Vanderbilt University School of Medicine

Sanders, Charles R. II, Ph.D.
Professor of Biochemistry
Aileen M. Lange and Annie Mary Lyle Chair in Cardiovascular Research
Professor of Medicine

Lab Url: http://structbio.vanderbilt.edu/sanders/

Phone Number: (615) 936-3756

Email Address:chuck.sanders@vanderbilt.edu

Sanders, Charles's picture

Office Address   Mailing Address

5110C MRB III

Rm 5110C BIOSCI/MRBIII 37232-8725


Research Keywords
membrane proteins, disease, Charcot-Marie-Tooth, myelin, folding, misfolding, structural biology, NMR, spectroscopy, receptors, receptor, membrane, protein structure, neurodegenerative, neurodegeneration, enzymes, enzyme action, neuroscience, single nucleotide polymorphisms, SNPs, GPCRs, GPCR, G protein-coupled, Alzheimer's, neurodegenerative, kidney, potassium channels, KCNE1, integrins, amyloid, channels, biophysics, biochemistry, chemical biology

Research Specialty
Structural and chemical biology of membrane proteins. Membrane protein misfolding and disease. Alzheimer's disease, Charcot-Marie-Tooth Disease, cardiac arrhythmias, kidney fibrosis

Research Description
Molecular Biophysical Basis of Diseases Related to Membrane Protein Dysfunction and Misfolding

A surprising number of diseases are caused or impacted by missense mutations in genes encoding membrane proteins that result in protein dysfunction and/or misfolding and mistrafficking early in the secretory pathway. We seek to elucidate the molecular biophysical mechanisms by which such mutations result in these defects. Our approach is to carry out studies of purified membrane proteins under well-controlled conditions and then correlating observations from these studies with what is known about the behavior of the corresponding mutant protein in vivo. We are pursuing several systems. We have discovered that the amyloid precursor protein (APP) that is closely associated with the development of Alzheimer???s disease binds cholesterol in a way that may help to control production of the amyloid-beta polypeptide. We seek to understand exactly how and why cholesterol binds to APP and by what mechanisms this regulates amyloid-beta production. A second system involves Long QT Syndrome mutant forms of both the human KCNQ1 potassium channel and a modulatory partner, KCNE1. We are unraveling the mechanisms by which mutations in either of these proteins result in serious, even fatal cardiac arrhythmias. Another project involves a protein of the human peripheral nervous system known as peripheral myelin protein 22 (PMP22). PMP22 is known to undergo mutation-prompted misfolding which results in Charcot-Marie-Tooth Disease. We also study the integrin family or receptors that link the cell to the extracellular matrix, with a particular interest in integrins that are related to kidney function and fibrosis, as commonly occurs in type II diabetes. We also study the interactions of arrestins with G protein-coupled receptors (GPCRs). These studies employ a wide range of techniques spanning the range from molecular biophysics/spectroscopy/biochemistry to cellular/molecular biology. However, solution NMR spectroscopy is the central technique of the lab and the method for which this lab is best known. Additional information is found at the lab web site: http://structbio.vanderbilt.edu/sanders

Training in the Sanders Lab

Trainees in the Sanders lab are also broadly trained in membrane protein biochemistry and biophysics. This often involves learning practical NMR spectroscopy. Trainees are also encouraged to broader their horizons even further by interacting closely with, or even carrying out experiments in the labs of our collaborators, who are generally more physiologically-oriented that the Sanders lab. Students are also constantly exhorted to master the literature related to their project and to develop a strong biomedical perspective for their work. Finally, the PI of this lab believes that is very important for trainees to be taught the ins and outs of the research culture, including funding strategies, peer review service, and how to be a good collaborator and colleague. See, for example the document "What is Expected of a Ph.D. Student or Postdoctoral Fellow in the Sanders Lab?" which can be view on-line at: http://structbio.vanderbilt.edu/sanders/Sanders_Lab_Guide_Comprehensive.pdf

Publications
Barrett, PJ, Song, Y, Van Horn, WD, Hustedt, EJ, Schafer, JM, Hadziselimovic, A, Beel, AJ, Sanders, CR. The amyloid precursor protein has a flexible transmembrane domain and binds cholesterol. Science, 336(6085), 1168-71, 2012.

