Dr. Jinghui Luo

My group aims to establish a multiscale framework to understand how intrinsically disordered amyloid proteins transition from monomers to nanoclusters and oligomers, and how these species are ultimately cleared in living systems, while simultaneously developing therapeutic strategies to interfere with these transitions. Using time-resolved SAXS, we will characterize the early conformational compaction and nanocluster formation of disordered proteins at the nanoscopic scale, revealing the structural pathways that lead to oligomer and condensate formation. Nanopore engineering and single-molecule trapping will then provide molecular-level insight into the structure, dynamics, and membrane interactions of monomers, oligomers and nanoclusters, allowing us to resolve heterogeneous populations and their functional properties. In parallel, we will develop and screen small molecules and peptides designed to modulate or redirect these assembly pathways, for example by stabilizing non-toxic states, preventing toxic oligomer formation, promoting nanocluster formation, or enhancing protein clearance. Finally, using C. elegans models, we will investigate how different aggregate species are processed by cellular degradation pathways such as autophagy and the proteasome, and determine how candidate compounds influence toxicity, aggregation state, and degradation in vivo. By integrating structural biology, single-molecule biophysics, chemical biology, and in vivo models, this project links protein disorder, nanocluster assembly, molecular structure, therapeutic intervention, and biological clearance, providing a comprehensive framework for understanding and targeting early aggregation processes in neurodegenerative diseases.

Multiscale Biophysics of Neurodegeneration

• Wanjing Lai (2025, exchange student from HongKong University)
• Chang Liu (2021-2025, Ph.D student, next destination: Helsinki University)
• Dimitris Lymperopoulos, (2024, Trainee, next destination: Freiburg University)
• Miriam Pinto, (2023-2024, Trainee, next destination: Roche)
• Ariane Melissa Schwitter,  (2024, Guest Ph.D student from the University of Tokyo)
• Sigrid Kirss,  (2024, Guest Ph.D student from Tallin University of Technology)
• Urte Venclovaite, (2023, Summer intern from Vilnius University)
• Duan Fangyuan, (2022, Guest Ph.D student from Harbin Institute of Technology)
• Jinming Wu, (2018-2022, Ph.D student, next destination: Lund University)
• Hongzhi Wang, (2018-2021, Ph.D student, next destination: Chinese Academy of Sciences)
• Hegne Pupart, (2018, Summer intern, next destination: Ph.D student at Tallinn University of Technology)

2026

• Alzheimer's Aβ Catalyzes Tau Phase Separation and Aggregation via Early Nanocluster Solubilization.
  Sun X, Tang Y, Wang X, Pereira Curia G, Sternke-Hoffmann R, Mörman C, Gerez JA, Riek R, Wei G, Luo J*.
  Nature Communications (2026). DOI: 10.1038/s41467-026-70083-1. (in press)
• Time-Resolved SAXS Reveals Distinct Millisecond Metal-Induced Conformational Dynamics of Monomeric α-Synuclein.
  Sternke-Hoffmann R, Pinto MDS, Wang X, Luo J*.
  Advanced Science (2026): e12293.
• Protein-Driven Copper Redox Regulation: Uncovering the Role of Disulphide Bonds and Allosteric Modulation.
  Sternke-Hoffmann R, Liu C, Wang X, Pupart H, Sun X, Dreiser JG, Palumaa P, Liao Q, Krack M, Luo J*.
  Angewandte Chemie International Edition (2026): e19673. DOI: 10.1002/anie.202519673.
• Structural Insights into Copper and Zinc Binding to Tau Protein and the Impact of Metal Binding on Amyloid Aggregation.
  Juárez-Romero GU, Sun X, Gerez JA, Den Auwer C, Landrot G, Nachtegaal M, Riek R, Luo J, Quintanar L.
  Chemical Science (2026). DOI: 10.1039/d5sc08604c. (in press)
• Residue-Specific Modulation of Aggregation-Associated Interactions by Spermine in Tau, α-Synuclein, and Aβ40.
  Saha D, Xun S, Yang W, Luo J, Zheng W.
  JACS Au (2026). DOI: 10.1021/jacsau.6c00126. (in press)

