The main research objectives of our laboratory are to study and develop novel therapies for the treatment of brain tumors as well as studying the molecular and cellular characteristics of these tumors. Specifically, we are studying treatments for a group of tumors known as malignant gliomas. Much of our laboratory work is focused on the development of herpes simplex virus type I based vectors for treatment of gliomas. These vectors are conditionally replicating and destroy the tumors through oncolysis. Additionally, they can be used as gene therapy vehicles to add an additional tumoricidal affect. We have constructed genetically-engineered herpes simplex viruses that express a wide variety of cytokines and chemokines as well as cell surface antigens, suicide genes, and anti-angiogenic compounds as well as other proteins with antitumor effects. After construction, these viruses are tested in a variety of in vitro and in vivo models. Ultimately, we plan to take these anti-tumor viruses into clinical trials for the treatment of malignant tumors. One such virus, G207, has been studied at UAB in previous trials; a new trial in conjunction with radiation will begin soon. A second virus, M032, was created in our lab and expresses IL-12. M032 has received approval for clinical testing and has entered clinical trials. We are also developing other methods of increasing the efficacies of these viruses to increase their oncolytic efficacy, spread and persistence in tumor tissue. With the success of these agents in glioma, our area of interest has expanded to include other neoplasms, such as breast, pancreatic, colon, and melanoma.