Deatherage, CL, Hadziselimovic, A, Sanders, CR. Purification and Characterization of the Human I?-Secretase Activating Protein. Biochemistry, 51(25), 5153-9, 2012.

Lu, Z, Van Horn, WD, Chen, J, Mathew, S, Zent, R, Sanders, CR. Bicelles at low concentrations. Mol Pharm, 9(4), 752-61, 2012.

Mathew, S, Lu, Z, Palamuttam, RJ, Mernaugh, G, Hadziselimovic, A, Chen, J, Bulus, N, Gewin, LS, Voehler, M, Meves, A, Ballestrem, C, F??ssler, R, Pozzi, A, Sanders, CR, Zent, R. ??1 integrin NPXY motifs regulate kidney collecting-duct development and maintenance by induced-fit interactions with cytosolic proteins. Mol Cell Biol, 32(20), 4080-91, 2012.

Mittendorf, KF, Deatherage, CL, Ohi, MD, Sanders, CR. Tailoring of Membrane Proteins by Alternative Splicing of Pre-mRNA. Biochemistry, , , 2012.

Van Horn, WD, Sanders, CR. Prokaryotic diacylglycerol kinase and undecaprenol kinase. Annu Rev Biophys, 41, 81-101, 2012.

Yang, T, Smith, JA, Leake, BF, Sanders, CR, Meiler, J, Roden, DM. An Allosteric Mechanism for Drug Block of the Human Cardiac Potassium Channel KCNQ1. Mol Pharmacol, , , 2012.

Barrett, PJ, Sanders, CR, Kaufman, SA, Michelsen, K, Jordan, JB. NSAID-based I?-secretase modulators do not bind to the amyloid-I? polypeptide. Biochemistry, 50(47), 10328-42, 2011.

Downey, JD, Sanders, CR, Breyer, RM. Evidence for the presence of a critical disulfide bond in the mouse EP3I? receptor. Prostaglandins Other Lipid Mediat, 94(1-2), 53-8, 2011. PMCID:3065360

Sakakura, M, Hadziselimovic, A, Wang, Z, Schey, KL, Sanders, CR. Structural basis for the Trembler-J phenotype of Charcot-Marie-Tooth disease. Structure, 19(8), 1160-9, 2011.

Sanders, CR, Mittendorf, KF. Tolerance to changes in membrane lipid composition as a selected trait of membrane proteins. Biochemistry, 50(37), 7858-67, 2011.

Van Horn, WD, Vanoye, CG, Sanders, CR. Working model for the structural basis for KCNE1 modulation of the KCNQ1 potassium channel. Curr Opin Struct Biol, 21(2), 283-91, 2011. PMCID:3070781

Zhuang, T, Jap, BK, Sanders, CR. Solution NMR approaches for establishing specificity of weak heterodimerization of membrane proteins. J Am Chem Soc, 133(50), 20571-80, 2011.

Beel, AJ, Sakakura, M, Barrett, PJ, Sanders, CR. Direct binding of cholesterol to the amyloid precursor protein: An important interaction in lipid-Alzheimer''s disease relationships. Biochim Biophys Acta, 1801(8), 975-82, 2010. PMCID:2886191

Borza, CM, Chen, X, Mathew, S, Mont, S, Sanders, CR, Zent, R, Pozzi, A. Integrin {alpha}1{beta}1 promotes caveolin-1 dephosphorylation by activating T cell protein-tyrosine phosphatase. J Biol Chem, 285(51), 40114-24, 2010. PMCID:3000994

Howell, SC, Mittal, R, Huang, L, Travis, B, Breyer, RM, Sanders, CR. CHOBIMALT: a cholesterol-based detergent. Biochemistry, 49(44), 9572-83, 2010. PMCID:3030671

Kang, C, Vanoye, CG, Welch, RC, Van Horn, WD, Sanders, CR. Functional delivery of a membrane protein into oocyte membranes using bicelles. Biochemistry, 49(4), 653-5, 2010. PMCID:2811756

