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History of Our Laboratory
Research Areas
Our group began in 1977 with a research interest in the mechanisms of chromosomal DNA replication. We defined the biochemical functions of proteins in the human replication system. The proteins in this complex display unique mechanisms of protein-DNA interaction. Specifically, many of them associate with PCNA, a toroidal sliding clamp protein that facilitates movement and coordinated action of the other proteins. Some proteins in the complex have tracking mechanisms of their own. An example is the flap endonuclease that enters a DNA strand from the 5’ end and then moves to the point of cleavage.
Maintenance of genome stability is a top priority of human cells. This process slows aging and suppresses carcinogenesis. One mechanism is a signaling pathway that recognizes when chromosomal DNA has been damaged, and stops DNA replication to allow for DNA repair. A major repair pathway, base excision repair, employs mostly the same enzymes as the replication system. How does the cell disconnect these enzymes from replication and reassemble them for repair? Current work suggests that they are dissociated from the PCNA and reassembled around a repair nuclease and coordination protein called APE.
Another area of work in our laboratory is analysis of the steps of HIV DNA replication and recombination. The replication mechanisms of the virus differ from those of the host cell in many ways. We are particularly interested in understanding those differences, since they provide sites for therapeutic interference with viral replication by means that do not disrupt human cellular function.
We have also investigated the mechanism by which human steroid receptors regulate gene expression. This project has entered an engineering phase in which we can introduce structurally modified receptors into cells to regulate the expression specific genes. This technology is a novel approach to potential anti-tumor therapy.
We have published over 190 research papers on our work.
People
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Current Lab Members and Families |
Approximately 25 graduate or MD.-Ph.D. students and 25 postdoctoral fellows have trained in our laboratory and contributed to the advancement of our work. About half of these now have faculty positions at universities. The other half are employed as scientists or group leaders in the biotechnology or pharmaceutical industries. Several have pursued related careers such as patent law. Our area of research is popular in corporate settings since it is an excellent background for projects on DNA amplification and use of DNA in medical diagnostics.
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