Brain tumors can be deadly, and the typical treatments — surgery, chemotherapy and radiation — carry significant risks. The Richardson lab, led by Angela M. Richardson, MD, PhD focuses on developing novel therapeutic strategies and preclinical models to enable improved translation from the laboratory to the clinic. Her group aims to improve preclinical modeling of brain tumors to more accurately mimic the environment within patients. Oxygen levels within the body and within tumors are significantly lower than oxygen levels within ambient air. One set of studies is aimed at understanding the effect of these different oxygen levels on brain tumorigenesis and chemoresistance. In related studies, the Richardson lab is exploring the use of viral vectors for suicide gene activating therapy to treat disseminated brain cancer (leptomeningeal disease) as well as solid tumors. This combination of studies aims to optimize delivery methods, mimic the treatment conditions of patients, and improve understanding of immune responses within the tumor microenvironment.
Active Research
Tumor selective retroviral replicating vectors for the treatment of leptomeningeal medulloblastoma
Retroviral replicating vectors infect tumor cells and can be armed with the capability to implant a gene selectively into cancer cells. This gene is then expressed and is able to convert a prodrug—typically benign when given systemically—into an active chemotherapy drug within the tumor cells. Medulloblastoma is the most common solid brain tumor in children. Richardson has shown that this viral vector is able to spread through, and kill, tumor cells. This specific project investigates the efficacy of this viral vector technology in the most lethal form of medulloblastoma, leptomeningeal disease—disseminated spread of cancer throughout the central nervous system.
Functional consequences of differing oxygen tensions on brain tumor
Cancer cells will be isolated from primary tumors under conditions of differing oxygen tension (from 1%, hypoxia, to 21%, normoxia = room air). Migration, invasiveness, and chemoresistance are being explored under these different conditions. The underlying cell signaling pathways are then interrogated to identify the cause of phenotypic differences.
Research Funding
Neurosurgical Education and Research Foundation, Young Clinical Investigators Grants
IU School of Medicine Department of Neurosurgery Start-up Funds