Kelley, KD, Olive, LQ, Hadziselimovic, A, Sanders, CR. Look and see if it is time to induce protein expression in Escherichia coli cultures. Biochemistry, 49(26), 5405-7, 2010. PMCID:2896908

Koehler, J, Sulistijo, ES, Sakakura, M, Kim, HJ, Ellis, CD, Sanders, CR. Lysophospholipid micelles sustain the stability and catalytic activity of diacylglycerol kinase in the absence of lipids. Biochemistry, 49(33), 7089-99, 2010. PMCID:2923640

Vanoye, CG, Welch, RC, Tian, C, Sanders, CR, George, AL. KCNQ1/KCNE1 assembly, co-translation not required. Channels (Austin), 4(2), 108-14, 2010. PMCID:3045044

Zhuang, T, Vishnivetskiy, SA, Gurevich, VV, Sanders, CR. Elucidation of inositol hexaphosphate and heparin interaction sites and conformational changes in arrestin-1 by solution nuclear magnetic resonance. Biochemistry, 49(49), 10473-85, 2010. PMCID:3074303

Beel, AJ, Barrett, P, Schnier, PD, Hitchcock, SA, Bagal, D, Sanders, CR, Jordan, JB. Nonspecificity of binding of gamma-secretase modulators to the amyloid precursor protein. Biochemistry, 48(50), 11837-9, 2009. PMCID:2794937

Koehler, J, Woetzel, N, Staritzbichler, R, Sanders, CR, Meiler, J. A unified hydrophobicity scale for multispan membrane proteins. Proteins, 76(1), 13-29, 2009. PMCID:2761718

Li, Q, Mittal, R, Huang, L, Travis, B, Sanders, CR. Bolaamphiphile-class surfactants can stabilize and support the function of solubilized integral membrane proteins. Biochemistry, 48(49), 11606-8, 2009.

Van Horn, WD, Beel, AJ, Kang, C, Sanders, CR. The impact of window functions on NMR-based paramagnetic relaxation enhancement measurements in membrane proteins. Biochim Biophys Acta, , , 2009.

Van Horn, WD, Kim, HJ, Ellis, CD, Hadziselimovic, A, Sulistijo, ES, Karra, MD, Tian, C, S??nnichsen, FD, Sanders, CR. Solution nuclear magnetic resonance structure of membrane-integral diacylglycerol kinase. Science, 324(5935), 1726-9, 2009.

Vanacore, R, Ham, AJ, Voehler, M, Sanders, CR, Conrads, TP, Veenstra, TD, Sharpless, KB, Dawson, PE, Hudson, BG. A sulfilimine bond identified in collagen IV. Science, 325(5945), 1230-4, 2009.

Vanoye, CG, Welch, RC, Daniels, MA, Manderfield, LJ, Tapper, AR, Sanders, CR, George, AL. Distinct subdomains of the KCNQ1 S6 segment determine channel modulation by different KCNE subunits. J Gen Physiol, 134(3), 207-17, 2009.

Abair, TD, Sundaramoorthy, M, Chen, D, Heino, J, Ivaska, J, Hudson, BG, Sanders, CR, Pozzi, A, Zent, R. Cross-talk between integrins alpha1beta1 and alpha2beta1 in renal epithelial cells. Exp Cell Res, 314(19), 3593-604, 2008. PMCID:2729514

Beel, AJ, Mobley, CK, Kim, HJ, Tian, F, Hadziselimovic, A, Jap, B, Prestegard, JH, Sanders, CR. Structural studies of the transmembrane C-terminal domain of the amyloid precursor protein (APP): does APP function as a cholesterol sensor. Biochemistry, 47(36), 9428-46, 2008. PMCID:2572687

Beel, AJ, Sanders, CR. Substrate specificity of gamma-secretase and other intramembrane proteases. Cell Mol Life Sci, 65(9), 1311-34, 2008. PMCID:2569971

Kang, C, Tian, C, S??nnichsen, FD, Smith, JA, Meiler, J, George, AL, Vanoye, CG, Kim, HJ, Sanders, CR. Structure of KCNE1 and implications for how it modulates the KCNQ1 potassium channel. Biochemistry, 47(31), 7999-8006, 2008. PMCID:2580054

Myers, JK, Mobley, CK, Sanders, CR. The peripheral neuropathy-linked Trembler and Trembler-J mutant forms of peripheral myelin protein 22 are folding-destabilized. Biochemistry, 47(40), 10620-9, 2008. PMCID:2566783

Mobley, CK, Myers, JK, Hadziselimovic, A, Ellis, CD, Sanders, CR. Purification and initiation of structural characterization of human peripheral myelin protein 22, an integral membrane protein linked to peripheral neuropathies. Biochemistry, 46(39), 11185-95, 2007.

