Heinrich Roder, Ph.D.

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Adjunct Professor of Biochemistry and Biophysics
Department: Biochemistry and Biophysics
Graduate Group Affiliations

Contact information
Institute for Cancer Research
Fox Chase Cancer Center
333 Cottman Avenue
Philadelphia, PA 19111
Office: (215) 728-3123
Fax: (215) 728-3574
PhD (Biophysics)
Eidgenossiche Technische Hochschule (ETH) (Swiss Federal Institute of Technology), 1981.
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Description of Research Expertise

Research Interests:
We study mechanisms of protein folding and dynamic aspects of protein structure using NMR, optical spectroscopy, rapid kinetics and other biophysical approaches.

Protein folding, structure, dynamics, intrinsic disorder, ligand binding, NMR, hydrogen exchange, fluorescence, rapid kinetics.

Research Details:
To decipher the mechanism by which proteins acquire their precisely folded three dimensional structures remains one of the most important challenges of structural biology. We approach this complex problem by using optical and NMR methods for detailed structural, thermodynamic and kinetic studies on several small proteins with diverse structural characteristics. To monitor their folding or unfolding reactions, we rely on various optical probes coupled with rapid mixing techniques, including a new continuous-flow method with greatly improved time resolution (~50 microseconds). Hydrogen exchange and NMR methods provide insight into the structural and dynamic properties of kinetic intermediates and partially folded equilibrium states. By combining these biophysical approaches with site-specific mutagenesis, we can elucidate the role of individual residues in stabilizing the various conformational states that participate in folding.

We also rely on multidimensional NMR to investigate the structure, dynamics and molecular interactions of proteins involved in cell signaling and cancer. For example, we are interested in understanding the conformation, dynamics and functional role of two long intrinsically disordered regions in Na+/H+ exchanger regulatory factor (NHERF), a signaling adaptor protein comprising two PDZ domains and a C-terminal ezrin binding motif. Our NMR and thermodynamic data indicate that the activity of NHERF as a signaling adapter is regulated by a complex equilibrium between various open and closed (auto-inhibited) conformations.

Selected Publications

Chen, K. C., Xu, M., Wedemeyer, W. J., Roder, H.: Microsecond Unfolding Kinetics of Sheep Prion Protein Reveals an Intermediate that Correlates with Susceptibility to Classical Scrapie. Biophysical Journal 101(5): 1221-30, 2011.

Lau, W. L., Degrado, W. F., Roder, H.: The effects of pK(a) tuning on the thermodynamics and kinetics of folding: design of a solvent-shielded carboxylate pair at the a-position of a coiled-coil. Biophysical Journal 99(7): 2299-308, 2010.

Cheng, H., Li, J., Fazlieva, R., Dai, Z., Bu, Z., Roder, H.: Autoinhibitory Interactions between the PDZ2 and C-terminal Domains in the Scaffolding Protein NHERF1. Structure 17(5): 660-9, 2009.

Latypov, R. F., Maki, K., Cheng, H., Luck, S. D., Roder, H.: Folding mechanism of reduced Cytochrome c: equilibrium and kinetic properties in the presence of carbon monoxide. J. Mol. Biol. 383(2): 437-53, 2008.

Samuel, D., Cheng, H., Riley, P. W., Canutescu, A. A., Nagaswami, C., Weisel, J. W., Bu, Z., Walsh, P. N., Roder, H.: Solution structure of the A4 domain of factor XI sheds light on the mechanism of zymogen activation. Proc. Natl. Acad. Sci. U.S.A. 104(40): 15693-8, 2007.

Maki, K., Cheng, H., Dolgikh, D. A., Roder, H.: Folding kinetics of staphylococcal nuclease studied by tryptophan engineering and rapid mixing methods. J. Mol. Biol. 368(1): 244-55, 2007.

Roder, H., Maki, K., Cheng, H.: Early events in protein folding explored by rapid mixing methods. Chemical Reviews 106: 1836-1861, 2006.

Latypov, R.F., H. Cheng, N.A. Roder, J. Zhang and H. Roder: Structural characterization of an equilibrium unfolding intermediate in cytochrome c. J. Mol. Biol 357: 1009-1025, 2006.

Apetri, A. C., Maki, K., Roder, H., Surewicz, W. K.: Early intermediate in human prion protein folding as evidenced by ultrarapid mixing experiments. J. Amer. Chem. Soc. 128(35): 11673-8, 2006.

Welker, E., K. Maki, M.C. Shastry, D. Juminaga, R. Bhat, H.A. Scheraga, and H. Roder : Ultrarapid mixing experiments shed new light on the characteristics of the initial conformational ensemble during the folding of ribonuclease A. Proc. Natl. Acad. Sci. U.S.A. 101: 17681-17686, 2004.

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Last updated: 09/18/2014
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