Dorothee Kern
Degrees
Martin Luther University, Ph.D.Martin Luther University, M.S.
Martin Luther University, B.S.
Expertise
Protein structure, dynamic and evolution using experimental and computational methodsProfile
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Dorothee Kern is Professor of Biochemistry at Brandeis University and an Investigator of the Howard Hughes Medical Institute. She received her PhD at the Martin Luther University in Halle, Germany and then carried out her postdoctoral studies at UC Berkeley. She joined the faculty at Brandeis University in 1998.
Her research group studies the dynamical nature of proteins with the goal to reveal the interplay between structure, dynamics and function. She has been a major contributor in the experimental characterization of protein dynamics during enzyme catalysis and signaling. Her group is exploring the evolution of complex biological function as well as rational drug design by combining a variety of biophysical methods such as NMR, x-ray, fast kinetics, fluorescence, MD simulation, ancestral reconstruction and life-cell imaging.
Dr. Kern is the recipient of the Pfizer Award in Enzyme Chemistry from the American Chemical Society, the Dayhoff Award from the Biophysical Society, the Young Investigator Award of the International Association for Protein Structure Analysis and Proteomics, the Strage Award for Aspiring Young Science Faculty, was awarded the National Lecturer of the Biophysical Society, and is elected member of National Academy of Science of Germany Leopoldina. Before her professional scientific carrier, she was captain of the German National Basketball team for many years and won the MVP award of the German National league. Webpage
Courses Taught
| BCBP | 200b | Reading in Macromolecular Structure-Function Analysis |
| BCHM | 91g | Introduction to Research Practice |
| BCHM | 101a | Advanced Biochemistry: Enzyme Mechanisms |
| BIOL | 91g | Introduction to Research Practice |
Awards and Honors
Elected Member of the National Academy of Science of Germany Leopoldina (2017)
Robert Greenberg Lectureship Michigan University (2011)
Robert Ross Lectureship Ohio State University (2011)
Charles Slichter Lecture (2010)
Goodman Lecture (2009)
National Lecturer of the Biophysical Society (2009)
Howard Hughes Medical Institute Investigator (2005)
Dayhoff Award from the Biophysical Society (2004)
Alberta Gotthardt and Henry Strage Award for Aspiring Young Science Faculty (2003)
Pfizer Award in Enzyme Chemistry, American Chemical Society (2003)
Young Investigator Award of the International Association for Protein Structure Analysis (2002)
Dorothea Erxleben Prize (1995)
Martin Luther Medal (1995)
Postdoctoral Fellowship from German National Scholarship Foundation and BASF (through 1997) (1995)
Graduate fellowship from the German National Scholarship Foundation (through 1993) (1991)
Captain, 1st Division and National Basketball Teams of Germany (through 1991) (1984 - 1991)
Lessing Medal (1984)
Member, 1st Division and National Basketball Teams of Germany (through 1993) (1981 - 1992)
Scholarship
R. Otten, R. Pádua, H. A. Bunzel, V. Nguyen, W. Pitsawong, M. Patterson, S. Sui, S. L. Perry, A. E. Cohen, D. Hilvert, D. Kern. "How directed evolution reshapes energy landscapes in enzymes to boost catalysis." Science. vol. 370 1442-1446. Science, 2021.
A. Hadzipasic, C. Wilson, V. Nguyen, N. Kern, C. Kim, W. Pitsawong, J. Villali, Y. Zheng and D. Kern. "Ancient Origins of Allosteric Activation in a Ser-Thr Kinase." Science 21. 367 (2020)
Adelajda Zorba, Vy Nguyen, Akiko Koide, Yuejiao Zheng, Steffen Kutter, Shohei Koide and Dorothee Kern. "Allosteric modulation of a human protein kinase with monobodies." PNAS 116. 28 (2020)
J. B. Stiller, S. J. Kerns, M. Hoemberger, Y-J. Cho, R. Otten, M. F. Hagan and D. Kern. "Probing the Transition State in Enzyme Catalysis by High-Pressure NMR Dynamics." Nature Catalysis 2. 1 (2020)
Kern, Dorothee, R. Otten, L.Liu , L.R. Kenner, M. W. Clarkson, D. Mavor, D.S. Tawfik, and J. S. Fraser. "Rescue of Conformational Dynamics in Enzyme Catalysis by Directed Evolution." Nature Communications in press. (2018).
Kern, Dorothee, W. Pitsawong, V. Buosi, R. Otten, R. V. Agafonov, A. Zorba, N. Kern, S. Kutter, G. Kern, R. AP. Pádua, X. Meniche. "Dynamics of human protein kinases linked to drug selectivity." bioRxiv 286310; (2018)
V. Nguyen, C. Wilson, M. Hoemberger, J. Stiller, R. Agafonov, J. English, S. Kutter, D. Theobald and Kern, Dorothee. "Evolutionary Drivers of Thermoadaptation in Enzyme Catalysis”." Science (2017).
