Mark Hatley Email & Phone Number

I am the Director of the Molecular Oncology Division of the Department of Oncology at St. Jude Children's Research Hospital. My laboratory explores the connection between pediatric cancer and normal development and cell fate decisions using rhabdomyosarcoma (RMS) as a model. We generate novel the genetically engineered mouse models to interrogate cells of origin of RMS using autochthonous in vivo systems that enable interrogation of how cell fate cooperates with genetic perturbations during tumor initiation. A cancer’s cell of origin is typically inferred from characteristics of the tumor cell. My work illustrated that this can be dangerous assumption. Through genetic fate mapping in a genetically engineered mouse model (GEMM) of embryonal fusion-negative RMS (FN-RMS) and alveolar PAX3::FOXO1 fusion-positive RMS (FP-RMS), I revealed that these tumors of presumed skeletal muscle origin can originate from an endothelial progenitor cells. This work identified cell reprogramming or developmental transdifferentiation as a mechanism of transformation in pediatric sarcoma and offers a potential explanation for the origin of FN- and FP-RMS that occurs in tissues devoid of skeletal muscle. My laboratory investigates how normal developmental processes are corrupted during transformation and establishes new RMS model systems to elucidate novel therapeutic vulnerabilities. My lab has recently reported that PAX3-FOXO1 driven fusion-positive RMS (FP-RMS) can develop from cell reprogramming of endothelial progenitors using GEMMs and human induced pluripotent stem cells (iPSC). Our new PAX3-FOXO1 driven iPSC model (iARMS), provides a system to dynamically interrogate the coupling of developmental cell state and PAX3-FOXO1 oncofusion function in a human model system. My laboratory is supported by a R01 grants from the NCI/NIH, the V Foundation for Cancer Research, the Rally Foundation for Childhood Cancer Research, and the American Lebanese Syrian Associated Charities.

Listed skills include Leadership, Cancer Research, Qpcr, Public Speaking, and 15 others.