Glioblastoma Tumor Microenvironment

Glioblastoma (GBM) is a highly aggressive type of cancer that originates in the brain and rarely metastasizes. The unique microenvironment of brain tumors is thought to be largely responsible for the characteristic aggressiveness and resistance to conventional treatments observed in GBM. However, the mechanisms underlying this relationship, are largely unknown. My lab works to develop physiologically translatable models that can be used to study how specific interactions between cells and the extracellular matrix in the microenvironment affect tumor physiology. We are engineering hydrogels as ex vivo culture systems based on hyaluronic acid (HA), a matrix polysaccharide abundant in the brain, to mimic the various aspects of the tumor microenvironment. HA and its cell surface receptors are dramatically upregulated near GBM tumors and this shift likely has a substantial contributes to the increased the migratory capacity and resistance to chemotherapeutic drugs. GBM cells cultured within these 3D environments more closely mirror their in vivo counterparts than those cultured using standard methodologies. Precise and independent control of the biochemical and biophysical landscape in these culture platforms enables investigation of the quantitative effects of these features on cell physiology so that clinically relevant data can be acquired in an ex vivo setting. Our research aims to characterize the microenvironment of clinical tumors and engineer culture planforms for patient-derived GBM cells that recapitulate these features. We then apply these cultures to better understand tumor physiology and develop new, patient-tailored treatment strategies.