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Wolfgang Peti, Ph.D., University of Frankfurt Germany, 2001

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Title: Associate Professor of Medical Science
Department: Molecular Pharmacology, Physiology & Biotechnology

Wolfgang_Peti@brown.edu
+1 401 863 6084, +1 401 863 6109

 
Overview | Research | Grants/Awards | Teaching | Publications

The focus of my research group is to understand the molecular mechanisms that regulates signalling enzymes. We combine the information derived from biomolecular NMR spectroscopy, X-ray crystallography, and additional biophysical techniques, such as ITC, DSC, Biacore, and CD spectroscopy. Enzymes of key interests are ser/thr protein phosphatases (PP1, PP2B), tyr phosphatases and ser/thr kinases, especially MAP Kinases. Furthermore, my research group is pursuing an molecular understanding for the formation of bacterial biofilms.

Biography

1992 – 1998 Diploma Magister rer. nat, Chemistry, summa cum laude, University of Vienna, Austria (Advisor Dr.Dr. B.K. Keppler)

1998 – 2001 Ph.D., Chemistry, summa cum laude, J.-W.-G. University Frankfurt, Germany (Advisor Dr. C. Griesinger)

2001 – 8/2004 Research Associate, The Scripps Research Institute, USA (Advisor Dr. K. Wüthrich)

9/2004 – 6/2010 Assistant Professor, MPPB, Brown University, USA

7/2006 – 8/2010 MPP Graduate Program Director, Brown University, USA

7/2007 – 6/2010 Manning Assistant Professor, MPPB, Brown University, USA

7/2008 – 6/2010 Assistant Professor of Chemistry, Brown University, USA

7/2010 – present Associate Professor (tenure) of Medical Science, Brown University, USA
7/2010 – present Associate Professor (tenure) of Chemistry, Brown University, USA
7/2012 – present Director Structural Biology Core Facility, Brown University, USA

Institutions

BU

Research Description

Signaling cascades direct information and, in turn, function from memory to muscle movement important at any stage of life. These cascades are mediated by a network of highly specific, tightly regulated series of protein:protein interactions, including those made by Serine/Threonine kinases and Serine/Threonine phosphatases. Our long-term goal is to achieve an in-depth understanding of this signaling network in the post synaptic density so we will be able to develop highly specific drugs for diseases such as Down's syndrome and mental retardation. Therefore we have started to investigate the role of the Serine/Threonine phosphatase Protein Phosphatase 1 (PP1) in neuronal signaling, as it is one of the most important protein phosphatases in the brain. Two of the major interaction partners of PP1 in neurons are the large, multi-domain scaffolding proteins Spinophilin and Neurabin. These proteins target PP1 to its cellular point of action, the post synaptic density of dendritic spines. This targeting of PP1 by Spinophilin and Neurabin is responsible for the PP1-mediated regulation of glutamatergic AMPA/NMDA channel activity. To understand the Spinophilin/PP1 and Neurabin/PP1 signaling networks in molecular detail, we will use NMR spectroscopy to elucidate the scaffolding properties of the Spinophilin and Neurabin protein interaction domains, both as isolated domains and in complex with their interaction peptides and binding proteins. Spinophilin and Neurabin also bind and organize actin. It has been shown that this organization is of key importance for dendritic synapses shape and therefore for early childhood learning, development, and memory. Therefore, these 3-dimensional structures, interaction maps, and biochemical studies will provide a detailed understanding of this specificity and will allow us to selectively modulate particular signaling cascades for medical benefit.

Awards

2007 - 2010 Manning Assistant Professor of Medical Science
2005 Rhode Island Foundation Medical Research Grant
2005 Richard B. Salomon Faculty Research Award
2004 Max-Kade Foundation Fellowship Award
2002 Ernst Award 2002 of the German Chemical Society
2002–2004 Erwin-Schrödinger-Stipend (FWF/Austria)
2001 European Union Research Training Network "Cross-Correlation" Young Investigator HPRN-CT-2000-00092
1998–2001 Member of the University Sponsor group of the Bayer AG
1998–2001 Kekulé thesis scholarship from the Scholarship Fund of the Association of the Chemical Industry in Germany
1996–1998 Performance scholarship of the Ministry for Science and Culture in Austria

Affiliations

1998 – 2005 GDCh member
2004 – Present ACS member
2006 – Present ASPET member
2007 – Present Protein Society member
2010 – Present ASBMB member

