Harvard Catalyst Profiles

Rhabdomyosarcoma (RMS) accounts for 50% of all soft-tissue childhood sarcomas and is characterized by tumor cells that molecularly and morphologically resemble undifferentiated skeletal muscle. Work from our group has recently identified a cancer stem cell in a subtype of RMS that drives therapy resistance (Wei et al., Nature Cancer 2022), yet mechanisms governing retention of the cancer stem cell state or pathways regulating therapy resistance within this subpopulation of cells are currently unknown. The goal for this project is to identify genetic modifiers that drive RMS growth, aggression, and stem cell self-renewal and to use this knowledge to uncover new therapeutic vulnerabilities to prevent tumor progression and relapse. Work will use loss-of-function and gain-of-function in human RMS cells to identify new cancer stem cell genes, 2) dynamically visualize effects on modulating human RMS CSC self-renewal, and 3) directly visualize the effects of therapy on RMS CSC self-renewal. This work will capitalize on the transgenic, photoconveratable cell lineage reporters that label and track human RMS CSCs.