Professor of Biochemistry
HHMI Investigator
Volen 444
Department of Biochemistry, MS 009
Brandeis University
415 South Street
Waltham, MA 02453-2728
tel: 781 736 2354
dkern (at) brandeis.edu
Education
- 1988 - BSc Biochemistry, Martin-Luther University of Halle, Germany
- 1989 - MSc Biochemistry, Martin-Luther University of Halle, Germany
- 1994 - PhD Biochemistry, Martin-Luther University of Halle, Germany
- 1998 - Postdoc Structural Biology, Dept. of Chemistry, University of California, Berkeley & Structural Biology Division, Lawrence Berkeley National Laboratory
Motions are the basis for the function of biological macromolecules. Whereas for many enzymes the structures have been solved, very little is known about dynamic processes, which trigger catalysis. Our main goal is to characterize these motions in enzymes to provide a better understanding of the atomic events in enzyme catalysis as a function of time. We use NMR as a primary tool because it is an excellent method to measure dynamic processes ranging from picoseconds to days. We complement our experiments by computational techniques, namely, molecular dynamics simulations, which provide atomistic insight into the dynamics of macromolecules. Our aim is to reveal the physical mechanism of transitions by combining experimental to computational methods. Click here for more details about our current research and/or read our published work.
Postdoctoral Fellow
Joined the lab in: 2011
Volen 443
Department of Biochemistry, MS 009
Brandeis University
415 South Street
Waltham, MA 02453-2728
tel: 781 736 2326
ottenr (at) brandeis.edu
Education
- 2006 - MSc Chemistry, Department of Biophysical Chemistry, University of Groningen, Groningen, The Netherlands
- 2011 - PhD Chemistry, Department of Biophysical Chemistry, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Groningen, The Netherlands
Over the past decade(s) it has been become increasingly evident that both a high-resolution structure and a detailed insight in its dynamics are of critical importance to understand the function of a biological macromolecule. Nuclear magnetic resonance (NMR) spectroscopy is one of the most powerful techniques to study protein dynamics over a wide range of time scales and, moreover, can provide such information for many different nuclei with atomic resolution. I am interested in the development and application of NMR methodology to study protein structure/dynamics, with the goal to elucidate the intricate relationship between protein structure/dynamics and enzyme catalysis.
Publications
From the Kern Lab:
Stiller JB#, Kerns SJ#, Hoemberger M, Cho Y-J, Otten R, Hagan MF & Kern D. Probing the Transition State in Enzyme Catalysis by High-Pressure NMR Dynamics. Nat. Catal. 2019
Pádua RAP#, Sun Y#, Marko I, Pitsawong W, Stiller JB, Otten R & Kern D. Mechanism of Activating Mutations and Allosteric Drug Inhibition of the Phosphatase SHP2. Nat. Commun. 2018
Pitsawong W#, Buosi V#, Otten R#, Agafonov RV#, Zorba A, Kern N, Kutter S, Kern G, Pádua RAP, Meniche X & Kern D. Dynamics of Human Protein Kinase Aurora A Linked to Drug Selectivity. eLife 2018
Otten R#, Liu L#, Kenner LR, Clarkson MW, Mavor D, Tawfik DS, Kern D & Fraser JS. Rescue of Conformational Dynamics in Enzyme Catalysis by Directed Evolution. Nat. Commun. 2018
Chakrabarti KS#, Agafonov RV#, Pontiggia F, Otten R, Higgins MK, Schertler GF, Oprian DD & Kern D. Conformational Selection in a Protein-Protein Interaction Revealed by Dynamic Pathway Analysis. Cell Reports 2016
