Cancer: The wound that never heals

June 19, 2020

Funding from the Elsa U. Pardee Foundation will allow investigator to study muscle regeneration and cancer

By Alissa Kocer

Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children, accounting for up to 500 new cases in the US each year. It forms specifically in skeletal muscle tissue or hollow organs like the bladder and uterus and is hard to treat; survival rate for high-risk cases is only 30%.

Yarui Diao, Ph.D., assistant professor of cell biology, is trying to shed more light on this disease in an effort to come up with better treatment options. Diao received $191,000 through the Elsa U. Pardee Foundation to study the formation of tumors associated with RMS. 

Diao is using a genetically engineered mouse model (GEMM) of soft tissue sarcoma that was generated in Dr. David Kirsch’s lab. These mice are bred to develop RMS from muscle stem cell in response to tissue injury.

Through integrative analysis of publicly available CRISPR screening data on human RMS cells from the Broad Institute, as well as their in-house generated data from GEMM, Diao and team found a novel kinase in which to focus their investigations. This kinase is required for normal muscle repair but are instead hijacked by cancerous mutations that trigger RMS tumor formation.

Their goal is to determine the role and mechanism of this kinase and how it contributes to the formation of RMS tumors. Then they will test how well a small molecule inhibitor targets this kinase on RMS growth in both mouse models and in human RMS. In collaboration with Dr. Charlie Gersbach’s lab, Diao will also try to suppress those pro-tumor signals to get rid of the RMS via in vivo genome and epigenome editing.

“This work will help us improve our understanding of the molecular mechanism which is required for healthy tissue regeneration but induces RMS tumor transformation from adult stem cell when dysregulated.” Diao said. “It may also help provide new drug targets and candidate small molecule inhibitor for future treatment of RMS.”

In the long run, this research will help shed light on the development of an effective therapy for RMS treatment, which could make this cancer easier to treat.