Sanders, CR. Visiting order on membrane proteins by using nanotechnology. Proc Natl Acad Sci U S A, 104(16), 6502-3, 2007. PMCID:1871815

Smith, JA, Vanoye, CG, George, AL, Meiler, J, Sanders, CR. Structural models for the KCNQ1 voltage-gated potassium channel. Biochemistry, 46(49), 14141-52, 2007. PMCID:2565492

Tian, C, Vanoye, CG, Kang, C, Welch, RC, Kim, HJ, George, AL, Sanders, CR. Preparation, functional characterization, and NMR studies of human KCNE1, a voltage-gated potassium channel accessory subunit associated with deafness and long QT syndrome. Biochemistry, 46(41), 11459-72, 2007. PMCID:2565491

Mi, D, Kim, HJ, Hadziselimovic, A, Sanders, CR. Irreversible misfolding of diacylglycerol kinase is independent of aggregation and occurs prior to trimerization and membrane association. Biochemistry, 45(33), 10072-84, 2006.

Sanders, CR, S??nnichsen, F. Solution NMR of membrane proteins: practice and challenges. Magn Reson Chem, 44 Spec No, S24-40, 2006.

Tian, C, Breyer, RM, Kim, HJ, Karra, MD, Friedman, DB, Karpay, A, Sanders, CR. Solution NMR spectroscopy of the human vasopressin V2 receptor, a G protein-coupled receptor. J Am Chem Soc, 127(22), 8010-1, 2005.

Tian, C, Karra, MD, Ellis, CD, Jacob, J, Oxenoid, K, S??nnichsen, F, Sanders, CR. Membrane protein preparation for TROSY NMR screening. Methods Enzymol, 394, 321-34, 2005.

Myers, Jeffrey K, Beihoffer, Lauren A, Sanders, Charles R. Phenotology of disease-linked proteins. Hum Mutat, 25(1), 90-97, 2004.

Nagy, Joanna K, Sanders, Charles R. Destabilizing mutations promote membrane protein misfolding. Biochemistry, 43(1), 19-25, 2004.

Oxenoid, Kirill, Kim, Hak Jun, Jacob, Jaison, S??nnichsen, Frank D, Sanders, Charles R. NMR Assignments for a Helical 40 kDa Membrane Protein. J Am Chem Soc, 126(16), 5048-9, 2004.

Sanders, Charles R, Kuhn Hoffmann, Amy, Gray, Don N, Keyes, Melvin H, Ellis, Charles D. French swimwear for membrane proteins. Chembiochem, 5(4), 423-6, 2004.

Sanders, Charles R, Myers, Jeffrey K. Disease-related misassembly of membrane proteins. Annu Rev Biophys Biomol Struct, 33, 25-51, 2004.

Gorzelle, Bonnie M, Hoffman, Amy Kuhn, Keyes, Melvin H, Gray, Don N, Ray, Dale G, Sanders, Charles R. Amphipols can support the activity of a membrane enzyme. J Am Chem Soc, 124(39), 11594-5, 2002.

Luchette, P.A., Prosser, R.S., and Sanders, C.R. Oxygen as a paramagnetic probe of membrane protein structure by cysteine mutagenesis and 19f NMR spectroscopy. J. American Chemical Society, 124, 1778-1781, 2002.

Luchette, PA, Prosser, RS, Sanders, CR. Oxygen as a paramagnetic probe of membrane protein structure by cysteine mutagenesis and (19)F NMR spectroscopy. J Am Chem Soc, 124(8), 1778-81, 2002.

Nagy, Joanna K, Sanders, Charles R. A critical residue in the folding pathway of an integral membrane protein. Biochemistry, 41(29), 9021-5, 2002.

