenvironment and lower fluid velocities than those at the edges in proximity with a functional blood vessel, and are prompted to produce different biochemical signals. These differential responses affect tumor cell fateÑthat is, whether a cell will live or die, and whether it will be able to detach and migrate to secondary sites in the body.
Co-directors:Konstantinos Konstantopoulos, Ph.D. Martin L. Pomper, M.D., Ph.D.
Director: Denis Wirtz (wirtz@jhu.edu)
Administrative Manager: Sue Porterfield (sporterfield@jhu.edu)
Johns Hopkins Engineering in Oncology Center
214 Maryland Hall
3400 North Charles street
Baltimore, MD 21218
The Johns Hopkins Engineering in Oncology Center is administered by the Johns Hopkins Institute for NanoBioTechnology (http://inbt.jhu.edu)
For more contact information see http://inbt.jhu.edu/about/contact
