My laboratory is interested in how the human genome is replicated. Every time one of our cells divides, billions of base-pairs must be duplicated in the correct sequence and in coordination with other important processes in the nucleus such as gene expression and DNA repair. To ensure that the genome is completely and accurately duplicated during every round of cell division, our cells use complex regulatory systems that determine when and where different parts of the genome are copied. We are just beginning to understand the mechanisms of this “replication program,” but we already know that deregulation of DNA replication leads to cancer and birth defects. We expect that defining the general principles and specific mechanisms of DNA replication control will ultimately lead to better treatments for a number of different diseases, including cancer.

To obtain both mechanistic and in vivo information, we study DNA replication using cultured human cells and zebrafish embryos. Because the zebrafish embryo develops externally, it provides an outstanding opportunity to understand how the genome is properly replicated during the multitude of cell divisions that must occur during embryogenesis. We are currently studying how DNA replication adapts to the vast array of cellular changes that occur during embryonic development. We are also delineating the basic mechanisms of DNA replication control. We are studying a number of recently discovered DNA replication control genes that are found in all vertebrates, including fish and humans. We are particularly focused on a DNA replication control gene called TICRR, which we discovered through a genetic screen in zebrafish. This gene is a pivotal component of the system that determines when and where DNA replication initiates throughout the genome.