Wilson C#, Agafonov RV#, Hoemberger M, Kutter S, Zorba A, Halpin J, Buosi V, Otten R, Waterman D, Theobald DL & Kern D. Using ancient protein kinases to unravel a modern cancer drug’s mechanism. Science 2015
Kerns SJ#, Agafonov RV#, Cho YJ#, Pontiggia F, Otten R, Pachov DV, Kutter S, Phung LA, Murphy PN, Thai V, Alber T, Hagan MF & Kern D. The energy landscape of adenylate kinase during catalysis. Nat. Struct. Mol. Biol. 2015
Hass MA, Liu WM, Agafonov R.V., 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. 2015
Agafonov RV#, Wilson C#, Otten R, Buosi V & Kern D. Energetic dissection of Gleevec’s selectivity toward human tyrosine kinases. Nat. Struct. Mol. Biol. 2014
Other:
Niklasson M, Otten R, Ahlner A, Andresen C, Schlagnitweit J, Petzhold K & Lundström P. Comprehensive Analysis of NMR Data Using Advanced Line Shape Fitting. J. Biomol. NMR 2017
Oktaviani NA, Risor MW, Lee YH, Megens RP, de Jong DH, Otten R, Scheek RM, Enghild JJ, Nielsen NC, Ikegami T & Mulder FAA. Optimized Co-Solute Paramagnetic Relaxation Enhancement for the Rapid NMR Analysis of a Highly Fibrillogenic Peptide. J. Biomol. NMR 2015
Maeno SJ, Sindhikara D, Hirata F, Otten R, Dahlquist FW, Yokoyama S, Akasaka K, Mulder FAA & Kitahara R. Cavity as a Source of Conformational Fluctuation and High-Energy State: High-Pressure NMR Study of a Cavity-Enlarged Mutant of T4 Lysozyme. Biophys. J. 2015
Chu BCH, Otten R, Krewulak KD, Mulder FAA & Vogel HJ. The Solution Structure, Binding Properties, and Dynamics of the Bacterial Siderophore-Binding Protein FepB. J. Biol. Chem. 2014
Meniche X, Otten R, Siegrist MS, Baer CE, Murphy KC, Bertozzi CR & Sassetti CM. Subpolar Addition of New Cell Wall Is Directed by DivIVA in Mycobacteria. Proc Natl. Acad. Sci. USA 2014
Wood K#, Gallat FX#, Otten R#, van Heel AJ, Lethier M, van Eijck L, Moulin M, Haertlein M, Weik M & Mulder FAA. Protein Surface and Core Dynamics Show Concerted Hydration-Dependent Activation. Angew. Chem. Int. Ed. 2013
Stockbridge RB, Lim HH, Otten R, Williams C, Shane T, Weinberg Z & Miller C. Fluoride Resistance and Transport by Riboswitch-Controlled CLC Antiporters. Proc Natl. Acad. Sci. USA 2012
Wood K, Paz A, Dijkstra K, Scheek RM, Otten R, Silman I, Sussman JL & Mulder FAA. Backbone and Side Chain NMR Assignments for the Intrinsically Disordered Cytoplasmic Domain of Human neuroligin-3. Biomol. NMR Assign. 2012
Karasawa A, Erkens GB, Berntsson RPA, Otten R, Schuurman-Wolters GK, Mulder FAA & Poolman B. Cystathionine β-Synthase (CBS) Domains 1 and 2 Fulfill Different Roles in Ionic Strength Sensing of the ATP-binding Cassette (ABC) Transporter OpuA. J. Biol. Chem. 2011
Mulder FAA, Otten R & Scheek RM. Origin and Removal of Mixed-Phase Artifacts in Gradient Sensitivity Enhanced Heteronuclear Single Quantum Correlation Apectra. J. Biomol. NMR 2011
Meinema AC#, Laba JK#, Hapsari RA#, Otten R, Mulder FAA, Kralt A, van den Bogaart G, Lusk CP, Poolman B & Veenhoff LM. Long Unfolded Linkers Facilitate Membrane Protein Import Through the Nuclear Pore Complex. Science 2011
Wood K, Paz A, Dijkstra K, Scheek RM, Otten R, Silman I, Sussman JL & Mulder FAA. Backbone and Side Chain NMR Assignments for the Intrinsically Disordered Cytoplasmic Domain of Human neuroligin-3. Biomol. NMR Assign. 2011
