Dr. Patrick C.A. van der Wel     Assistant professor     Department of Structural Biology     University of Pittsburgh School of Medicine     Biomedical Science Tower 3, room 2044     3501 Fifth Ave.     Pittsburgh, PA 15260     e-mail: pvdwel [AT] pitt.edu     phone: (412) 3839896

Research Interests 

Our interests are in the application of solid state NMR to allow structural studies on topics that are hard to address by other methods. Biological SSNMR is  a structural technique that allows accurate and direct measurements of structural and motional features of (partially) immobilized biomolecules.

Various human disorders involve the misfolding of proteins into fibrillar aggregates (including diseases like Huntington and Alzheimer's), and one of the research aims is to address the structure and formation of these amyloid fibril aggregates. Furthermore, in the cells many proteins are immobilized (in their functional and active state) by being associated with or embedded in the lipid bilayers that make up biological membranes. Such membrane-associated proteins are involved in a range of essential functions, such as membrane receptor proteins (common targets for pharmaceuticals). Our interests are in the interplay or interaction between the lipids in the membrane and the bound membrane proteins. Interestingly, this has been found to be a two-way process that can control and affect both the functioning of the proteins and the behavior of the membrane as a whole.

Addressing these topics will rely on a combination of various solid state NMR methodologies and complementary techniques. Some of the links to the left address features of these topics and highlight some of my previous work, using different experimental SNMR approaches. My  past research has involved structural measurements on microcrystalline and fibrillar polypeptide aggregates, as well as the study of protein-lipid interactions. (more current info coming soon!)

Selected Publications (see here for a complete listing)

• Targeted (13)C-(13)C Distance Measurements in a Microcrystalline Protein via J-Decoupled Rotational Resonance Width Measurements.
  Van der Wel, P.C.A.; Eddy, M.T.; Ramachandran, R., and Griffin, R.G. (2009) ChemPhysChem 10 (9-10): 1656-1663 DOI
• Observation of a low-temperature, dynamically driven structural transition in a polypeptide by solid state NMR spectroscopy
  Bajaj, V.S.; van der Wel, P.C.A., and Griffin, R.G. (2009) J. Am. Chem. Soc. in press  Online
• Solid state NMR study of amyloid nanocrystals and fibrils formed by the peptide GNNQQNY from yeast prion protein Sup35p.
  Van der Wel, P.C.A.; Lewandowski, J.R., and Griffin, R.G. (2007) J. Am. Chem. Soc. 129(16): 5117-5130 Online DOI
  
• Orientation and motion of tryptophan interfacial anchors in membrane-spanning peptides.
  Van der Wel, P.C.A.; Reed, N.D.; Greathouse, D.V., and Koeppe, R.E., II (2007) Biochemistry 46(25):7514-24  Abstract DOI 
  
•  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
  
• Multipole-multimode Floquet theory of rotational resonance width experiments: ¹³C-¹³C distance measurements in uniformly labeled solids.
  Ramachandran, R.; Lewandowski, J.R.; van der Wel, P.C.A., and Griffin, R.G. (2006) J. Chem. Phys. 124(21): 214107 Abstract
  
• Hydrophobic mismatch between helices and lipid bilayers.
  Weiss, T.M.; van der Wel, P.C.A.; Killian, J.A.; Koeppe, R.E., II, and Huang, H.W. (2003) Biophys J. 84: 379-385 Abstract
  
• Geometry and intrinsic tilt of a tryptophan anchored membrane spanning peptide by ²H NMR.
  Van der Wel, P.C.A.; Strandberg, E.; Killian, J.A., and Koeppe, R.E., II (2002) Biophys. J. 83(3): 1479-1488 Abstract Full Text  
  
• 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