Ora Schueler-Furman, PhD
Project Title
A new approach for targeting Ewing’s Sarcoma
About the Investigator
Prof. Schueler-Furman is a leading expert in computational structural biology and protein interaction modeling. She earned her academic degrees from the Hebrew University and completed postdoctoral training with David Baker at the University of Washington. She is currently a Professor at the Institute for Medical Research Israel-Canada, in the Faculty of Medicine at the Hebrew University. Her research focuses on understanding interactions and developing strategies to selectively target them for therapeutic purposes, particularly in cancer. She pioneered widely used computational tools and AI-based approaches for modeling and designing peptide-protein interactions, combining them with experimental validation to generate active molecular binders.
About the Research
Ewing sarcoma is a rare and aggressive cancer that primarily affects children and young adults. While current treatments such as chemotherapy and surgery can cure some patients, outcomes remain poor, and there is no approved targeted therapy that directly addresses the molecular cause of this cancer. In most cases, Ewing sarcoma is driven by a single abnormal protein, called EWS/FLI1, created by a chromosomal rearrangement. This protein acts as an abnormal gene regulator that drives cancer growth. Because it lacks obvious binding sites, EWS/FLI1 has long been considered impossible to target directly with drugs.
This research proposes a new way to overcome this challenge. We have discovered that the EWS/FLI1 protein briefly exposes a hidden (“cryptic”) binding site when it naturally switches between monomer and dimer forms. By targeting this transient site, we aim to directly engage the cancer-driving protein itself. Using advanced AI-based design tools together with laboratory experiments, we will develop small peptide and peptide-like molecules that bind specifically to this hidden site. In the short term, these molecules could serve as highly specific markers for identifying Ewing sarcoma cells. In the longer term, they may be adapted to deliver targeted therapies or disrupt the activity of the cancer-driving protein.
This work brings together computational, chemical, biological, and clinical expertise to open new possibilities for diagnosing and treating Ewing sarcoma.
