Holger Wille

 

Research:

The general focus of my work is the structure of amyloids and other disease-related, misfolded proteins. In particular, I am interested in the infectious prion protein (PrPSc) and the structure-function relationship underlying its infectious nature. In recent years, mounting evidence has implicated prion-like mechanisms in other neurodegenerative diseases such as Alzheimer's, Parkinson's, and Lou Gehrig's disease. The mechanistic similarities and their molecular underpinnings represent interesting research avenues beyond the classical prion diseases. The scope of my current experimental approaches is centered on electron microscopy, three-dimensional reconstruction approaches, X-ray fiber diffraction, and other biochemical and biophysical methods.

 

Selected Publications:

A model-based prion vaccine protects a transgenic mouse line carrying a Gerstmann-Sträussler-Scheinker disease mutation. 

Fang A, Tang X, Fleming M, Tancowny B, Wang X, Wang Y, Daude N, Dorosh L, Fleck SC, Rathod V, Coustou V, Cervantes SA, Velásquez CD, Westaway D, Aiken J, McKenzie D, Telling G, Stepanova M, Saupe SJ, Siemer AB, Wille H (2026). Acta Neuropathologica 151(1):41.

Vaccination with structurally adapted fungal protein fibrils induces immunity to Parkinson’s disease.

Pesch, V, Flores-Fernandez, JM, Reithofer, S, Ma, L, Özdüzenciler, P, Busch, Y, Sriraman, A, Wang, YL, Amidian, S, Kroepel, CVM, Müller, L, Lien, Y, Rudtke, O, Frieg, B, Schröder, GF, Wille, H, and Tamgüney, G (2024). Brain, 147, 1644-1652.

Vaccines mimicking conformational epitopes on alpha-synuclein fibrils provide immunity to Parkinson's disease.

Ma, L, Reithofer, S, Pesch, V, Flores-Fernandez, JM, Sriraman, A, Duckering, C, Amidian, S, Özdüzenciler, P, Müller, L, Werner, K, Wille, H, and Tamgüney, G (2026). Brain, 149, published online.

 Rational design of structure-based vaccines targeting misfolded alpha-synuclein conformers of Parkinson’s disease and related disorders.
Flores-Fernandez, JM, Pesch, V, Sriraman, A, Chimal-Juarez, E, Amidian, S, Wang, X, Duckering, C, Fang, A, Reithofer, S, Ma, L, Cortez, LM, Sim, VL, Tamgüney, G & Wille, H 
Bioengineering & Translational Medicine (2024) 9, e10665.

The ultrastructure of infectious L-type bovine spongiform encephalopathy prions constrains molecular models.
Kamali-Jamil, R, Vázquez-Fernández, E, Tancowny, B, Rathod, V, Amidian, S, Wang, X, Tang, X, Fang, A, Senatore, A, Hornemann, S, Dudas, S, Aguzzi, A, Young, HS, Wille, H
PLoS Pathogens (2021) 17, e1009628

Full atomistic model of prion structure and conversion.
Spagnolli G, Rigoli M, Orioli S, Sevillano AM, Faccioli P, Wille H, Biasini E, Requena JR.
PLoS Pathogens (2019) Jul 11;15(7):e1007864. doi: 10.1371/journal.ppat.1007864. eCollection 2019 Jul.

The Structure of PrP^Sc Prions
Wille H, Requena JR.
Pathogens. (2018) Feb 7;7(1). pii: E20. doi: 10.3390/pathogens7010020. Review

Elucidating the structure of an infectious protein.
Zweckstetter, M, Requena, JR, Wille, H.
PLoS Pathogenss (2017) 13 Apr 13(4): e1006229.

The structural architecture of an infectious mammalian prion using electron cryomicroscopy.
Vázquez-Fernández, E, Vos, MR, Afanasyev, P, Cebey, L, Sevillano, AM, Vidal, E, Rosa, I, Renault, L, Ramos, A, Peters, PJ, Fernández, JJ, van Heel, M, Young, HS, Requena, JR, Wille, H. PLoS Pathogens (2016) Sep 8;12(9):e1005835