Funded Research

3R01-NS056128 (PI: Peti, W.) 10/01/07-06/30/13
NIH - NINDS
Structural and Functional Analysis of Signaling Proteins in Dendritic Spines

1R01GM098482-01 (MPI: Page, R., Peti, W.) 09/01/11-08/31/16
NIH - NIGMS
PP1 regulation in the nucleus

Teaching Experience

BI0019 S10: Proteins (Biology Foundations Courses)
Fall 2005; Fall 2006;

Freshmen Seminar Course: Students beginning in college-level biology are encouraged to choose a section of BI 19, courses that introduce biological sciences within the framework of particular topics. All BI 19 courses carry concentration credit in biology programs. In order to assure student/faculty interaction, these sections are limited in size. BI 19 courses are often suitable for students entering with AP biology credit. Some of these courses are designated as First Year Seminars.
Proteins are the expression of information in our genes. They help metabolize the food we eat, transport the air we breath, build our bodies, and color our eyes. To do so, they adopt a myriad of structural motifs. We examine the structural features of proteins and their functional consequences, as well as methods to experimentally determine or theoretically predict protein structure.
This course has been completely reorganized with a focus on modern techniques and approaches to protein structure analysis and a discussion of the structures of recently elucidated proteins and protein complexes, such as the ribosome.

BI0294 S1: Modern Topics in Structural Biology
Spring 2006;

An introduction into the modern approaches for structural biology; special focus was given to NMR spectroscopy methodology including recently introduced hardware, software and theoretical approaches. Examples for techniques were discussed using selected structures recently solved using NMR Spectroscopy. This was a completely new course at Brown University. The class was offered in a highly interactive arrangement including demonstrations at the NMR spectrometer.

BI0195.7 Selected Topics in Molecular Biophysics (Instructor: J. X. Tang)
Spring 2005, Spring 2006, Spring 2007
Contribution for biomolecular NMR spectroscopy

BI1940T Synthetic Biological Systems (Instructor: G. Wessel)
Fall 2007, Fall 2008
Contribution to Protein Engineering

BI2170 Receptors, Channels and Signaling (Molecular Pharmacology & Physiology Core Course)
Fall 2007, Fall 2008
Contribution Structure Based Drug Design

BI0110 Cell Physiology and Biophysics (Instructor: J. Kauer)
Spring 2007
Contribution to Protein Structure and biomolecular NMR spectroscopy

BI0201 A Introduction to MCB Faculty Trainer Research
Fall 2005, Fall 2006, Fall 2007, Fall 2008

BI0L1200 Protein Biophysics and Structural Biology
Spring 2008;

For the first time an upper-level under-graduate class for Protein Biophysics and Structural Biology is offered at Brown University, filling an essential educational gap. This is focusing on protein expression and purification, synthetic biology, chemical biology, introduction into biophysical techniques and an in-depth introduction into structural biology. This medium class size allows for much discussion and even student presentations.

BIOL1270 Advanced Biochemistry (Instructor: R. Page)
Fall 2008
Contribution to Protein Folding and Stability

BIOL1090 Polymer Science for Biomaterials (Instructor: E. Mathiowitz)
Fall 2008
Contribution to NMR Spectroscopy for Biopolymers

Courses Taught

  • Protein Biophysics and Structural Biology (BI0L1200)
  • S10 Biology Foundations Course Proteins: Primary Molecules of Life (BI0019)
  • S10 Modern Topics in Structural Biology (BI0294)

