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Screening for New Rhabdomyosaroma Pathogenesis Genes in a Drosophila Model

University of Texas Southwestern Medical Center
Kathleen Galindo
Grant Type: 
Young Investigator Grants
Year Awarded: 
Type of Childhood Cancer: 
Project Description: 

The Galindo lab's research is built upon a fundamental interest in the mechanisms responsible for childhood cancer. The lab focuses on tumors that grow from the soft tissues (e.g., muscle, fat), called sarcomas, which are notoriously aggressive, and prefer childhood tissues. Little is understood about sarcoma biology, explaining why they have been difficult to study, and cure. We investigate the most common soft tissue sarcoma, the muscle-type tumor rhabdomyosarcoma (RMS). The most deadly form of RMS is caused by abnormal fusion of two genes, PAX and FKHR, into one composite gene, PAX-FKHR. PAX-FKHR is tumor-inducing, converting otherwise normal muscle-type tissue into cancer cells, though how this process occurs is not understood. To dissect PAX-FKHR activity, the lab has engineered the laboratory fruit fly to express and react to human PAX-FKHR in critical and revealing ways. Of note about the fruit fly as a disease model system: 1) For virtually every important human gene, including cancer genes, a similar gene exists in the fly; & 2) While having similar biology, the fruit fly is comparatively 'simple', allowing for easier experimental manipulation and interpretation.  With the PAX-FKHR fly model, we have identified numerous new RMS genes; importantly, these genes are now avenues for novel treatments. We are successfully adapting these findings to RMS tissue and cell culture systems. With these insights, we aim to uncover the genetic underpinnings of RMS and devise new drug therapies, which will significantly improve our future ability to cure these deadly tumors.