Agafonov R.V., Wilson C, Kern, Dorothee,. "Evolution and intelligent design in drug development.." Frontiers in Molecular Biosciences 2. (2016): 27.
Chakrabarti KS, Agafonov RV, Pontiggia F, Otten R, Higgins MK, Schertler GF, Oprian DD, Kern, Dorothee. "Conformational Selection in a Protein-Protein Interaction Revealed by Dynamic Pathway Analysis.." Cell Reports 14. 1 (2016): 32.
Eichner T, Kutter S, Labeikovsky W, Buosi V, Kern, Dorothee. "Molecular mechanism of Pin1-tau recognition and catalysis." J Mol Biol March 17. (2016).
F. Pontiggia, D.V.Pachov, M.W.Clarkson, J. Villali, M.F.Hagan, V.S.Pande, Kern, Dorothee,. "Free energy landscape of activation in a signaling protein at atomic resolution." Nature Commun 15. 6 (2016): 7284.
Kutter S, Eichner T, Deaconescu AM, Kern, Dorothee. "Regulation of microtubule assembly by tau and not by Pin1." J Mol BIOL March 17. (2016).
C. Wilson, R. V. Agafonov, M. Hoemberger, S. Kutter, A. Zorba, J. Halpin, V. Buosi, R. Otten, D. Waterman, D. L. Theobald and D. Kern. "Using Ancient Protein Kinases to Unravel a Modern Cancer Drug’s Mechanism." Science 347. 6224 (2015): 882-6.
Hass MA , Liu WM, Agafonov RV, Otten R, Phung LA, Schilder JT, Kern D, Ubbink M. "A minor conformation of a lanthanide tag on adenylate kinase characterized by paramagnetic relaxation dispersion NMR spectroscopy." J Biomol NMR 61. 2 (2015): 123-36.
S.J. Kerns, R.V. Agafonov, Y.-J. Cho, F. Pontiggia, R. Otten, D.V. Pachov, L.A. Phung, P.N. Murphy, V. Thai, M.F. Hagan, T. Alber, D. Kern. "Energy landscape of Adenylate Kinase Catalysis." Nature Struct Mol Biol 22. 2 (2015): 124-31.
A. Zorba, V. Buosi , S. Kutter , N. Kern , F. Pontiggia , Y.J. Cho and D.Kern. "Molecular mechanism of Aurora A kinase autophosphorylation and its allosteric activation by TPX2." Elife May 27;3:e02667.. (2014).
R.V. Agafonov, C. Wilson, R. Otten, V. Buosi, D. Kern. "Energetic dissection of Gleevec’s selectivity towards human tyrosine kinases." Nature Struct Mol Biol 10. (2014): 848-53.
Villali, J., Pontiggia, F., Clarkson, M.W., Hagan, M. and Kern, D.. "Evidence against the 'Y-T coupling' mechanism of activation in the response regulator NtrC." J Mol Biol 426. 7 (2014): 1554-67.
Park, J.M; Hu, J.H.; Milshteyn, A.; Zhang, P.-W.; Moore, C.G. ; Park, S.; Datko, M.C.; Doming, R.D.; Reye, C.M.; Wang, X.J.; Etzkorn, F.A.; Xiao, B.; Szumlinski, K.K.; Kern, D.; Linden, D.J.; Worley, P.F. "A Prolyl-isomerase Mediates Dopamine-dependent Plasticity and Cocaine Motor Sensitization." Cell 154. 3 (2013): 637-650.
Ranaghan MJ, Kumar RP, Chakrabarti KS, Buosi V, Kern D, Oprian DD.. "A Highly Conserved Cysteine of Neuronal Calcium-sensing Proteins Controls Cooperative Binding of Ca2+ to Recoverin." J Biol Chem 288. 50 (2013): 36160-7.
Morrison EA, DeKoster GT, Dutta S, Vafabakhsh R, Clarkson MW, Bahl A, Kern D, Ha T, Henzler-Wildman KA.. "Antiparallel EmrE exports drugs by exchanging between asymmetric structures.." Nature 481. (2011): 45-50.
Bosco DA, Eisenmesser EZ, Clarkson MW, Wolf-Watz M, Labeikovsky W, Millet O, Kern D.. "“Dissecting the Microscopic Steps of the Cyclophilin A Enzymatic Cycle on the Biological Substrate HIV Capsid by NMR.”." J. Mol. Biol. 403. 5 (2010): 723-738.
Otten R, Villali J, Kern D, Mulder FA.. "“Probing Microsecond Time Scale Dynamics in Proteins by Methyl (1)H Carr-Purcell-Meiboom-Gill Relaxation Dispersion NMR Measurements. Application to Activation of the Signaling Protein NtrC(r)”.." J Am Chem Soc. 132. 47 (2010): 17004-17014.
Villali, J. and Kern, Dorothee. "“Choreographing an enzyme's dance.”." Curr Opin Chem Biol. 5. 1 (2010): 636-643.
