- Fax: 305-243-4955
- Associate Professor of Molecular and Cellular Pharmacology and Cell Biology
Dr. D'Urso's research interests include: cell cycle control of DNA replication, cell cycle checkpoints, and cell cycle control in stem and progenitor cells.
Uncontrolled cell proliferation is the hallmark of cancer. In rapidly growing tumors most therapeutic strategies involve treatment with chemotherapeutic agents that block cell division by either interfering with DNA replication or chromosome segregation. Dr. D'Urso's laboratory investigates the mechanisms that control DNA replication initiation in eukaryotic cells and studies the checkpoint controls that prevent mitosis in the absence of a complete round of
DNA synthesis or in response to DNA damage. Dr. D'Urso's lab uses fission yeast as a model system to investigate the underlying mechanisms of
these phenomena. They have found that a key protein in the assembly of the replication initiation complex is DNA polymerase epsilon (Pol e), whose C-terminal non-catalytic domain plays a critical role in early events of S phase. Their current model is that Pol e interacts with other components of the replication initiation complex and that these interactions are essential to allow efficient initiation of replication. Interestingly, while deletion of the
N-terminal half of Pol e had no effect on yeast cell viability, it activated a novel checkpoint to inhibit cell division. Checkpoint activation is also observed in other replication initiation defective mutants identified by their group, suggesting that this checkpoint responds specifically to blockade of the initiation of DNA replication. Their future goal is to fully characterize this checkpoint pathway, and to identify small molecule inhibitors that block initiation and trigger
the checkpoint control. Interestingly, cells defective in DNA replication initiation display a very low level of spontaneous mutations, suggesting that blocks
to initiation may be less mutagenic that those affecting DNA elongation. Since processes regulating DNA replication and repair are highly conserved in evolution, the D'Urso lab is investigating how these checkpoint controls may have relevance to human cells and to the responses of normal and malignant cells to chemotherapeutic agents and DNA damage. Moreover, their studies may lead to the identification of novel drug targets for cancer treatment and reveal potentially less mutagenic strategies to block cell cycle progression in cancer .
Imperial Cancer Research Fund
University of Washington
University of California
Gennaro D'Urso, Ph.D., joined University of Miami in 1997, following a cell cycle Postdoctoral Fellowship with Nobel laureate Paul Nurse at the Imperial Cancer Research Fund, UK. Dr. D'Urso is currently an Associate Professor in the Department Molecular and Cellular Pharmacology at University of Miami. He has contributed to graduate course development and teaching and led seminars for post-doc fellows.