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.
Rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma of childhood, is comprised of two major subtypes: fusion-positive RMS containing PAX3/7-FOXO1 translocations and fusion-negative RMS characterized by RAS pathway activation. Survival rates of patients with refractory or relapsed disease drop to < 20%, with little improvement seen in treatment options in the past four decades. Cancer stem cells, drivers of relapsed/refractory cancers, have been recently identified in fusion-negative RMS. Dr. Eng aims to characterize the mechanisms by which specific transcription factors regulate human fusion-negative RMS growth and cancer stem cell function. This may lead to novel therapeutic targets to prevent relapse in RMS patients.
Dr. Eng completed her doctoral degree in the Department of Molecular Medicine and Pathology at the University of Auckland, New Zealand. Her work was focused on elucidating the developmental origins of lymphatic vessels, understanding the mechanisms regulating lymphangiogenesis, and developing novel antilymphangiogenic therapies to prevent lymphatic spread of tumor cells. She is currently continuing her training in cancer biology as a postdoctoral fellow at Massachusetts General Hospital.
Acknowledgement of Support
“My goal is to become an independent pediatric cancer biologist who specializes in uncovering novel therapeutic targets for curing children with sarcoma. The support gained from this fellowship is an important and invaluable contribution to my ongoing development as a researcher and assists with my transition into an independent investigator.”
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 doctoral degree 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.