gillespieProfessor of Surgery
Co-Director, UAB Brain Tumor SPORE
Leader, Brain Tumor Tissue and Brain Tumor Animal Models Core Facilities

Address: Tinsley-Harrison Building, room 1052
Birmingham, AL 35294
Telephone: (205) 975-0438






B.A. (Biology & Chemistry), University of Mississippi
M.Sc. (Cytogenetics),University of Mississippi
Ph.D. (Immunology & Immunogenetics), University of Mississippi, 1971
NCI Postdoctoral Fellow, University of Kansas Medical Center

Research Interests

The main thrust of my research is to develop and test specific therapies for treatment of malignant brain tumors in adults and children. One current focus is construction of replication conditional herpes simplex viruses that are both oncolytic for glioma cells and express foreign therapeutic genes. Gene transfer includes both pro-drug converting enzymes and cytokines under different promoter systems. Pro-drug enzyme systems currently being studied are cytosine deaminase (CD) alone or as a fusion protein with uracil phosphoribosyl transferase (UPRT) and purine nucleoside phosphorylase (PNP). A second focus involves studies cytokines expressed from replication competent HSV that include TNFa, IL-2, IL-4, IL-5, IL-10, IL12, IL-16. These systems are validated by in vitro assays first before being advanced to safety and efficacy assessment in a variety of murine models of intracranial malignant gliomas. These models include transplantable intracranial gliomas of human origin (in immunocompromised scid or nude mice) or mouse origin (in syngeneic conventional mice). We also have acquired 2 transgenic glioma mouse models and use high-field strength (8.5T) magnetic resonance imaging to detect and monitor tumor growth in transgenic mice. One intriguing observation is the fact that many of these viral oncolytic and transgene therapies are markedly enhanced by modest doses of whole brain irradiation. This phenomenon is being studied at the cellular and molecular levels to determine how it can be best employed as a therapeutic strategy. Vectors that are to be advanced to clinical trials are tested for neurotoxicity in non-human primates. Finally, small molecules that exert an anti-angiogenic effect on tumor neovasculature or that induce apoptosis in human glioma cells are being studied as therapeutic agents in vitro and in animal models of malignant brain tumors.