2025

• Structural Insights and Functional Dynamics of Beta-Lactoglobulin Fibrils.
  Sternke-Hoffmann R, Rhyner D, Terashi G, Qureshi B, Riek R, Greenwald J, Kihara D, Lutz-Bueno V, Luo J*.
  Nano Letters (2025) 25:16146–16153.
• Spermine Modulation of Alzheimer’s Tau and Parkinson’s α-Synuclein: Implications for Biomolecular Condensation and Neurodegeneration.
  Sun X, Saha D, Wang X, Mörman C, Sternke-Hoffmann R, Gerez J, Herranz F, Riek R, Zheng W, Luo J*.
  Nature Communications (2025) 16(1):10239.
• Synthetic Chaperone Based on Hsp90-Tau Interaction Inhibits Tau Aggregation and Rescues Physiological Tau-Microtubule Interaction.
  Di Lorenzo D, Bisi N, Kaffy J, Ramirez LM, Zweckstetter M, Lequin O, Garfagnini I, Luo J, Hannappel Y, Ennen I, Dodero V, Sewald N, Gelmi ML, Tonali N, Brandt R.
  Nature Communications (2025) 16:8756.
• LL-37 and Its Truncated Fragments Modulate Amyloid-β Dynamics, Aggregation and Toxicity Through Hetero-Oligomer and Cluster Formation.
  Wang X, Österlund N, Pereira Curia G, Mörman C, Sternke-Hoffmann R, Ilag LL, Gräslund A, Wang G, Luo J*.
  Angewandte Chemie International Edition (2025): e202516241.
• Chaperone-Mediated Regulation of Tau Phase Separation, Fibrillation, and Toxicity.
  Mörman C, Leppert A, Pizzirusso G, Zheng Z, Sun X, Kumar R, Biverstål H, Landreh M, Johansson J, Arroyo-Garcia LE, Luo J, Chen G, Abelein A.
  Journal of the American Chemical Society (2025) 147(27):23504–23518.

• Unveiling the Assembly Transition of Diphenylalanine and Its Analogs: From Oligomer Equilibrium to Nanocluster Formation.
  Liu C, Dan Y, Yun J, Adler-Abramovich L, Luo J*.
  ACS Nano (2025) 19(13):13250–13263.

   

2024

• Pathogenic mutation ΔK280 promotes hydrophobic interactions involving microtubule-binding domain and enhances liquid-liquid phase separation of tau.
  Chen Y, Sun X, Tang Y, Tan Y, Guo C, Pan T, Zhang X, Luo J*, Wei G*.
  Small (2024): e2406429. DOI: 10.1002/smll.202406429.
• Phase Separation and Aggregation of α-Synuclein Diverge at Different Salt Conditions.
  Sternke-Hoffmann R, Sun X, Menzel A, Pinto MDS, Venclovaite U, Wördehoff M, Hoyer W, Zheng W*, Luo J*.
  Advanced Science (2024): e2308279. DOI:10.1002/advs.202308279.
• Self-Adaptive Synthesis of Non-Covalent Crosslinkers while Folding Single-Chain Polymers.
  Qi D, Shi X, Lin C, Holzhausen F, Ville L, Su X, Luo J, Pitkänen L, Zhu Y, Rosenholm J, Jalkanen S, Li J.
  Angewandte Chemie International Edition (2024): e202408670. DOI:10.1002/anie.202408670.
• Channel Activities of the Full-Length Prion and Truncated Proteins.
  Wu J, Wang X, Lakkaraju A, Sternke-Hoffmann R, Qureshi BM, Aguzzi A, Luo J*.
  ACS Chemical Neuroscience (2024) 15(1):98–107. DOI:10.1021/acschemneuro.3c00412.

• Visualizing Alpha-Synuclein and Iron Deposition in M83 Mouse Model of Parkinson's Disease In Vivo.
  Straumann N, Combes BF, Dean Ben XL, Sternke-Hoffmann R, Gerez JA, Dias I, Chen Z, Watts B, Rostami I, Shi K, Rominger A, Baumann CR, Luo J, Noain D, Nitsch RM, Okamura N, Razansky D, Ni R.
  Brain Pathology (2024): e13288. DOI:10.1111/bpa.13288.