Oktaviani NA, Otten R, Dijkstra K, Scheek RM, Thulin E, Akke M & Mulder FAA. 100% Complete Assignment of Non-Labile 1H, 13C, and 15N Signals for Calcium-Loaded Calbindin D9k P43G Biomol. NMR Assign. 2011
Otten R, Villali J, Kern D & Mulder FAA. Probing Microsecond Time Scale Dynamics in Proteins by Methyl 1H Carr−Purcell−Meiboom−Gill Relaxation Dispersion NMR Measurements. Application to Activation of the Signaling Protein NtrCr. J. Am. Chem. Soc. 2010
Otten R, Chu B, Krewulak KD, Vogel HJ & Mulder FAA. Comprehensive and Cost-Effective NMR Spectroscopy of Methyl Groups in Large Proteins J. Am. Chem. Soc. 2010
Otten R#, Wood K# & Mulder FAA. Comprehensive Determination of 3JHNHα for Unfolded Proteins Using 13C′-Resolved Spin-Echo Difference Spectroscopy. J. Biomol. NMR 2009
Louhivuori M, Otten R, Salminen T & Annila A. Evidence of Molecular Alignment Fluctuations in Aqueous Dilute Liquid Crystalline Media. J. Biomol. NMR 2007
Louhivuori M, Otten R, Lindorff-Larsen K & Annila A. Conformational Fluctuations Affect Protein Alignment in Dilute Liquid Crystal Media. J. Am. Chem. Soc. 2006
Otten R, van Lune FS, Dijkstra K & Scheek RM. Letter to the Editor: 1H, 13C, and 15N Resonance Assignments of the Phosphorylated Enzyme IIB of the Mannitol-Specific Phophoenolpyruvate-Dependent Phosphotransferase System of Escherichia coli. J. Biomol. NMR 2004
Postdoctoral Fellow
Joined the lab in: 2015
Volen 443
Department of Biochemistry, MS 009
Brandeis University
415 South Street
Waltham, MA 02453-2728
tel: 781 736 2326
warintra (at) brandeis.edu
Education
- 2007 - BSc Chemistry, Mahidol University, Bangkok, Thailand
- 2009 - MSc Biochemistry, Mahidol University, Bangkok, Thailand
- 2014 - PhD Chemistry, University of Kentucky, Lexington, KY, USA
Publications
From the Kern Lab:
Hadzipasic A, Wilson C, Nguyen V, Kern N, Kim C, Pitsawong W, Villali J, Zheng Y & Kern D. Ancient origins of allosteric activation in a Ser-Thr kinase Science 2020
Pádua RAP#, Sun Y#, Marko I, Pitsawong W, Stiller JB, Otten R & Kern D. Mechanism of Activating Mutations and Allosteric Drug Inhibition of the Phosphatase SHP2. Nat. Commun. 2018
Pitsawong W#, Buosi V#, Otten R#, Agafonov RV#, Zorba A, Kern N, Kutter S, Kern G, Pádua RAP, Meniche X & Kern D. Dynamics of Human Protein Kinase Aurora A Linked to Drug Selectivity. eLife 2018
Other:
Pitsawong W, Chenprakhon P, Dhammaraj T, Medhanavyn D, Sucharitakul J, Tonsook C, van Berkel WJH, Chaiyen P & Miller A-F. Tuning of pKas activates substrates in flavin-dependent aromatic hydroxylases. J. Biol. Chem. 2020
Miller A-F, Park JT, Ferguson KL, Pitsawong W & Bommarius AS. Informing Efforts to Develop Nitroreductase for Amine Production. Molecules 2018
Pitsawong W, Haynes CA, Koder RL, Rodgers DW & Miller A-F. Mechanism-Informed Refinement Reveals Altered Substrate-Binding Mode for Catalytically Competent Nitroreductase. Structure 2017
Pitsawong W, Hoben JP & Miller A-F. Understanding and Exploiting the Broad Substrate Repertoire of Nitroreductase via Kinetic Mechanism. J. Biol. Chem. 2014
Tinikul R#, Pitsawong W#, Sucharitakul J, Nijvipakul S, Ballou DP & Chaiyen P. The Transfer of Reduced Flavin Mononucleotide from LuxG Oxidoreductase to Luciferase Occurs via Free Diffusion. Biochemistry 2013
Tan T-C, Pitsawong W, Wongnate T, Spadiut O, Haltrich D, Chaiyen P & Divne C. H-bonding and Positive Charge at the N(5)/O(4) Locus Are Critical for Covalent Flavin Attachment in Trametes Pyranose 2-Oxidase. J. Mol. Biol. 2010
