Gilbert Rahme is a PhD candidate in Dr. Mark Israel’s lab in the Department of Genetics working on defining critical genes that control pathogenesis of Glioblastoma (GBM), the most aggressive primary brain tumor.
“GBM is a devastating disease that leads to death in most patients 12 to 15 months post-diagnosis. Current methods of therapy which include surgery, radiation therapy, and temozolomide chemotherapy only marginally improve survival. This aggressive profile for GBM is at least partially mediated by the ability of tumor cells to disseminate and spread throughout the brain which makes it very hard for full surgical resection. Additionally, with the brain being a central organ for dictating several physiological processes throughout the body, GBM tumor cell dissemination poses a huge risk for the survival of a patient because it can compromise the physiology of the entire body. One major way GBM cells disseminate, or invade, is through the expression and secretion of Matrix Metalloproteinase 2 (MMP2). You can think of MMP2 as a “pac-man”-like protein that is produced and secreted by cancer cells to degrade the “wall” of protein found in every organ paving the way for cancer cells to invade a certain organ. Although the importance of MMP2 is clear, the mechanisms that regulate its production in GBM are not fully elucidated.
We have discovered that the protein product of a gene called ID4 inhibits tumor cell invasion and found that this function is exerted through an inhibitory effect of ID4 on the production of MMP2. These results were obtained using GBM-derived cancer cells from human patients. Through funds obtained from the graduate alumni award, we were able to analyze primary tumor specimens collected from human GBM patients and show that ID4 expression can predict survival of GBM patients. GBM patients with high ID4 expression in their tumors survive longer than patients with low ID4 expression in their tumors. This finding is directly consistent with our previous results and our hypothesis that ID4 can suppress tumor invasion leading to less aggressive tumors. We are now using this information to assess whether ID4 has other functions in GBM that lead to less aggressive tumors.”