Selected Publications

  • Schüler, H. & Peti, W. (2008). Structure-Function Analysis of the F-actin Binding Domain of the Neuronal Scaffolding Protein Spinophilin, FEBS J., 275, 59-68.(2008)
  • Dancheck, B., Nairn, A.C. & Peti, W. (2008) Detailed Structural Characterization of Unbound Protein Phosphatase 1 Inhibitors, Biochemistry, 47, in press.(2008)
  • Critton, D.A., Tortajada, A., Stetson, G., Peti, W. & Page, R. (2008) Structural basis of substrate recognition by Hematopoietic Tyrosine Phosphatase (HePTP), Biochemistry, 47, in press.(2008)
  • Kelker, M.S., Page, R. & Peti, W. (2008) Crystal Structures of Protein Phosphatase-1 Bound to Nodularin-R and Tautomycin: A Novel Scaffold for Structure Based Drug Design of Serine/Threonine Phosphatase Inhibitors, J Mol Biol, in press.(2008)
  • Peti, W. & Page, R. (2007). Strategies to Maximize Heterologous Protein Expression in E. coli with Minimal Cost. Prot Exp Purif 57, 1-10.(2007)
  • Kelker, M. S., Dancheck, B., Ju, T., Kessler, R., Nairn, A. C. & Peti, W. (2007). Structural basis for Spinophilin and Neurabin receptor interaction. Biochemistry, 46, 2333-2344.(2007)
  • u, T., Ragusa, M. J., Hudak, J., Nairn, A. C. & Peti, W. (2007). Structural characterization of the neurabin SAM domain. Proteins,69(1), 192-198.(2007)
  • Placzek W.J., Etezady-Esfarjani T., Herrmann T., Pedrini B., Peti W., Alimenti C., Luporini P. & Wüthrich K. (2007) Cold-adapted signal proteins: NMR structures of pheromones from the antarctic ciliate Euplotes nobilii. IUBMB Life, 59(8), 578-585.(2007)
  • Lee, J, Page, R., García-Contreras, R., Palermino, J.M., Zhang, X.S., Doshi, O., Wood, T.K. & Peti, W. (2007) Structure and Function of the E. coli Protein YmgB: a Protein Critical for Biofilm Formation and Acid Resistance, J Mol Biol, 373(1), 11-26.(2007)
  • u, T. & Peti, W. (2007) Backbone and side chain 1H, 15N and 13C assignments of the human G-actin binding protein profilin II, Biomol. NMR Assign., 1, 205-207.(2007)
  • opson, R. & Peti, W. (2007) Micro-Coil NMR Spectroscopy – a novel tool for biological high-throughput NMR spectroscopy. Methods Mol Biol 429, 447-458(2007)
  • Herzberg, M., Kaye, I. K., Peti, W. & Wood, T. K. (2006). YdgG (TqsA) Controls Biofilm Formation in Escherichia coli K-12 through Autoinducer 2 Transport. J Bacteriol 188, 587-98.(2006)
  • Baker, K. A., Hilty, C., Peti, W., Prince, A., Pfaffinger, P. J., Wider, G., Wüthrich, K. & Choe, S. (2006). NMR-Derived Dynamic Aspects of N-Type Inactivation of a Kv Channel Suggest a Transient Interaction with the T1 Domain. Biochemistry 45, 1663-1672.(2006)
  • Kelker, M. S. & Peti, W. (2006). NMR assignment of the Spinophilin PDZ domain (493-602). J Biomol NMR 34, in press.(2006)
  • Johnson, M. A., Peti, W., Herrmann, T., Wilson, I. A. & Wüthrich, K. (2006). Solution structure of Asl1650, an acyl carrier protein from Anabaena sp. PCC 7120 with a variant phosphopantetheinylation-site sequence. Protein Sci 15, 1030-41.(2006)
  • Wirmer, J., Peti, W. & Schwalbe, H. (2006). Motional properties of unfolded ubiquitin: a model for a random coil protein. J Biomol NMR, 35 (3), 175-186.(2006)
  • Peti, W., Page, R., Moy, K., O'Neil-Johnson, M., Wilson, I. A., Stevens, R. C. & Wüthrich, K. (2005). Towards miniaturization of a structural genomics pipeline using micro-expression and microcoil NMR. J Struct Funct Genomics, 1-9.(2005)
  • Peti, W., Johnson, M. A., Herrmann, T., Neuman, B. W., Buchmeier, M. J., Nelson, M., Joseph, J., Page, R., Stevens, R. C., Kuhn, P. & Wüthrich, K. (2005). Structural Genomics of the Severe Acute Respiratory Syndrome Coronavirus: Nuclear Magnetic Resonance Structure of the Protein nsP7. J Virol 79, 12905-13.(2005)
