The focus of our laboratory is to understand the molecular mechanisms governing malignant transformation in order to tailor novel therapeutic strategies. To effectively design novel biological drugs, a further understanding of the mechanism of cancer pathogenesis is required. Toward this end, we have carried out in the past 20 years studies to understand the crosstalk between those factors that contribute to cancer progression versus those that protect from it and to use them to our advantage to defeat cancer.
Gene therapy offers great potential for combating and curing a wide range of pathologic lesions. One of the major limiting factors in gene therapy has been the development of safe and effective delivery systems.
The emphasis of our research efforts is on imaging-guided drug delivery. The recent emergence of “molecular imaging” has set the stage for an evolutionary jump in diagnostic imaging and therapy. The ability to incorporate drugs or genes into detectable site-targeted nanosystems represents a new paradigm in therapeutics that will usher in an era of image-based drug delivery.
We have developed a novel gene therapy system based on the use of commercially available ultrasound contrast agents and adenoviruses that enhance the specificity of gene transfer in vitro as well in vivo. Ultrasound-mediated microbubble destruction improves the efficacy and reduces the non-specific expression of gene therapy vectors, providing a useful tool for manipulating gene expression in the living animal. We are currently working on further developing this useful targeting gene therapy tool to help close the gap that still exist between laboratory bench and bedside application.
Translational research (applied research aimed at closing the gap between the laboratory and the bedside) is the main focus of our studies. Recently in our laboratory, that is located within the Translational Genomic Research Institute at the Edwards Cancer Center, where the role of nutrition and cancer is an investigated topic, we have been focusing on the effects that various diet components have on the growth and survival of the root of cancer, i.e. the cancer stem-like cells.
We have developed a culturing method that enables the selection and proliferation of cancer stem-like cells (CSLCs) from patient tumor biopsies. We have also shown that primary cancer cell cultures generated in our lab from patient biopsies contain CSLCs, express stem cell markers, and are highly tumorigenic in nude mice. Based on our ability to establish primary cell culture from human cancer biopsies and to select and proliferate CSLCs from the same clinical tumor samples, we have set up a chemosensitivity drug assay, the ChemoID assay, which compares the sensitivity of CSLCs vs. bulk of tumor cells to chemotherapy. We are using this method to predict tailored chemotherapy strategies for lung, brain/spine, and breast cancer tumors in phase-I clinical trials.