(Blacksburg, June 18, 1998) -- Johnson & 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 multicellular 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," explained 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 explains. 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 anticancer drugs inhibit cell division by interfering with either DNA synthesis or repair, RPA is a potential target for therapeutic intervention.
"Using deletion analysis and site-directed mutagenesis we have identified promoter elements that regulate the glycogen phosphorylase gene during cell differentiation of Dictyostelium," Rutherford reports.
The group also discovered that RPA has a dual role in DNA repair and cell differentiation: it is a key protein in recognizing and repairing UV-damaged DNA, helping to prevent one form of skin cancer (xeroderma pigmentosum), and it interacts with the tumor suppresser gene, p53. "Additional supporting evidence from the model system is needed before a parallel study can be taken in the human cancers," he explains.
"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 underway 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 says.
"The proposed project will define an experimental system in which these molecular interactions can be tested, and thus provide a foundation for efforts to control differentiation and proliferation in a therapeutic context," he says. "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.
"Replication Protein A (RPA), may be representative of the molecular components of the genetic switch from proliferation to differentiation," says Rutherford. "By studying Replication Protein A and exploiting its capacity as a molecular 'hook' to expand our knowledge of the network of interactions required for differentiation, we hope to uncover the details of one of the unifying principles of differentiation: the molecular framework underlying a cell's decision to depart from the cell cycle and to enter into a program of differentiation."
The check for the continued research was presented by Connors and Susan Greger and David Atkins, corporate directors of the Corporate Office of Science and Technology at Johnson & Johnson, at a program at the Fralin Biotechnology Center at Virginia Tech on Thursday, June 18. Greger said that Johnson & Johnson has given about 100 "focused giving grants" in the last 10 years to support basic research.
Contact for further information:
Dr. Charles L. Rutherford, Professor of Molecular and Cellular Biology
Virginia Tech
Blacksburg, VA 24061
Phone: 540-231 - 5349; fax: 540-231 9307;
email; rutherfo@vt.edu
http://www.biol.vt.edu/department/rutherford.html
Dr. Richard W. Connors
Janssen Research Foundation
(215) 628-5651 or rconnors@prius.jnj.com
Susan Greger
Johnson & Johnson
(732) 524-2553 or sgreger@corus.jnj.com