  • Peti, W., Herrmann, T., Zagnitko, O., Grzechnik, S. K. & Wüthrich, K. (2005). NMR structure of the conserved hypothetical protein TM0979 from Thermotoga maritima. Proteins 59, 387-390.(2005)
  • Page, R., Peti, W., Wilson, I. A., Stevens, R. C. & Wüthrich, K. (2005). NMR screening and crystal quality of bacterially expressed prokaryotic and eukaryotic proteins in a structural genomics pipeline. Proc Natl Acad Sci U S A 102, 1901-5.(2005)
  • Columbus, L., Peti, W., Etezady-Esfarjani, T., Herrmann, T. & Wüthrich, K. (2005). NMR structure determination of the conserved hypothetical protein TM1816 from Thermotoga maritima. Proteins 60, 552-557.(2005)
  • Almeida, M. S., Herrmann, T., Peti, W., Wilson, I. A. & Wüthrich, K. (2005). NMR structure of the conserved hypothetical protein TM0487 from Thermotoga maritima: Implications for 216 homologous DUF59 proteins. Protein Sci 14, 2880-2886.(2005)
  • Arndt, J. W., Schwarzenbacher, R., Page, R., Abdubek, P., Ambing, E., Biorac, T., Canaves, J. M., Chiu, H. J., Dai, X., Deacon, A. M., Didonato, M., Elsliger, M. A., Godzik, A., Grittini, C., Grzechnik, S. K., Hale, J., Hampton, E., Han, G. W., Haugen, J., Hornsby, M., Klock, H. E., Koesema, E., Kreusch, A., Kuhn, P., Jaroszewski, L., Lesley, S. A., Levin, I., McMullan, D., McPhillips, T. M., Miller, M. D., Morse, A., Moy, K., Nigoghossian, E., Ouyang, J., Peti, W., Quijano, K., Reyes, R., Sims, E., Spraggon, G., Stevens, R. C., van den Bedem, H., Velasquez, J., Vincent, J., von Delft, F., Wang, X., West, B., White, A., Wolf, G., Xu, Q., Zagnitko, O., Hodgson, K. O., Wooley, J. & Wilson, I. A. (2005). Crystal structure of an alpha/beta serine hydrolase (YDR428C) from Saccharomyces cerevisiae at 1.85 A resolution. Proteins 58, 755-758.(2005)
  • Peti, W., Etezady-Esfarjani, T., Herrmann, T., Klock, H. E., Lesley, S. A. & Wüthrich, K. (2004). NMR for structural proteomics of Thermotoga maritima: screening and structure determination. J Struct Funct Genomics 5, 205-15.(2004)
  • Kelker, M. S., Foss, T. R., Peti, W., Teyton, L., Kelly, J. W., Wüthrich, K. & Wilson, I. A. (2004). Crystal Structure of Human Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1) at 1.47A. J Mol Biol 342, 1237-48.(2004)
  • Griesinger, C., Peti, W., Meiler, J. & Brüschweiler, R. (2004). Projection angle restraints for studying structure and dynamics of biomolecules. Methods Mol Biol 278, 107-122.(2004)
  • Almeida, M. S., Peti, W. & Wüthrich, K. (2004). 1H-, 13C- and 15N-NMR assignment of the conserved hypothetical protein TM0487 from Thermotoga maritima. J Biomol NMR 29, 453-4.(2004)
  • Etezady-Esfarjani, T., Herrmann, T., Peti, W., Klock, H. E., Lesley, S. A. & Wüthrich, K. (2004). NMR structure determination of the hypothetical protein TM1290 from Thermotoga maritima using automated NOESY analysis. J Biomol NMR 29, 403-6.(2004)
  • Peti, W., Norcross, J., Eldridge, G. & O'Neil-Johnson, M. (2004). Biomolecular NMR using a microcoil NMR probe--new technique for the chemical shift assignment of aromatic side chains in proteins. J Am Chem Soc 126, 5873-8.(2004)
  • Meiler, J., Peti, W. & Griesinger, C. (2003). Dipolar couplings in multiple alignments suggest alpha helical motion in ubiquitin. J Am Chem Soc 125, 8072-8073.(2003)
  • Hus, J. C., Peti, W., Griesinger, C. & Brüschweiler, R. (2003). Self-consistency analysis of dipolar couplings in multiple alignments of ubiquitin. J Am Chem Soc 125, 5596-7.(2003)
