Some on-going projects
1) ECM molecules as signals for motility
In this project we are focused on the interactions and mechanisms of proteoglycans (brevican, versican) that inhibit the motility of normal neural cells but surprisingly stimulate the migration of glioma cells. We are also developing novel reagents to inhibit the signaling initiated by these proteoglycans and target them in the ECM of gliomas.
Glioma cells expressing brevican accumulate pro-adhesive fibrils of fibronectin (green) on the cell surface (magnif. 400x). Image from Hu
et. al., J. Biol. Chemistry (2008)
2) Novel targets in the ECM of gliomas
This project is focused on a novel glycoprotein named fibulin-3 that we have found in the ECM of gliomas but
absent from normal brain. We are studying how fibulin-3 enhances glioma cell migration and developing anti-invasive strategies against this molecule.
Tumor cells expressing fibulin-3 (green) invade diffusely in the brain parenchyma (magnif. 100x, © Viapiano Lab)
3) The small links in the ECM scaffold
We are also studying the expression of the HAPLN family, a group of small glycoproteins that link proteoglycans and
hyaluronic acid in the neural ECM scaffold, but are absent in the ECM of gliomas.
A model of link protein-hyaluronan-proteoglycan interaction, based in association studies
of the proteins HAPLN1 and aggrecan (© Viapiano Lab)
4) ECM topography and cell migration
This is a multidisciplinary collaboration with our colleagues Sean Lawler (Dept. Neurosurgery, OSU) and John Lannutti (Dept. Materials Science, OSU). Together, we are trying to reproduce the nanoscale structure of the neural ECM and the effects of substrate topography on the migration of glia and glioma cells.
A glioma cell migrating on a scaffold formed by aligned polymer fibers. Electron microscopy image courtesy of Lannutti Lab (OSU), from:
Johnson, Nowicki et. al. Tissue Eng (2009).
5) Manipulation of the tumor microenvironment
This is a collaboration led by Dr. Balveen Kaur (Dept. Neurosurgery, OSU) to study ECM-disruption strategies that can improve therapeutic efficacy
against malignant brain tumors.
A molecular model of an oncolytic Herpes Simplex virus (image from Russel Kightley Media), engineered by the Chiocca and Kaur Labs at OSU to specifically kill tumor cells.
|