Pitsawong W, Sucharitakul J, Prongjit M, Tan T-C, Spadiut O, Haltrich D, Divne C, & Chaiyen P. A Conserved Active-site Threonine Is Important for Both Sugar and Flavin Oxidation of Pyranose 2-Oxidase. J. Biol. Chem. 2010
Postdoctoral Fellow
Joined the lab in: 2015
Volen 443
Department of Biochemistry, MS 009
Brandeis University
415 South Street
Waltham, MA 02453-2728
tel: 781 736 2326
rpadua (at) brandeis.edu
Education
- 2008 - BSc Pharmacy and Biochemistry, Universidade de São Paulo, Ribeirão Preto, Brazil
- 2014 - PhD in Sciences, Faculdade de Ciências Farmacêuticas de Ribeirão Preto Universidade de São Paulo (Brazil) and Queen Mary - University of London (England)
- 2015 - Postdoctoral Fellow at Laboratory of Protein Crystallography of Ribeirão Preto - FCFRP-USP, Brazil
Publications
From the Kern Lab:
Pádua RAP#, Sun Y#, Marko I, Pitsawong W, Stiller JB, Otten R & Kern D. Mechanism of Activating Mutations and Allosteric Drug Inhibition of the Phosphatase SHP2. Nat. Commun. 2018
Pitsawong W#, Buosi V#, Otten R#, Agafonov RV#, Zorba A, Kern N, Kutter S, Kern G, Pádua RAP, Meniche X & Kern D. Dynamics of Human Protein Kinase Aurora A Linked to Drug Selectivity. eLife 2018
Other:
Sartim MA, Pinheiro MP, Pádua RAP, Sampaio SV & Nonato MC. Structural and Binding Studies of a C-type Galactose-Binding Lectin from Bothrops jararacussu Snake Venom. Toxicon. 2017
Pádua RAP, Kia AM, Costa-Filho AJ, Wilkinson SR & Nonato MC. Characterisation of the Fumarate Hydratase Repertoire in Trypanosoma cruzi. Int. J. Biol. Macromol. 2017
Pádua RAP, Tomaleri GP, Reis RAG, David JS, Silva V, Pinheiro MP & Nonato MC. ThermoFMN - a Thermofluor Assay Developed for Ligand-Screening as an Alternative Strategy for Drug Discovery. J. Braz. Chem. Soc. 2014
Pádua RAP & Nonato MC. Cloning, Expression, Purification, Crystallization and Preliminary X-ray Diffraction Analysis of Recombinant Human Fumarase. Acta Crystallogr. F. Struct. Biol. Commun. 2014
Postdoctoral Fellow
Joined the lab in: 2020
Volen 443
Department of Biochemistry, MS 009
Brandeis University
415 South Street
Waltham, MA 02453-2728
tel: 781 736 2326
hannesludewig (at) brandeis.edu
Education
- 2012 - B.Sc. Biochemistry, University of Bayreuth, Germany
- 2014 - M.Sc. Biochemistry & Molecular Biology, University of Bayreuth, Germany
- 2020 - Ph.D. Chemistry, Centre for Doctoral Training in Critical Resource Catalysis, School of Chemistry, University of St Andrews, United Kingdom (Scotland)
Publications
Gkotsi DS, Ludewig H, Sharma SV, Connolly JA, Dhaliwal J, Wang Y, Unsworth WP, Taylor RJK, McLachlan MWM, Shanahan S, Naismith JH & Goss RJM. A marine viral halogenase that iodinates divers substrates. Nat. Chem. 2019
Ludewig H, Czekster CM, Oueis E, Munday ES, Arshad M, Synowsky SA, Bent AF & Naismith JH. Characterization of the Fast and Promiscuous Macrocyclase from Plant PCY1 Enables the Use of Simple Substrates. ACS Chem. Biol. 2018
Czekster CM, Ludewig H, McMahon SA & Naismith JH. Characterization of a dual function macrocyclase enables design and use of efficient macrocyclization substrates. Nat. Commun. 2017
Oueis E, Adamson C, Mann G, Ludewig H, Redpath P, Migaud M, Westwood NJ & Naismith JH. Derivatisable Cyanobactin Analogues: A Semisynthetic Approach. ChemBioChem 2015
Koehnke J, Mann G, Bent AF, Ludewig H, Shirran S, Botting C, Lebl T, Houssen WE, Jaspars M & Naismith JH. Structural analysis of leader peptide binding enables leader-free cyanobactin processing. Nat. Chem. Biol. 2015