   

2023

• Oligomer Dynamics of LL-37 Truncated Fragments Probed by α-Hemolysin Pore and Molecular Simulations.
  Liu C#, Henning-Knechtel A#, Österlund N, Wu J, Wang G, Gräslund RAO, Kirmizialtin S, Luo J*.
  Small (2023): e2206232.
• Protein Oligomer Engineering: A New Frontier for Studying Protein Structure, Function, and Toxicity.
  Liu C, Luo J*.
  Angewandte Chemie (2023): e202216480.
• Cross Interactions between Apolipoprotein E and Amyloid Proteins in Neurodegenerative Diseases.
  Loch RA#, Wang H#, Perálvarez Marín A, Berger P, Nielsen H, Chroni A, Luo J*.
  Computational and Structural Biotechnology Journal (2023) 21:1189–1204.

• Single-Molecule Nanopore Dielectrophoretic Trapping of α-Synuclein with Lipid Membranes.
  Wu J, Yamashita T, Hamilton AD, Thompson S, Luo J*.
  Cell Reports Physical Science (2023) 4:101243.

   

2022

• Multivariate Effects of pH, Salt, and Zn²⁺ Ions on Aβ40 Fibrillation.
  Wang H, Wu J, Sternke-Hoffmann R, Zheng W, Mörman C, Luo J*.
  Communications Chemistry (2022) 5:171.
• Identifying the Role of Co-Aggregation of Alzheimer’s Amyloid-Beta with Amorphous Protein Aggregates of Non-Amyloid Proteins.
  Wu J, Österlund N, Wang H, Sternke-Hoffmann R, Pupart H, Ilag LL, Gräslund A, Luo J*.
  Cell Reports Physical Science (2022) 3:101028.
• Evaluation of Zn²⁺- and Cu²⁺-Binding Affinities of Native Cu,Zn-SOD1 and Its G93A Mutant by LC-ICP MS.
  Smirnova J, Gavrilova J, Noormägi A, Valmsen K, Pupart H, Luo J, Tõugu V, Palumaa P.
  Molecules (2022) 27:3160.
• Cu²⁺ Ions Modulate the Interaction Between α-Synuclein and Lipid Membranes.
  Wang H, Mörman C, Sternke-Hoffmann R, Huang CY, Prota A, Ma P, Luo J*.
  Journal of Inorganic Biochemistry (2022) 236:111945.

• Rationally Designed Helical Peptidomimetics Disrupt α-Synuclein Fibrillation.
  Bavinton CE, Sternke-Hoffmann R, Yamashita T, Knipe PC, Hamilton AD, Luo J*, Thompson S*.
  Chemical Communications (2022) 58:5132–5135.

   

2021

• Editorial: The Biochemistry of Amyloids in Neurodegenerative Diseases, Volume I.
  Gomes C*, Hoyer W*, Luo J*.
  Frontiers in Neuroscience (2021): 819481.
• Amyloid-Beta–Copper Interaction Studied by Simultaneous Nitrogen K and Copper L₂,₃-Edge Soft X-ray Absorption Spectroscopy.
  Luo J*, Wang H, Wu J, Romankov V, Daffe N, Dreiser J*.
  iScience (2021) 24:103465.
• Cryo-Electron Microscopy Imaging of Alzheimer's Amyloid-Beta 42 Oligomer Displayed on a Functionally and Structurally Relevant Scaffold.
  Wu J, Blum TB, Farrell DP, DiMaio F, Abrahams JP, Luo J*.
  Angewandte Chemie International Edition (2021).

• ATP Impedes the Inhibitory Effect of Hsp90 on Aβ40 Fibrillation.
  Wang H, Lallemang M, Hermann B, Wallin C, Loch R, Blanc A, Balzer BN, Hugel T, Luo J*.
  Journal of Molecular Biology (2021) 433:166717.

