The main focus of this laboratory is to develop and investigate the use of gene therapy tools, especially those specifically designed to disrupt oncogene expression, and then analyze their ability to sensitize or resensitize cancer cells to chemotherapy and/or radiation therapy.
The gene of most interest to this laboratory is Bcl-2 which produces a protein that is aberrantly expressed in many types of cancer cells and involved in preventing their death. We have designed a ribozyme (RNA enzyme) which effectively cleaves the RNA transcript of Bcl-2. The Bcl-2 ribozyme is delivered to the cells by an adenovirus vector.
We have shown a decrease in the Bcl-2 protein level as well as inhibition of cell growth and increase in the level of apoptotic cell death in many of the cancer cell types tested including oral cancer, glioblastoma, breast cancer and multiple myeloma. Additionally, the combination of Bcl-2 ribozyme and various chemotherapy drugs, (such as paclitaxel and etoposide) enhances the apoptotic effect in some of these cell lines as does gamma radiation combined with ribozyme treatment.