Graduate Student
Joined the lab in: 2015
Volen 443
Department of Biochemistry, MS 009
Brandeis University
415 South Street
Waltham, MA 02453-2728
tel: 781 736 2326
pfinneran (at) brandeis.edu
Education
- 2014 - BA Chemistry / Biochemistry, Western Connecticut State University, Danbury, CT, USA
Thirty-two non-receptor tyrosine kinases have been identified in humans. All of these kinases had evolved from the same common ancestor at one point in time. These proteins are similar by their function (kinase activity), but they differ in the mechanism in which they are regulated, and in their substrate specificity. I am interested in researching the mechanism of how a kinase is able to recognize its target protein. By using ancestral sequence reconstruction (ASR) it may be possible to map what evolutionary changes in the protein led to a difference in its specificity. I also research how regulatory abilities evolved over time using similar techniques.
Graduate Student
Joined the lab in: 2015
Volen 443
Department of Biochemistry, MS 009
Brandeis University
415 South Street
Waltham, MA 02453-2728
tel: 781 736 2326
jstiller (at) brandeis.edu
Education
- 2014 - BSc Biochemistry, Trinity College, Hartford, CT, USA
Protein’s exist upon a delicate energy landscape where multiple states are within several kJ of one another. While current structural techniques characterize the lowest energy conformation, the higher energy states remain obscured. However, recently NMR techniques have been developed which allows one to infer structural information about these excited states. With that in mind, my interests involve structurally investigating protein ensembles and discovering how regulation and drug binding are manipulated by conformational interexchange.
Publications
From the Kern Lab:
Stiller JB#, Kerns SJ#, Hoemberger M, Cho Y-J, Otten R, Hagan MF & Kern D. Probing the Transition State in Enzyme Catalysis by High-Pressure NMR Dynamics. Nat. Catal. 2019
Pádua RAP#, Sun Y#, Marko I, Pitsawong W, Stiller JB, Otten R & Kern D. Mechanism of Activating Mutations and Allosteric Drug Inhibition of the Phosphatase SHP2. Nat. Commun. 2018
Nguyen V#, Wilson C#, Hoemberger M, Stiller JB, Agafonov RV, Kutter S, English J, Theobald D & Kern D. Evolutionary Drivers of Thermoadaptation in Enzyme Catalysis. Science 2017
Graduate Student
Joined the lab in: 2017
Volen 443
Department of Biochemistry, MS 009
Brandeis University
415 South Street
Waltham, MA 02453-2728
tel: 781 736 2326
bannista (at) brandeis.edu
Education
- 2016 - BSc Biochemistry BA French and Francophone Studies, Union College, Schenectady, NY, USA
Proteins are highly dynamic macromolecules that adopt various high-energy conformational states in solution to perform catalysis. These states are often fleeting and exist at low concentrations, which is why they are often thought of as subpopulations of a protein. Although X-ray crystallography has made recent advances in observing subpopulations, nuclear magnetic resonance (NMR) spectroscopy remains the most powerful instrument to understand the dynamic processes involved in the interconversion between major and minor conformational states. Therefore, my research interests lie in using NMR spectroscopy, to detect these subpopulations and understand how they contribute to protein regulation and catalysis.