   

2020

• Antimicrobial Peptide Mimetics Based on a Diphenylacetylene Scaffold: Synthesis, Conformational Analysis, and Activity.
  Peacock H, Henriques ST, Benfield AH, Elliott AG, Luo J, Luccarelli J, Nagano M, Craik D, Hamilton AD.
  ChemMedChem (2020) 15:1932–1939.

• Single-Molecule Studies of Amyloid Proteins: From Biophysical Properties to Diagnostic Perspectives.
  Wu J, Cao C, Loch RA, Tiiman A, Luo J*.
  Quarterly Reviews of Biophysics (2020) 53:e12.

   

2019

• Nuclear Pore Membrane Proteins Self-Assemble into Nanopores.
  Panatala R, Barbato S, Kozai T, Luo J, Kapinos LE, Lim RYH.
  Biochemistry (2019) 58:484.

   

2018

• Membrane-Mimetic Systems for Biophysical Studies of the Amyloid-Beta Peptide.
  Österlund N, Luo J, Wärmländer SKTS, Gräslund A.
  Biochimica et Biophysica Acta – Proteins and Proteomics (2018).

• The Neuronal Tau Protein Blocks In Vitro Fibrillation of the Amyloid-Beta Peptide at the Oligomeric Stage.
  Wallin C, Hiruma Y, Wärmländer SKTS, Huvent I, Jarvet J, Abrahams J, Gräslund A, Lippens G, Luo J*.
  Journal of the American Chemical Society (2018) 140:8138.

   

2017

• Alzheimer's Disease and Cigarette Smoke Components: Effects on Amyloid-Beta Peptide Aggregation.
  Wallin C, Sholts SB, Österlund N, Luo J, Jarvet J, Roos PM, Ilag L, Gräslund A, Wärmländer SKTS.
  Scientific Reports (2017) 7:14423.

• Maleimido-Proxyl as an EPR Spin Label for Evaluation of Conformational Changes of Albumin.
  Pavicevic A, Luo J, Popovic-Bijelic A, Mojovic M.
  European Biophysics Journal (2017) 46:773.

   

2016

• Characterization of Mn(II) Ion Binding to the Amyloid-Beta Peptide in Alzheimer's Disease.
  Wallin C et al., Luo J.
  Journal of Trace Elements in Medicine and Biology (2016).
• Cross-Interactions Between the Alzheimer Disease Amyloid-β Peptide and Other Amyloid Proteins.
  Luo J*, Wärmländer SKTS, Gräslund A, Abrahams J.
  Journal of Biological Chemistry (2016) 291:16485.
• Non-Covalent S···O Interactions Control Conformation in a Scaffold that Disrupts IAPP Fibrillation.
  Peacock H, Luo J, Yamashita T, Luccarelli J, Thompson S, Hamilton AD.
  Chemical Science (2016) 7:6435.
• Reciprocal Molecular Interactions Between Aβ Peptide and Insulin.
  Luo J, Wärmländer SKTS, Gräslund A, Abrahams J.
  ACS Chemical Neuroscience (2016) 7:269.
• Specific Binding of Cu(II) Ions to Amyloid-Beta Peptides Generates ROS.
  Tiiman A et al., Luo J.
  Journal of Alzheimer's Disease (2016) 54:971.

• The Amyloid-Beta Peptide in Amyloid Formation Processes.
  Wallin C, Luo J, Jarvet J, Wärmländer SKTS, Gräslund A.
  Israel Journal of Chemistry (2016) 57:674.

   

2014

• Alzheimer Peptides Aggregate into Transient Nanoglobules That Nucleate Fibrils.
  Luo J, Wärmländer SKTS, Gräslund A, Abrahams J.
  Biochemistry (2014) 53:6302.
• Cyclic Peptides as Inhibitors of Amyloid Fibrillation.
  Luo J, Abrahams J.
  Chemistry – A European Journal (2014) 20:2410.
• Endogenous Polyamines Reduce the Toxicity of Soluble Aβ Peptide Aggregates.
  Luo J, Mohammed I, Wärmländer SKTS, Hiruma Y, Gräslund A, Abrahams J.
  Biomacromolecules (2014) 15:1985.
• Non-Chaperone Proteins Can Inhibit Aggregation and Cytotoxicity of Amyloid Beta Peptide.
  Luo J, Wärmländer SKTS, Gräslund A, Abrahams J.
  Journal of Biological Chemistry (2014) 289:27766.
• The Abeta Peptide Forms Non-Amyloid Fibrils in the Presence of Carbon Nanotubes.
  Luo J, Wärmländer SKTS, Yu C, Muhammad K, Gräslund A, Abrahams JP.
  Nanoscale (2014) 6:6720.

