Patrick van der Wel
The Van der Wel group uses solid state NMR (ssNMR) spectroscopy and other experiments to study protein aggregation and protein-lipid interactions. With our structural studies we provide new insights into the molecular mechanisms that cause disease, with the aim of helping the development of treatments that target disease causes rather than symptoms. Using advanced magic angle spinning (MAS) ssNMR, we elucidate the protein misfolding and aggregation that underlies Huntington’s Disease and other protein deposition disorders. We also use ssNMR to study the structure of membrane-associated proteins, and the membranes to which they are bound. We are studying mitochondrial protein-lipid interactions that play a pivotal role in mitochondrial dysfunction and apoptosis, and thus are implicated in diseases ranging from cancer to neurodegenerative disease.
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Education & Training
Utrecht University, Utrecht, the Netherlands
B.S., 1996 in Chemistry
University of Arkansas, Fayetteville, AR
Ph.D., 2002 in Biochemistry, Advisor: Prof. Roger E. Koeppe II
Massachusetts Institute of Technology, Cambridge, MA
Postdoctoral Fellow 2003 – 2008 in Biochemistry and solid-state NMR, Advisor: Prof. Robert G. Griffin
Awards & Honors
2013 Eastern Analytical Symposium (EAS) New Faculty Award in NMR Spectroscopy
Sivanandam, V.N, Jayaraman, M., Hoop, C.L., Kodali, R., Wetzel, R., and Van der Wel, P.C.A. The aggregation-enhancing Huntingtin N-terminus is helical in amyloid fibrils. J. Am. Chem. Soc. 2011; 133(12): 4558–4566
Li, J., Hoop, C.L., Kodali, R., Sivanandam, V.N., and Van der Wel, P.C.A. Amyloid-like fibrils from a domain-swapping protein feature a parallel, in-register conformation without native-like interactions. J. Biol Chem. 2011; 286(33):28988-28995
Hoop, C.L.; Sivanandam, V.N., Kodali, R., Srnec, M.N., and Van der Wel, P.C.A. Structural Characterization of the Caveolin Scaffolding Domain in Association with Cholesterol-Rich Membranes. Biochemistry. 2012; 51(1):90-99.
Kar, K., Arduini, I., Drombosky, K. W., Van der Wel, P. C. A.#, and Wetzel, R. # D-polyglutamine amyloid recruits L-polyglutamine monomers and kills cells. J Mol Biol 2014; 426(4): 816–29.
Hoop, C., Lin, H.-K.; Kar, K.; Hou, Z., Poirier, M., Wetzel, R., and Van der Wel, P.C.A. Polyglutamine amyloid core boundaries and flanking domain dynamics in huntingtin fragment fibrils determined by solid-state NMR. Biochemistry 2014; 53: 6653–6666.
Mandal, A., Hoop, C.L., DeLucia, M., Kodali, R., Kagan, V., Ahn, J., and Van der Wel, P.C.A. Structural changes and pro-apoptotic peroxidase activity of cardiolipin-bound mitochondrial cytochrome c. Biophys J 2015; 109: 1873–1884
Hoop, C.L., Lin, H.-K., Kar, K., Magyarfalvi, G., Lamley, J.M., Boatz, J.C., Mandal, A., Lewandowski, J.R., Wetzel, R., and Van der Wel, P.C.A. Huntingtin exon 1 fibrils feature an interdigitated beta-hairpin-based polyglutamine core. Proc Natl Acad Sci USA. 2016; 113(6): 1546-51
Merg, A.D., Boatz, J.C., Mandal, A., Zhao, G., Mokashi-Punekar, S., Liu, C., Wang, X., Zhang, P., Van der Wel, P.C.A., and Rosi, N.L. Peptide-directed assembly of single-helical gold nanoparticle superstructures exhibiting intense chiroptical activity. J Am Chem Soc. 2016; 138(41):13655-13663.
Structural Polymorphism in the Misfolding and Aggregation of Expanded Polyglutamine Proteins
01/01/15 – 12/31/19
National Institutes of Health
The molecular basis of cardiolipin-protein interactions implicated in intrinsic apoptosis.
10/01/16 – 09/30/20
National Institutes of Health