Welcome to the website of the Van der Wel research group. We specialize in state-of-the-art 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 as it allows us to perform unique structural studies of protein misfolding and aggregation, which are the hallmarks of many neurodegenerative diseases. We determine the structure of protein deposits, as well as the mechanism of aggregate formation. In one of our current NIH-funded projects, we are studying the misfolding of expanded polyglutamine proteins including huntingtin, which is mutated in Huntington’s Disease (HD), various ataxias and other diseases. These mechanistic and structural studies are designed to further our understanding of the disease-causing processes and thus enable the design of new treatment strategies for these incurable diseases.
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. In another project, we are investigating the protein-lipid interactions that are critical in the early stages of mitochondrial apoptosis. Part of our interest in this process stems from the fact that it is plays a critical role in the neurodegeneration in HD and related diseases. Thus, we aim to obtain new mechanistic insights that may pave the way for possible new treatment strategies.
We also have an interest in the development of new methods in ssNMR and its biological application to protein aggregates, membranes and membrane proteins. This work includes the use of ultrafast MAS methods, high-field multidimensional MAS ssNMR, oriented ssNMR, as well as in silico simulations. We make use of our world-class NMR facilities with multiple dedicated ssNMR spectrometers.
(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 (At journal)
- 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)
- 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]
- 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 Fibrils. Sivanandam, 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]
- 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]