The research activities of my laboratory focused on the following two areas: cancer gene therapy and radiation induced genetic instability.

In the area of cancer gene therapy, our research is focused on three projects. The first one is to develop a novel, inducible gene therapy approach that utilizes hyperthermia to control gene expression. This research is carried in collaboration with Dr. Mark W. Dewhirst, who is the Director of the Duke Hyperthermia Cancer Treatment Program. We have shown that it is possible to to used this approach to deliver sufficiently high levels of theraputic genes, such as those encoding cytokines, in to tumors with minimal normal tissue toxicity. The second project is to develop gene therapy approaches that can enhance cancer radiotherapy. Toward this goal we have developed adenovirus and adeno-associated virus vectors that encode potent immunostimulatory cytokines or anti-angiogenic proteins that target tumor vasculature. We have shown that some of the gene therapy vectors can synergistically enhance the therapeutic effects of radiation in murine tumor models. The third project is to develop better viral vectors for cancer gene therapy. A recent example is the development of more efficient, scaled-up approach for the production of adeno-associated virus vectors. Progress in this area is expected to facilitate the application of this promising vector on a wider scale.

In the area of genetic instability, we are studying the phenomenon of radiation induced genetic instability. In particular, the persistent genetic instability displayed by mammalian cells after surviving a sublethal radiation dose. The results could have serious implications in both radiation treatment and radiation induced secondary carcinogenesis.

Finally, we have two collaborative research projects. The first one is to study early events in tumor angiogenesis, especially its relationship with host tissue and hypoxia. Efforts are directed at the genetic levels by use of such techniques such as the tumor window chamber, live fluorescence labeling, and cDNA microarrays. This project is being carried out in collaboration with Dr. Mark Dewhirst’s Tumor Microcirculation Laboratory. The second is to study and develop novel gene delivery approaches and explore their applications in cancer gene therapy. This is done in collaboration with the laboratory of Dr. Fan Yuan, a faculty member at Department of Biomedical Engineering.