Publications
Kretschmer PM, Bannister AM, MacManus-Spencer LA & Paulick MG. A Liquid Chromatography Tandem Mass Spectrometry Assay for the Detection and Quantification of Trehalose in Biological Samples. J. Chromatogr. B. 2016
Graduate Student
Joined the lab in: 2017
Volen 443
Department of Biochemistry, MS 009
Brandeis University
415 South Street
Waltham, MA 02453-2728
tel: 781 736 2326
kva0987 (at) brandeis.edu
Education
- 2016 - BSc Biochemistry, Texas A&M University, College Station, TX, USA
Publications
From the Kern Lab:
Hadzipasic A, Wilson C, Nguyen V, Kern N, Kim C, Pitsawong W, Villali J, Zheng Y & Kern D. Ancient origins of allosteric activation in a Ser-Thr kinase Science 2020
Zorba A#, Nguyen V#, Koide A, Hoemberger M, Zheng Y, Kutter S, Kim C, Koide S & Kern D. Allosteric Modulation of a Human Protein Kinase with Monobodies. Proc. Natl. Acad. Sci. USA 2019
Graduate Student
Joined the lab in: 2017
Volen 443
Department of Biochemistry, MS 009
Brandeis University
415 South Street
Waltham, MA 02453-2728
tel: 781 736 2326
imarko (at) brandeis.edu
Education
- 2016 - BSc Biochemistry, Worcester Polytechnic Institute, Worcester, MA, USA
Publications
From the Kern Lab:
Pádua RAP#, Sun Y#, Marko I, Pitsawong W, Stiller JB, Otten R & Kern D. Mechanism of Activating Mutations and Allosteric Drug Inhibition of the Phosphatase SHP2. Nat. Commun. 2018
Graduate Student
Joined the lab in: 2019
Volen 443
Department of Biochemistry, MS 009
Brandeis University
415 South Street
Waltham, MA 02453-2728
tel: 781 736 2326
andrewglaser (at) brandeis.edu
Education
- 2016 - BSc Biochemistry, Union College, Schenectady, NY, USA
Graduate Student
Joined the lab in: 2019
Volen 443
Department of Biochemistry, MS 009
Brandeis University
415 South Street
Waltham, MA 02453-2728
tel: 781 736 2326
mpatterson (at) brandeis.edu
Education
- 2018 - BSc Biochemistry, University of Massachusetts Boston, Boston, MA, USA
Adenylate kinase (ADK) is a phosphotransferase that regulates energy homeostasis by controlling intracellular nucleotide levels. ADK is an essential enzyme that is found across all domains of life, and its stability is correlated to organismal growth. This stability/fitness relationship imposes that ancestral ADK evolved modern sequences that are stable in the same environments occupied by their native organisms. I am interested in studying how ADK evolved by investigating the effects of mutations on the structural and dynamic properties of the enzyme using biophysical techniques such as X-ray crystallography and NMR spectroscopy.
Master Student
Joined the lab in: 2019
Volen 443
Department of Biochemistry, MS 009
Brandeis University
415 South Street
Waltham, MA 02453-2728
tel: 781 736 2326
chenl (at) brandeis.edu
Education
- 2018 - BSc Biochemistry, Zhejiang University, China
Undergraduate Student
Joined the lab in: 2018
Volen 443
Department of Biochemistry, MS 009
Brandeis University
415 South Street
Waltham, MA 02453-2728
tel: 781 736 2326
khollander (at) brandeis.edu
Undergraduate Student
Joined the lab in: 2018
Volen 443
Department of Biochemistry, MS 009
Brandeis University
415 South Street
Waltham, MA 02453-2728
tel: 781 736 2326
jirvin (at) brandeis.edu