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. Our research is primarily focused on understanding the molecular causes of neurodegenerative disease, protein misfolding and protein deposition diseases. We are part of the Department of Structural Biology, and affiliated with the Center for Protein Conformational Diseases, Pittsburgh Brain Institute, Pitt/CMU Molecular Biophysics & Structural Biology PhD program, and MSTP MD/PhD program.
We use ssNMR spectroscopy 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, which are mutated in Huntington’s Disease (HD), various ataxias and other diseases. Through our mechanistic and structural studies we aim to further our understanding of the disease-causing processes and thus enable the design of new treatment strategies for these kinds of incurable diseases.
We also 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 a NIH-funded research project, we investigate 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 develop new methods in ssNMR for its biological application to protein aggregates, membranes and membrane proteins. We make use of ultrafast MAS methods, high-field multidimensional MAS ssNMR, oriented ssNMR, as well as in silico simulations. Our employ dedicated high-field ssNMR instruments housed in the Structural Biology NMR facility.
(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)
- 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]