Clarkson MW, Lei M, Eisenmesser EZ, Labeikovsky W, Redfield A. and Kern, Dorothee. "Mesodynamics in the SARS nucleocapsid measured by NMR field cycling." J Biomol NMR 45. 1 (2009): 217-225.
Fraser, J.S., Clarkson, M.W., Degnan, S.C., Erion, R., Kern, D. Alber, T.. "Hidden alternative structures of proline isomerase essential for catalysis." Nature 462. 1 (2009): 669-673.
Gardino, A.K., Villali, J., Kivenson, A., Lei, M., Liu, C.F., Steindel, P. Eisenmesser, E.Z., Labeikovsky, W. Wolf-Watz, M., Clarkson. M.W. and Kern, Dorothee. "Transient non-native bonds promote activation of a signaling protein." Cell 139. 6 (2009): 1109-1118.
Lei, M., Velos, J., Gardino, A., Kivenson, A., Karplus, M. and Kern, Dorothee. "Segmented Transition Pathway of the Signaling Protein Nitrogen Regulatory Protein C." J. Mol. Biol. 392. 3 (2009): 823-836.
Shim S, Yuan JP, Kim JY, Zeng W, Huang G, Milshteyn A, Kern, Dorothee, Muallem S, Ming GL, Worley PF. "Peptidyl-prolyl isomerase FKBP52 controls chemotropic guidance of neuronal growth cones via regulation of TRPC1 channel opening." Neuron 64. 1 (2009): 471-483.
Gardino, A.K. and Kern D.. "¿Functional Dynamics of Response Regulators using NMR Relaxation Techniques¿." Methods in Enzym 423. (2008): :149-165..
Henzler-Wildman KA, Lei M, Thai V, Kerns SJ, Karplus M, Kern D.. "A hierarchy of timescales in protein dynamics is linked to enzyme catalysis." Nature 450. 7171 (2008): 913-916.
Henzler-Wildman KA, Thai V, Lei M, Ott M, Wolf-Watz M, Fenn T, Pozharski E, Wilson MA, Petsko GA, Karplus M, Hübner CG, Kern D. ".¿ Intrinsic motions along an enzymatic reaction trajectory.." Nature 450. 7171 (2008): 838-844.
Henzler-Wildman KA. and Kern D. "Dynamic personalities of proteins." Nature 450. 7172 (2008): 964-972.
Labeikovsky, W., Eisenmeser, E. Z. , Bosco, D.A. and Kern, Dorothee. "¿Structure and dynamics of Pin1 during catalysis by NMR¿." J. Mol. Biol. 367. 5 (2007): 1370-1381.
Thai V, Renesto P, Fowler CA, Brown D, Davis T, Gu W, Pollock DD, Kern D, Raoult D, Eisenmesser EZ. "Structural, Biochemical, and in Vivo Characterization of the First Virally Encoded Cyclophilin from the Mimivirus." J Mol Biol. Aug 29; [Epub ahead of print]. (2007).
Eisenmesser, E.Z., Millet, O., Labeikovsky, W., Korzhnev, D.M., Wolf-Watz, M., Bosco, D.A., Skalicky, J.J., Kay, L.E. and Kern, Dorothee. ""Intrinsic dynamics of an enzyme underlies catalysis"." Nature 438. (2005): 117-121.
Kern, Dorothee Eisenmesser, E.Z. & Wolf-Watz, M.. "Enzyme Dynamics During Catalysis Measured by NMR Spectroscopy." Meth. Enzymol (2005).
Tittmann, K., Neef, H., Golbik, R., Hübner, G. and Kern, Dorothee. "¿Kinetic control of thiamin diphosphate activation in enzymes studied by proton-nitrogen correlated NMR spectroscopy¿." Biochemistry 44. (2005): 8697-8700.
Wemmer, DE. and Kern, Dorothee. ""Beryllofluoride binding mimics phosphorylation of aspartate in response regulators"." J Bacteriol. 187. 24 (2005): 8229-8230.
Bosco, D.A. and Kern, D.. "Catalysis and Binding of Cyclophilin A with Different HIV-1 Capsid Constructs." Biochemistry (2004).
Kern, Dorothee Wolf-Watz, M. Thai, V. Henzler-Wildman, K. Hadjipavlou, G. & Eisenmesser, E.Z.. "Linkage Between Dynamics and Catalysis in a Thermophilic - Mesophilic Enzyme Pair." Nat. Struct. Mol. Biol. (2004).
Gardino, A.K. Volkman, B.F. Cho, H.S. Lee, S.Y. Wemmer, D.E. & Kern, D.. "The NMR Solution Structure of BeF3-Activated Spo0F Reveals the ConformationalSwitch in a Phosphorelay System." J. Mol. Biol. (2003).
Kern, D. and Zuiderweg, E.R.P.. "The Role of Dynamics in Allosteric Regulation." Current Opinion in Structural Biology (2003).