Samuel W. Brady Lab

The overarching objective within the Brady Lab is to use cancer genomics and pharmacology to identify improved pediatric cancer treatment approaches. Patients with cancer will often respond to their initial treatment, but sometimes, a small subset of cancer cells evade treatment and develop drug resistance; our lab aims to understand why and how that occurs. One method the team employs is identifying mutational signatures; prior research indicates that the sources of DNA mutations leading to acquired drug resistance within cancer cells can be identified using mutational signature analysis. For example, neuroblastoma has a mutational signature indicative of reactive oxygen species (ROS) DNA damage. These mutations may lead to drug resistance while conferring vulnerabilities to other therapies; discerning how to prevent or exploit these mutations is the next step toward developing better therapies and preventing relapses.

The team also uses mutational signatures to understand how existing therapies may induce secondary cancers in survivors later in life. Many pediatric cancer survivors will undergo treatment and be cured of their initial cancer but then develop a second cancer due to their prior therapy. Our lab uses mutational signatures and other genomic techniques to understand how therapy can induce specific mutations that initiate second cancers. The results of this work could help inform which therapies should be reduced to a lower dosage and which should be avoided entirely in certain patient populations.

Finally, we aim to tackle new therapeutic targets. Many existing cancer therapies are toxic, which is a significant problem for pediatric patients because their bodies are still developing. In order to develop treatments that will have the maximum impact on cancer cells with minimal impact on healthy tissue, the team is working to identify the genes that are unnecessary for human survival but vital to a cancer cell’s survival. This research will allow new therapies to target specific proteins and minimize treatment toxicity.