Welcome to the website of the Van der Wel research group. We specialize in the use of biological solid-state NMR (ssNMR) spectroscopy, which we use to further our understanding of the molecular origins of diseases ranging from cancer to Huntington’s Disease.
We use ssNMR to determine the molecular structure and dynamics of proteins and other biomolecules. It is a particularly powerful for the study of protein misfolding and aggregation, which are the hallmarks of many neurodegenerative diseases. In our studies, we determine the structure of protein deposits, and also study how they form. A current focus is on the misfolding of expanded polyglutamine proteins including huntingtin, which is mutated in Huntington’s Disease (HD).
We also use ssNMR to study the interplay between lipid membranes and membrane-binding proteins. This is often a two-way process, where proteins modulate membrane structure and membranes modulate protein structure and function. We are currently investigating the protein-lipid interactions that are critical in the early stages of mitochondrial apoptosis – a process that is responsible for neurodegeneration in HD and other diseases.
The links to the right provide additional background on our research topics and techniques.
Questions? Interested in reprints or collaboration? Please contact us!
(see here for a complete listing)
- Huntingtin exon 1 fibrils feature an interdigitated β-hairpin-based polyglutamine core. Hoop, C.L., Lin, H.-K., Kar, K., Magyarfalvi, G., Lamley, J., Boatz, J.C., Mandal, A., Lewandowski, J., Wetzel, R., Van der Wel, P.C.A. (2016) Proc. Natl. Acad. Sci. USA. in press (At journal)
- Structural changes and pro-apoptotic peroxidase activity of cardiolipin-bound mitochondrial cytochrome c. Mandal, A., Hoop, C.L., DeLucia, M., Kodali, R., Kagan, V., Ahn, J., Van der Wel, P.C.A.* (2015) Biophys. J. 109(9): 1873–1884 (FREE ACCESS)
- Polyglutamine amyloid core boundaries and flanking domain dynamics in huntingtin fragment fibrils determined by solid-state NMR. Hoop, C.L., Lin, H.-K., Kar, K., Hou, Z., Poirier, M.A., Wetzel, R., and Van der Wel, P.C.A.* (2014) Biochemistry, (DOI)
- Lipid Dynamics and Protein-Lipid Interactions in Integral Membrane Proteins: Insights from Solid-State NMR. Van der Wel, P.C.A.* (2014) eMagRes. 3: 111–118 (DOI) (PDF download)
- D-polyglutamine amyloid recruits L-polyglutamine monomers and kills cells. Kar, K., Arduini, I., Drombosky, K.W., Van der Wel, P.C.A.*, Wetzel, R.* (2014) J Mol Biol. 426(4): 816–29 (DOI)
- Spinning-rate encoded chemical shift correlations from rotational resonance solid-state NMR experiments.Li, J., and Van der Wel, P.C.A.* (2013) J. Mag. Reson. 230:117-124 [at journal] [DOI]
- β-hairpin-mediated nucleation of polyglutamine amyloid formation.Kar, K., Hoop, C.L., Drombosky, K.W., Baker, M.A., Kodali, R., Arduini, I., Van der Wel, P.C.A., Horne, W.S., and Wetzel, R. (2013) J. Mol. Biol., 425(7):1-45 [DOI]
- Structural Characterization of the Caveolin Scaffolding Domain in Association with Cholesterol-Rich Membranes.Hoop, C.L.#, Sivanandam, V.N.#, Kodali, R., Srnec, M.N., Van der Wel, P.C.A. (2012) Biochemistry, 51(1):90–9 [DOI] [PubMed]
- Amyloid-like fibrils from a domain-swapping protein feature a parallel, in-register conformation without native-like interactions.Li, J.; Hoop, C.L.; Kodali, R.; Sivanandam, V.N.,; and Van der Wel, P.C.A.* (2011) J. Biol. Chem. 286(33): 28988-95 [at journal][PubMed]
- The Aggregation-Enhancing Huntingtin N-terminus is Helical in Amyloid FibrilsSivanandam, V.N., Jayaraman, M., Hoop, C.L., Kodali, R., Wetzel, R., and Van der Wel, P.C.A. (2011) J. Am. Chem. Soc. 133(12): 4558–4566 [at journal]
- Structural Characterization of GNNQQNY Amyloid Fibrils by Magic Angle Spinning NMR.Van der Wel, P.C.A.; Lewandowski, J.R., and Griffin, R.G. (2010) Biochemistry 49(44): 9457–9469 [on-line] [PubMed]
- Observation of a low-temperature, dynamically driven structural transition in a polypeptide by solid state NMR spectroscopyBajaj, V.S.; Van der Wel, P.C.A., and Griffin, R.G. (2009) J. Am. Chem. Soc. 131 (1): 118–128 Online
- Dynamic nuclear polarization of amyloidogenic peptide nanocrystals: GNNQQNY, a core segment of the yeast prion protein Sup35p.Van der Wel, P.C.A.; Hu, K.-N.; Lewandowski, J.R., and Griffin, R.G. (2006) J. Am. Chem. Soc. 128(33):10840-10846 [Abstract] [DOI]
- Tryptophan-anchored transmembrane peptides promote formation of nonlamellar phases in phosphatidylethanolamine model membranes in a mismatch-dependent manner.Van der Wel, P.C.A.; Pott, T.; Morein, S.; Greathouse, D.V.; Koeppe II, R.E., and Killian, J.A. (2000) Biochemistry 39: 3124-33. [Abstract] [DOI]