• The Hairpin Conformation of the Amyloid Beta Peptide Is an Important Structural Motif.
  Abelein A et al., Luo J.
  JBIC Journal of Biological Inorganic Chemistry (2014) 19:623.

   

2013

• An Efficient Nanolitre-Volume Multi-Channel Device for Highly Viscous Materials Used in Membrane Protein Crystallization.
  Luo J, Zwier R, Abrahams J.
  Journal of Applied Crystallography (2013) 46:829.
• Biophysical Studies of the Amyloid β-Peptide: Interactions with Metal Ions and Small Molecules.
  Wärmländer S, Tiiman A, Abelein A, Luo J, Jarvet J, Söderberg KL, Danielsson J, Gräslund A.
  ChemBioChem (2013) 14:1692.
• Cellular Polyamines Promote Amyloid-Beta Peptide Fibrillation.
  Luo J, Yu C, Yu H, Borstnar R, Kamerlin SCL, Gräslund A, Abrahams J, Wärmländer SKTS.
  ACS Chemical Neuroscience (2013) 4:454.
• Exploiting preQ1 Riboswitches to Regulate Ribosomal Frameshifting.
  Yu C, Luo J, Iwata-Reuyl D, Olsthoorn RCL.
  ACS Chemical Biology (2013) 8:733.
• Human Lysozyme Inhibits the In Vitro Aggregation of Aβ Peptides.
  Luo J, Wärmländer SKTS, Gräslund A, Abrahams J.
  Chemical Communications (2013) 49:6507.

• Inhibiting and Reversing Amyloid-Beta Peptide Fibril Formation with Gramicidin S Analogues.
  Luo J, Otero JM, Yu C, Wärmländer SKTS, Gräslund A, Overhand M, Abrahams J.
  Chemistry – A European Journal (2013) 19:17338.

   

2012

• Catalytic Promiscuity in Pseudomonas aeruginosa Arylsulfatase.
  Luo J, van Loo B, Kamerlin SCL.
  FEBS Letters (2012) 586:1622.
• Conformation Effects of CpG Methylation on Single-Stranded DNA Oligonucleotides.
  Taqi M et al., Luo J.
  PLOS ONE (2012) 7:e39605.

• Examining the Promiscuous Phosphatase Activity of Arylsulfatase.
  Luo J, van Loo B, Kamerlin SCL.
  Proteins: Structure, Function, and Bioinformatics (2012) 80:1211.

   

2011

• A Straightforward Method for Introducing Human Hair as a Nucleant into Crystallization Trials.
  Nederlof I et al., Luo J.
  Crystal Growth & Design (2011) 11:1170.
• Inhibition of Chlamydial Ribonucleotide Reductase by C-Terminal Peptides.
  Öhrström M et al., Luo J.
  Journal of Peptide Science (2011) 17:756.
• Ribonucleotide Reductase Inhibition by Metal Complexes of Triapine.
  Popovic-Bijelic A et al., Luo J.
  Journal of Inorganic Biochemistry (2011) 105:1422.

• Ribonucleotide Reductase Inhibition by p-Alkoxyphenols.
  Luo J, Gräslund A.
  Archives of Biochemistry and Biophysics (2011) 516:29.

   

2010

• In Silico Analysis of the Apolipoprotein E and the Amyloid β Peptide Interaction.
  Luo J, Maréchal JD, Wärmländer S, Gräslund A, Perálvarez-Marín A.
  PLOS Computational Biology (2010) 6:e1000663.