"Glioblastoma is a fatal disease that is recalcitrant to therapy. The Sontag Award will allow us to translate the new genetic understanding of this terrible disease into daring approaches to therapy that could one day save the lives of brain cancer patients."

- Dr. Clodagh O'Shea

Academic Appointments

  • Associate Professor, Molecular and Cell Biology Laboratory, William Scandling Developmental Chair, Salk Institute

About DSA-Funded Research

There is a desperate need to identify effective new therapies for the treatment of patients suffering from brain cancer. The p53 and Rb tumor suppressors are inactivated in almost all cases of human glioblastoma. Despite this, there are no approved rational targeted therapies to treat p53 and Rb mutant tumors. Our goal is to develop viruses that act as p53/Rb-tumor mutation guided missiles, specifically replicating within mutant brain tumor cells and bursting them open to release thousands of viral progeny that have the potential to seek out remaining tumor stem cells and distant micro-metastases. We will test the tumor selectivity of these viruses in powerful new mouse models of glioblastoma that faithfully recapitulate the human disease. Normally, human adenoviruses don’t replicate in mouse cells, which has severely hampered their preclinical evaluation. To overcome this limitation, we will create mouse adenovirus doppelgangers of the human therapeutic viruses, which have the potential to transform the clinical development and use of adenoviral therapies for brain tumors and other cancers. Unfortunately, many glioblastoma patients’ tumors are inoperable and it is difficult to deliver drugs across the torturous brain tumor blood vessels that proliferate abnormally to feed the tumor and distant metastases. Therefore, we will also exploit viruses that naturally infect blood vessels in the brain to develop new therapeutic agents that specifically ablate aberrant brain tumor blood vessels, starving the tumor to death. This would be a major breakthrough for cancer therapy.

Accolades

"Clodagh is simply one of the most talented and creative individuals that I have trained. She is a brilliant experimentalist and is extraordinarily intelligent."

Frank McCormick, Ph.D., F.R.S.
University of California, San Francisco

"Clodagh works objectively, amazingly hard, with awesome focus and great persistence, showing an uncanny knack and intuition for how things work and how experiments can be made to work. Impressive, too, is her contagious excitement, passion and urgency that she instills in all those who work with her."

Gerard Evan, Ph.D., F.R.S.
University of California, San Francisco

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