David Cortez, PhD
Ingram Professor of Cancer Research
Professor of Biochemistry
Vanderbilt University School of Medicine
2013-2014 BCRF Project:
(The RGS Labs International Award)
Triple negative breast cancer (TNBC) comprises approximately 25 percent of breast cancer deaths. There is currently no proven targeted therapy for this disease subtype; thus, there is a critical need to develop better therapeutic options. Dr. Cortez hypothesizes that at least a subset of these cancers are especially dependent on DNA repair mechanisms that are coordinated by the ATR checkpoint kinase signaling pathway. He is working to develop small molecule inhibitors of the ATR pathway in collaboration with other researchers at the Vanderbilt-Ingram Cancer Center. Dr. Cortez has concentrated on two targets, ATR and RPA, since they are essential nodes in the pathway. His studies of an ATR selective inhibitor indicate that it kills cells due to a requirement for ATR signaling to complete DNA replication. ATR inhibition is synergistic with other chemotherapeutic agents such as platinum crosslinking drugs. Screening approaches have also identified small molecule inhibitors that are being optimized. Finally, Dr. Cortez completed a synthetic lethal screen to identify cancer contexts where anti-ATR pathway drugs would be particularly useful. This screen indicates that BRCA mutations do not sensitize to ATR inhibitors, but loss of function of several other genes including ATM, ERCC1, and RNR do cause hypersensitivity. Dr. Cortez is also investigating the mechanism by which changes in other DNA damage response protein expression alter the cellular effects of ATR inhibitors. These studies will help direct clinical trials of ATR pathway inhibitors.
Dr. Cortez graduated summa cum laude from the University of Illinois at Champaign-Urbana with Highest Honors in Biology and Biochemistry. He received his doctorate in 1997 in Molecular Cancer Biology from Duke University. After post-doctoral training as a Jane Coffin Childs Fellow at the Baylor College of Medicine, Dr. Cortez joined the Vanderbilt faculty in 2002. He was promoted to Associate Professor in 2007 and Professor of Biochemistry and Ingram Professor of Cancer Research in 2009. Dr. Cortez is Director of Graduate Studies in the Department of Biochemistry, and a member of the Editorial Boards of the journals Cell Reports, Molecular and Cellular Biology, and Journal of Biochemistry. He became co-leader of the Genome Maintenance Program in the Vanderbilt-Ingram Cancer Center upon its inception in 2007.
Dr. Cortez’s research focuses on the mechanisms that maintain genome integrity. His research has been published in journals including Science, Genes and Development, Cell Reports, Molecular and Cellular Biology, Journal of Biological Chemistry, Proceedings of the National Academy of Sciences, Cancer Research, and Molecular Cell. He has received several awards recognizing his scientific achievements including the Howard Temin Award from the National Cancer Institute, the Wilson S. Stone Memorial Award, and a Pew Scholar Award from the Pew Charitable Trusts.