Our Science – McMahon Website
James B. McMahon, Ph.D.
The development and validation of cell-based assays for the discovery of potent reagents which selectively target cancer cells have been long-term goals of our Program. Since the early 1980's, continuing advances in cell culture techniques have allowed for remarkable breakthroughs in cancer cell biology. Early in vitro studies involving neoplastic transformation of rodent cells have provided valuable insights into the carcinogenic process. The ability to propagate both normal and malignant cells from a variety of experimental animal species set the stage for the necessary refinements of technologies to allow for the maintenance of human cells and tissues in vitro. Our laboratory has been at the forefront of the establishment and characterization of human tumor cell lines and their normal cell counterparts for use in bioassays. With the establishment of the NCI 60-cell panel and the creation of the Compare analysis program, many new classes of anticancer compounds were discovered. As was the case with many of the early cell-based screens, designed to screen for cytotoxic agents, most of the compounds were of limited clinical potential. The new era of genomics and proteomics along with advances in automation technologies are now providing insights into the molecular pathogenesis of cancer. These technologies will provide unprecedented opportunities for discovery and development of novel, molecularly-targeted agents for cancer.
Our primary goal is to use this ever-increasing knowledge base to develop and characterize novel cell bioassays which will target specific molecular targets and/or pathways. New in vitro assay formats and endpoints will be utilized to serve as platforms for examining the effects of test compounds on cells engineered with reporters linked to specific molecular targets. It is hoped that establishment of cellular assays based on this approach will quickly lead to the discovery of new, effective anticancer compounds with unique mechanism of action.
Though the main emphasis of research in the MTDP is aimed toward reducing the human cost of cancer, the program proactively interacts with collaborators to address other health-related concerns of high priority to the DHHS. One example of this type of interaction is the current collaboration between the MTDP and USAMRIID to test antiviral compounds, previously discovered in the MTDP, against a variety of emerging threats including the ebola virus and the virus responsible for sudden acute respiratory syndrome (SARS). In addition, MTDP's previous discoveries of potent anti-viral natural product peptides has resulted in the establishment of a worldwide network of collaborators who are employing the peptides for the microbiocidal protection from HIV. Through the responsible development of such collaborations, the MTDP extends the products of its screening and isolation efforts into areas of significant national and international need.
This page was last updated on 2/21/2013.