AACR-QuadW Foundation Fellowship for Clinical/Translational Sarcoma Research
The AACR-QuadW Foundation Fellowship for Clinical/Translational Sarcoma Research represents a joint effort to encourage and support a postdoctoral or clinical research fellow to work on mentored sarcoma research and to establish a successful career path in this field. Funded research may be translational or clinical in nature.
Ewing sarcomas are driven by fusions of EWS and ETS transcription factors, most commonly EWS::FLI1. Cells with lower EWS::FLI1 activity have more metastatic phenotypes. Yet, the molecular mechanisms underlying this aggression are largely unknown. Dr. Wrenn has previously identified a subset of mesenchymal and extracellular matrix-associated genes which mark pro-metastatic, EWS::FLI1-low subpopulations. In this project, she aims to identify key upstream regulators of this cell state that can be targeted to reduce metastatic progression, and to determine if these EWS::FLI1-low subpopulations cooperatively promote metastasis of other adjacent cells through the secretion of paracrine and tumor microenvironment remodeling factors.
Dr. Wrenn received her PhD from the University of Washington’s Molecular & Cellular Biology Graduate Program. She conducted her dissertation research at the Fred Hutchinson Cancer Center, studying how cell-cell interactions promote metastasis in breast cancer. She is currently a postdoctoral fellow at the Ben Towne Center for Childhood Cancer Research at Seattle Children’s Hospital, where she focuses on the relationships between epigenetic plasticity, the tumor microenvironment, and metastasis in Ewing sarcoma.
Acknowledgement of Support
My goal is to develop an independent research program that tackles difficult unanswered questions in sarcoma biology, including identifying mechanisms of metastasis. The AACR-QuadW Foundation Sarcoma Research Fellowship in Memory of Willie Tichenor will provide exceptional support and training as I work to understand how metastatic cell subpopulations can be identified and therapeutically targeted.
Despite aggressive treatment of sarcomas and progress in understanding the genomic landscape of this disease, the five-year survival of patients with metastatic rhabdomyosarcoma (RMS) remains 30%. Understanding how RMS cells use nutrients to fuel growth in local vs. metastatic disease may provide unique opportunities to target RMS. Dr. Patel’s preliminary data suggests that radiation therapy induces sarcomas to preferentially utilize glutamine and that inhibition of glutamine metabolism can radiosensitize RMS. He aims to understand how glutamine deprivation radiosensitizes sarcomas and to determine the therapeutic potential of targeting central carbon metabolism in RMS.
Dr. Patel received his MS from the Illinois Institute of Technology and his PhD from Case Western Reserve University. His PhD dissertation project, funded by NASA, focused on the impact of space radiation on the hematopoietic system. As a postdoctoral associate at Duke University Dr. Patel studies metabolic vulnerabilities of rhabdomyosarcomas. His goal is to radiosensitize sarcomas through metabolic interventions and translate the findings into clinical trials for rhabdomyosarcomas patients.
Acknowledgment of Support
The 2021 AACR-QuadW Foundation Fellowship for Clinical/Translational Sarcoma Research provides necessary funding to pursue pharmacological inhibition of glutaminase as a therapeutic avenue for rhabdomyosarcoma patients in the future. The funding will also provide preliminary data for future grant applications and help with my training as I take a path towards becoming an independent investigator.
Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive soft tissue sarcoma, most commonly seen in adolescent and young adult males. DSRCT is defined by a single recurrent mutation, EWS-WT1, a dysregulated transcription factor, that alters the expression of more than 1500 genes. Dr. Gedminas’ previous work defined DSRCT cells as absolutely dependent on EWS-WT1 for survival. Dr. Gedminas’ current work will exploit this dependency as a therapeutic vulnerability using the small molecule lurbinectedin which she has shown to inhibit the expression of EWS-WT1. The goal of this study is to elucidate the mechanism of EWS-WT1 suppression by lurbinectedin to guide the administration of this compound and identify novel combination therapies.
Dr. Gedminas received her MD from the Chicago Medical School at Rosalind Franklin University of Medicine and Science, followed by residency training in pediatrics at Advocate Children’s Hospital. Following completion of her fellowship in pediatric hematology and oncology at Helen DeVos Children’s Hospital/Michigan State University, Dr. Gedminas received additional training as a pediatric solid tumor fellow at the Children’s Hospital of Philadelphia, where she now continues as an instructor and conducts sarcoma research.
Acknowledgement of Support
The AACR-QuadW Foundation Fellowship for Clinical/Translational Sarcoma Research provides me with essential support to continue my work developing novel therapeutic approaches for desmoplastic small round cell tumor while I continue the path toward becoming an independent investigator in the field of pediatric sarcoma.