Patient Outcome Projects:
1) We have identified a gene mutation that affects patient outcome. This mutation does not appear to increase the risk of cancer but negatively impacts the treatment response. These studies began in a cell culture model where we showed cells with this mutation are resistant to treatments and have been translated to human studies.
2) We have a program to assess the role of depression in outcome of brain tumor patients. There is compelling evidence that depression will decrease immune system functioning. There is suggestive evidence that the immune system has been somehow compromised in cancer patients which has allowed the cancer cells to grow. Thus, we are combining the two areas of research to determine if brain cancer patients who are treated for depression have a better outcome than those whose depression is not treated. We will monitor the immune system in both treated and untreated patients to test our hypothesis that the depression has compromised the ability of the immune system to assist in attacking the cancer.
Translational Research Projects:
1) We have a nanotechnology platform that takes advantage of the unique expression of the receptor for a protein known as interleukin-13 (IL-13) on astrocytomas, the most aggressive form of brain tumor. We can target nanovesicles carrying anti-cancer drugs or genes that kill the cancer cells without harming normal tissue. We are also using the targeted nanovesicles to deliver contrast agents selectively to the tumor cells. This latter approach will enhance the tumor visibility, enabling the surgeon to more accurately assess the extent of the tumor. In addition, because of the unique expression of the IL-13 receptor on certain types of brain tumors, we hope to use the targeted delivery system to aide in the diagnosis of tumors. This project was selected by the National Cancer Institute to form a collaboration that will enable us to reach clinical trials faster. We have passed the initial characterization step with the nanovesicles and now are completing toxicology assays. We already have dramatic data showing our system is successful in destroying brain tumors in mice. Consequently, we are hopeful that we can begin Phase 1 clinical trials sometime this year.
We have recently learned that neurofibromatomas, a devastating peripheral nerve tumor, also express the receptor for IL-13 and have started studies to demonstrate the efficacy of our system in treating this form of cancer.
We have adapted our nanotechnology platform to carry genes or modified genes that can be targeted to the tumors. We have just started the in vivo efficacy studies, and the results are very promising.
2) We mentioned above the discovery in our laboratory that a certain mutation renders cancer cells resistant to treatment. We used these cells to screen for new drugs that may be effective anti-cancer agents and we found some. Importantly, the ones we found were all from the same drug family. We have developed a line of the new drugs that shows great promise in the in vivo studies.
Synaptic Signaling and Affective Disorders:
The Department of Neurosurgery has established a research program to monitor precisely the electrical and chemical activity of the mammalian brain at both single cell and neural network levels. By recording how the electrical signaling of neurons regulates dopamine and serotonin neurotransmitter activity in the midbrain, we are investigating the pathological mechanisms underlying depression, anxiety, and drug addiction. This program is further aimed at developing therapeutic interventions by manipulating and adjusting the electrical activity of the neural circuitry involved in the disorders.