Corrado Santocanale is Professor of Molecular Medicine at NUI Galway and member of the Center for Chromosome Biology since 2007. He received his Ph.D. in Cellular and Molecular Biology from the University of Milan, Italy.

As postdoctoral fellow at the Imperial Cancer Research Fund (now Cancer Research UK) in John Diffley’s laboratory, he studied the mechanisms that control the initiation of DNA replication uncovering the “origin firing checkpoint”, a pathway that prevents the activation of late firing origins in response to the inhibition of replication elongation or DNA damage.

In 1999 joined Pharmacia Upjohn (subsequently Pharmacia Corp. Pfizer and Nerviano Medical Sciences) leading a preclinical drug discovery program aimed at discovering and developing CDC7 protein kinase inhibitors as anti-cancer therapeutics. His lab at NUI Galway is interested in studying the mechanisms of DNA replication in human cells and exploiting the results in this field for therapeutic purposes.

ABSTRACT

Title: Blocking DNA replication before it starts: insights into CDC7 targeting drugs using functional genomics approaches

Summary: The CDC7 kinase is a key switch for the initiation of DNA synthesis from replication origins.

Many institutions are developing CDC7 inhibitors (CDC7i) as potential agents to treat refractory p53 deficient cancers. CDC7i have excellent antitumor activity, however this varies greatly among cell lines and tumor types, indicating that the genetic background of the cell strongly influences the outcome.

I will discuss the mechanism of action of CDC7 inhibitors and our recent efforts to identify the genes that modulate the cellular responses to CDC7i by developing and performing genome wide loss-of function screens using CRISPR/Cas9 technology.

I will also present evidence suggesting that CDC7 kinase has a novel function at replication forks, which can drive replication-dependent genome instability.