By Susan Trulove
Spectrum Volume 20 Issue 34 - July 2, 1998
Johnson and Johnson Corp. and the Janssen Research Foundation have awarded a team of Virginia Tech biologists an $84,000 grant to pursue new discoveries regarding the chemistry that initiates cell differentiation, the point in the development of a multi-cellular organism at which cells become specialized for particular functions.
Results of the research by biology professor Charles Rutherford, Reyna Favis, research assistant professor, and Ian McCaffery, research associate, has the potential to become the backbone of gene therapy for cancer. "Dr. Rutherford's research is on the brink of a very interesting discovery in cancer biology, to identify critical points in signal transduction where there is the possibility for therapeutic intervention," said Richard Connors, principal scientist for oncology and endocrinology research with the Janssen Research Foundation.
Cancer cells multiply faster than normal cells, and continue to multiply, or proliferate. Whereas normal cells receive molecular information that stops cell proliferation and starts cell differentiation, in the cancer cell the signals are either not present or not received.
Those molecules that are involved in the transition point between proliferation and cell differentiation are of particular interest with respect to the formation of a cancer cell, Rutherford said. By using Dictyostelium, a type of slime mold widely used as a model system in the study of cell differentiation because of its similarity to human cell function at this level, Rutherford's research group discovered that a protein called Replication Protein A (RPA) acts not only in cell proliferation, but also is a regulator of cell differentiation. Because most anti-cancer drugs inhibit cell division by interfering with either DNA synthesis or repair, RPA is a potential target for therapeutic intervention.
"Additional supporting evidence from the model system is needed before a parallel study can be taken in the human cancers," he said. "Understanding the signaling pathways and molecular processes that lead to the genetic transitions between cell proliferation and cell differentiation is fundamental to devising therapeutic interventions for human cancer.
Gene therapy of cancer remains a potentially valid approach, and, in fact, clinical trials are under way in some cases. To be effective however, a valid gene therapeutic treatment must be based on the known molecular interactions that occur in the cell in response to cancer causing agents. Only after these molecular events are known, can the genes that are defective in the patient be targeted," Rutherford said.
"The proposed project will define an experimental system in which molecular interactions can be tested, and thus provide a foundation for efforts to control differentiation and proliferation in a therapeutic context," he said. "In this research we will test the hypothesis that replication-protein A functions as a DNA-replication factor during proliferative cell cycling and as a transcription factor during cellular differentiation."
The check for the continued research was presented at a program at the Fralin Biotechnology Center at Virginia Tech in June.