Research

Professor Donghan Lee

Professor Donghan Lee is a prominent researcher specializing in Biomolecular NMR (Nuclear Magnetic Resonance) Spectroscopy. Our research focuses on developing innovative NMR methods to elucidate the structural dynamics and kinetics of proteins, particularly those involved in human diseases like cancer and neurodegeneration. By bridging the gap between static structures and functional motions, we work provides critical insights into how proteins recognize their partners and how these processes can be modulated for therapeutic purposes.

Core Research Areas

1. Advanced NMR Methodology Development

A significant portion of we work involves pushing the technical limits of NMR to observe phenomena previously considered "invisible."

• Supra-τc Window: Developing techniques to measure protein dynamics in the microsecond to millisecond range, filling the gap between fast (picosecond) and slow (second) timescales.

• Relaxation Dispersion: Enhancing CPMG (Carr-Purcell-Meiboom-Gill) and R1ρ experiments to detect high-energy "excited states" of proteins that are crucial for ligand binding but exist only transiently.

• Deep Learning in NMR: Integrating AI to improve the analysis of time-domain signals, making NMR data processing more robust and efficient.

2. Intrinsically Disordered Proteins (IDPs) and Cancer

He investigates proteins that lack a fixed 3D structure, such as the p53 transactivation domain and 4EBP1.

• p53 Dynamics: Exploring the multi-timescale structural fluctuations of p53, a master tumor suppressor, to understand its interaction with various signaling partners.

• Targeting MdmX-p53: Developing small molecules to disrupt the interaction between p53 and its negative regulators (MdmX/Mdm2) to reactivate natural anti-cancer mechanisms.

3. Protein Recognition and Allostery

Professor Lee studies how proteins "choose" their binding partners and how signals are transmitted through protein backbones.

• Conformational Shuffling: Investigating how proteins like Ubiquitin utilize collective motions to navigate between different conformations, known as "population shuffling."

• Allosteric Networks: Mapping how binding at one site (e.g., Guanylate Kinase) influences activity at a distant site through coupled motions.

4. Drug Discovery and Therapeutic Targets

Applying structural biology to identify and optimize new drug candidates.

• Thrombocytopenia: Researching inhibitors for Biliverdin IXβ Reductase B (BLVRB) as a novel therapeutic target for blood-related disorders.

• FDA Drug Repositioning: Using NMR-based screens to find new uses for existing drugs, such as identifying inhibitors for phosphatase PTP4A3 (PRL-3).