Design spin cluster for NMR signal amplification and quantum resonance sensing
To reveal “invisible” NMR signal of surfaces, active sites, and functional species in catalysis, molecular recognition and quantum materials using out of the box tools.
Spying on Molecular Action with Spins
The Han lab pushes the frontier of magnetic resonance to discover new chemistry principles in water and through control over the shaping and ordering of dynamic water. We use advanced magnetic resonance manipulation and control over the spatial organization of electron and nuclear spin clusters located on biomolecular surface, soft materials or nanomaterials to uncover their structure, the design rules for molecular recognition, and the surface structuring and dynamics of hydration water.
The development effort requires multiple research tools in the realm of physical chemistry broadly speaking. They include instrument development to achieve hyperpolarization and quantum resonance sensing, the design of precisely tuned electron and nuclear spin clusters, spin physic theory and simulations, and the dynamics and thermodynamics of solvation science to control biomolecular activity and directed assembly.
The Han lab is pushing the frontier of electron and nuclear spin magnetic resonance instrumentation and concepts in dynamic nuclear polarization (DNP) amplified nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR). We are motivated by the power of “Seeing is Believing”. Visualizing molecular interactions and materials interfaces, previously “invisible”, can fundamentally transform our ability to discover solutions, and almost as importantly, ask new questions.
Areas Of Research
Research in the Han Lab builds and employs state-of-the-art tools in magnetic resonance spectroscopy to advance our understanding in different subject areas, ranging from quantum sensing, solvation science, biophysics to neurodegenerative diseases.
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Water directed protein assembly for shape control and templated self-replication
To understand, control and engineer protein aggregation pathways, protein surface activity to protein liquid-liquid phase separation.
Water as a shape-shifting and active biological building block
To reveal long-standing questions on the structure and dynamics of water on proteins, membranes to catalyst support surfaces.
Publications
+ VIEW ALLStructure-specific Mini-Prion Model for Alzheimer’s Disease Tau Fibrils
V. Vijayan, G. E. Merz, K. Tsay, A. P. Longhini, S. Lobo, A. Quddus, K. L. S. Nakagawa, M. P. Vigers, A. A. Melo, E. Tse, J.-E. Shea, M. S. Shell, K. S. Kosik, D. R. Southworth, S. Han bioRxiv, (2025).
A critical discovery of the past decade is that tau protein fibrils adopt disease-specific hallmark structures in each tauopathy. The faithful generation of synthetic fibrils adopting hallmark structures that can serve as targets for developing diagnostic and/or therapeutic strategies remains a grand challenge. We report on a rational design of synthetic fibrils built of a short peptide that adopts a critical structural motif in tauopathy fibrils found in Alzheimer’s Disease (AD) and Chronic Traumatic Encephalopathy (CTE). They serve as minimal prions with exquisite seeding competency, in vitro and in tau biosensor cells, for recruiting tau constructs ten times larger its size en route to AD or CTE fibril structures. We demonstrate that the generation of AD and CTE-like fibril structures is dramatically catalyzed in the presence of mini-AD prions and further influenced by salt composition in solution. Double Electron-Electron Resonance studies confirmed the preservation of AD-like folds across multi-generational seeding. Fibrils formed with the full AD/CTE-like core show strong seeding competency, with their templating effect dominating over the choice of salt composition that tunes the initial selection of AD- and CTE-like fibril populations. The mini-AD prions serve as a potent catalyst with templating capabilities that offer a novel strategy to design pathological tau fibril models.
Hydraulic Activation of the AsLOV2 photoreceptor
S. Maity, J. Sheppard, H. Russell, C. Han, L. Epstein, B. A. Johnson, B. Price, R. Han, L. R. Potnuru, J. Cui, M. S. Sherwin, J.-E. Shea, J. E. Lovett, K. H. Gardner, and S. Han bioRxiv, (2025).
How proteins transduce environmental signals into mechanical motion remains a central question in biology. This study tests the hypothesis that blue light activation of AsLOV2 gives rise to concerted water movement that induce protein conformational extensions. Using electron and nuclear magnetic resonance spectroscopy, along with atomistic molecular dynamics simulations at high pressure, we find that activation, whether initiated by blue light or high pressure, is accompanied by selective expulsion of low-entropy, tetrahedrally coordinated “wrap” water from hydrophobic regions of the protein. These findings suggest that interfacial water serves as functional constituents to help reshape the protein’s free energy landscape during activation. Our study highlights hydration water as an active medium with the capacity to drive long-range conformational changes underlying protein mechanics and offers a new conceptual understanding for engineering externally controllable protein actuators for biomedical studies to smart materials.
Water-directed pinning is key to tau prion formation
M. P. Vigers, S. Lobo, S. Najafi, A. Dubose, K. Tsay, P. Ganguly, A. P. Longhini, Y. Jin, S. K. Buratto, K. S. Kosik, M. S. Shell, J. Shea, and S. Han Proc. Natl. Acad. Sci. U.S.A., 122 (2025), e2421391122.
https://doi.org/10.1073/pnas.2421391122. PMID: 40294272. PMCID: PMC12067210.
Featured in Northwestern Now, Phys.org, & Le Monde.
Featured in Northwestern Now, Phys.org, & Le Monde.
Tau forms fibrillar aggregates that are pathological hallmarks of a family of neurodegenerative diseases known as tauopathies. The synthetic replication of disease-specific fibril structures is a critical gap for developing diagnostic and therapeutic tools. This study debuts a strategy of identifying a critical and minimal folding motif in fibrils characteristic of tauopathies and generating seeding-competent fibrils from the isolated tau peptides. The 19-residue jR2R3 peptide (295 to 313) which spans the R2/R3 splice junction of tau, and includes the P301L mutation, is one such peptide that forms prion-competent fibrils. This tau fragment contains the hydrophobic VQIVYK hexapeptide that is part of the core of all known pathological tau fibril structures and an intramolecular counterstrand that stabilizes the strand–loop–strand (SLS) motif observed in 4R tauopathy fibrils. This study shows that P301L exhibits a duality of effects: it lowers the barrier for the peptide to adopt aggregation-prone conformations and enhances the local structuring of water around the mutation site to facilitate site-directed pinning and dewetting around sites 300-301 to achieve in-register stacking of tau to cross β-sheets. We solved a 3 Å cryo-EM structure of jR2R3-P301L fibrils in which each protofilament layer contains two jR2R3-P301L copies, of which one adopts a SLS fold found in 4R tauopathies and the other wraps around the SLS fold to stabilize it, reminiscent of the three- and fourfold structures observed in 4R tauopathies. These jR2R3-P301L fibrils are competent to template full-length 4R tau in a prion-like manner.
Recent News
+ VIEW ALL
Hoang passed his candidacy exam!
June 27, 2025
Martyna Judd Receives JMR/JMRO Award at ENC-ISMAR 2025
April 21, 2025
Interested in joining the Han research group? Reach us at han-ofc@northwestern.edu
Follow us at @songihanlab