  • Griesinger, C., Meiler, J. & Peti, W. (2003). Protein NMR for the Millennium. In Biological Magnetic Resonance (Krishna, N. R. & Berliner, L. J., eds.), Vol. 20, pp. 163-229. Kluwer Academic / Plenum Press, New York.(2003)
  • Etezady-Esfarjani, T., Peti, W. & Wüthrich, K. (2003). Letter to the Editor: NMR assignment of the conserved hypothetical protein TM1290 of Thermotoga maritima. J Biomol NMR 25, 167-8.(2003)
  • Pappalardo, L., Janausch, I. G., Vijayan, V., Zientz, E., Junker, J., Peti, W., Zweckstetter, M., Unden, G. & Griesinger, C. (2003). The NMR Structure of the Sensory Domain of the Membranous Two-component Fumarate Sensor (Histidine Protein Kinase) DcuS of Escherichia coli. J. Biol. Chem. 278, 39185-39188.(2003)
  • Woschek, A., Wuggenig, F., Peti, W. & Hammerschmidt, F. (2002). On the transformation of (S)-2-hydroxypropylphosphonic acid into fosfomycin in Streptomyces fradiae--a unique method of epoxide ring formation. Chembiochem 3, 829-35.(2002)
  • Peti, W., Meiler, J., Bruschweiler, R. & Griesinger, C. (2002). Model-free analysis of protein backbone motion from residual dipolar couplings. J Am Chem Soc 124, 5822-33.(2002)
  • Parac, T. N., Coligaev, B., Zientz, E., Unden, G., Peti, W. & Griesinger, C. (2001). Assignment of 1H, 13C and 15N resonances to the sensory domain of the membraneous two-component fumarate sensor (histidine protein kinase) DcuS of Escherichia coli. J Biomol NMR 19, 91-2.(2001)
  • Neubauer, H., Meiler, J., Peti, W. & Griesinger, C. (2001). NMR Structure Determination of Saccharose and Raffinose by Means of Homo- and Heteronuclear Dipolar Couplings. Helv. Chim. Acta 84, 243-258.(2001)
  • Kramer, F., Peti, W., Griesinger, C. & Glaser, S. J. (2001). Optimized Homonuclear Carr-Purcell-Type Dipolar Mixing Sequences. J. Magn. Reson. 149, 58-66.(2001)
  • Meiler, J., Prompers, J. J., Peti, W., Griesinger, C. & Bruschweiler, R. (2001). Model-free approach to the dynamic interpretation of residual dipolar couplings in globular proteins. J Am Chem Soc 123, 6098-107.(2001)
  • Peti, W., Smith, L. J., Redfield, C. & Schwalbe, H. (2001). Chemical shifts in denatured proteins: resonance assignments for denatured ubiquitin and comparisons with other denatured proteins. J Biomol NMR 19, 153-65.(2001)
  • Peti, W., Hennig, M., Smith, L. J. & Schwalbe, H. (2000). NMR Spectroscopic Investigation of y Torsion Angle Distribution in Unfolded Ubiquitin from Analysis of 3J(Ca,Ca) Coupling Constants and Cross-Correlated GHNN,CaHa Relaxation Rates. J. Am. Chem. Soc. 122, 12017-12018.(2000)
  • Peti, W., Griesinger, C. & Bermel, W. (2000). Adiabatic TOCSY for C,C and H,H J-transfer. J Biomol NMR 18, 199-205.(2000)
  • Meiler, J., Peti, W. & Griesinger, C. (2000). DipoCoup: A versatile program for 3D-structure homology comparison based on residual dipolar couplings and pseudocontact shifts. J Biomol NMR 17, 283-94.(2000)
  • Carlomagno, T., Peti, W. & Griesinger, C. (2000). A new method for the simultaneous measurement of magnitude and sign of 1DCH and 1DHH dipolar couplings in methylene groups. J Biomol NMR 17, 99-109.(2000)
  • Peti, W. & Griesinger, C. (2000). Measurement of Magnitude and Sign of H,H-Dipolar Couplings in Proteins. J. Am. Chem. Soc. 122, 3975-3976.(2000)
  • Pieper, T., Peti, W. & Keppler, B. K. (2000). Solvolysis of the Tumor-Inhibiting Ru(III)-Complex trans-Tetrachlorobis(indazole)ruthenate(III). Metal Based Drugs 7, 225-232.(2000)
  • Peti, W., Pieper, T., Sommer, M., Keppler, B. K. & Giester, G. (1999). Synthesis of Tumor-Inhibiting Complex Salts Containing the Anion trans-Tetrachlorobis(indazole)ruthenate(III) and Crystal Structure of the Tetraphenylphosphonium Salt. Eur. J. Inorg. Chem. 1999, 1551-1555.(1999)