Data-driven modeling of estrogen receptor

The estrogen receptor (ER or ERα) plays a fundamental role in breast cancer through complex molecular mechanisms involving its N-terminal transactivation domain (NTD), DNA-binding domain (DBD), and ligand- binding domain (LBD). Understanding their structural dynamics is crucial for developing next-generation ER- targeted therapeutics. Our research employs advanced biophysical techniques to decode two fundamental aspects of ER regulation. Project-1 will characterize the structural properties of the NTD through nuclear magnetic resonance spectroscopy and small-angle X-ray scattering (SAXS), generating comprehensive structural insights. Project-2 will examine the dynamic interactions between DBD and LBD using cryo-electron microscopy combined with solution-state SAXS analysis, revealing how various factors influence domain communication. These studies will establish a detailed framework for understanding ER regulation in normal and disease states, with broad implications for the nuclear receptor family. Our data-driven computational strategy will illuminate new molecular mechanisms underlying receptor function. The methodological advances from this research will enhance our understanding of protein dynamics and domain interactions across the nuclear receptor family, potentially leading to innovative therapeutic strategies for hormone-dependent cancers. Project Number: 1R35GM161242-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: Sichun Yang | Institution: CASE WESTERN RESERVE UNIVERSITY, CLEVELAND, OH | Award Amount: $431,750 | Activity Code: R35 | Study Section: Maximizing Investigators' Research Award B Study Section[MRAB] View on NIH RePORTER: https://reporter.nih.gov/project-details/11259233