Oxenoid, Kirill, S??nnichsen, Frank D, Sanders, Charles R. Topology and secondary structure of the N-terminal domain of diacylglycerol kinase. Biochemistry, 41(42), 12876-82, 2002.

Nagy, J K, Kuhn Hoffmann, A, Keyes, M H, Gray, D N, Oxenoid, K, Sanders, C R. Use of amphipathic polymers to deliver a membrane protein to lipid bilayers. FEBS Lett, 501(2-3), 115-20, 2001.

Nagy, J K, Lonzer, W L, Sanders, C R. Kinetic study of folding and misfolding of diacylglycerol kinase in model membranes. Biochemistry, 40(30), 8971-80, 2001.

Oxenoid, K, S??nnichsen, FD, Sanders, CR. Conformationally specific misfolding of an integral membrane protein. Biochemistry, 40(17), 5111-8, 2001.

Sanders, C R, Ismail-Beigi, F, McEnery, M W. Mutations of peripheral myelin protein 22 result in defective trafficking through mechanisms which may be common to diseases involving tetraspan membrane proteins. Biochemistry, 40(32), 9453-9, 2001.

Czerski, L, Sanders, C R. Functionality of a membrane protein in bicelles. Anal Biochem, 284(2), 327-33, 2000.

Czerski, L, Vinogradova, O, Sanders, CR. NMR-Based amide hydrogen-deuterium exchange measurements for complex membrane proteins: development and critical evaluation. J Magn Reson, 142(1), 111-9, 2000.

Czerski, L.,Sanders, C.R. Thiol modification of membrane proteins dependence upon protein site membrane disposition and reagent hydrophobicity. FEBS Letters, 472, 225-229, 2000.

L. Czerski, O. Vinogradova, and C.R. Sanders. NMR-based amide hydrogen-deuterium exchange measurements for complex membrane proteins: development and critical evaluation. J. of Magnetic Resonance, 142, 111-119, 2000.

Sanders, C R, Nagy, J K. Misfolding of membrane proteins in health and disease: the lady or the tiger. Curr Opin Struct Biol, 10(4), 438-42, 2000.

Sanders, C R, Oxenoid, K. Customizing model membranes and samples for NMR spectroscopic studies of complex membrane proteins. Biochim Biophys Acta, 1508(1-2), 129-45, 2000.

Gorzelle, B M, Nagy, J K, Oxenoid, K, Lonzer, W L, Cafiso, D S, Sanders, C R. Reconstitutive refolding of diacylglycerol kinase, an integral membrane protein. Biochemistry, 38(49), 16373-82, 1999.

Sanders, C R, Prosser, R S. Bicelles: a model membrane system for all seasons. Structure, 6(10), 1227-34, 1998.

Vinogradova, O, Carlin, C, Sonnichsen, F D, Sanders, C R. A membrane setting for the sorting motifs present in the adenovirus E3-13.7 protein which down-regulates the epidermal growth factor receptor. J Biol Chem, 273(28), 17343-50, 1998.

Vinogradova, O, S??nnichsen, F, Sanders, CR. On choosing a detergent for solution NMR studies of membrane proteins. J Biomol NMR, 11(4), 381-6, 1998.

Badola, P, Sanders, C R. Escherichia coli diacylglycerol kinase is an evolutionarily optimized membrane enzyme and catalyzes direct phosphoryl transfer. J Biol Chem, 272(39), 24176-82, 1997.

Vinogradova, O, Badola, P, Czerski, L, S??nnichsen, FD, Sanders, CR. Escherichia coli diacylglycerol kinase: a case study in the application of solution NMR methods to an integral membrane protein. Biophys J, 72(6), 2688-701, 1997. PMCID:1184466

Sanders, C R, Landis, G C. Reconstitution of membrane proteins into lipid-rich bilayered mixed micelles for NMR studies. Biochemistry, 34(12), 4030-40, 1995.

C. R. Sanders and G. C. Landis. Facile Acquisition and Assignment of Oriented Sample NMR Spectra for Bilayer Surface-Associated Proteins. Journal of the American Chemical Society, 116, 6470-6471 , 1994.

C. R. Sanders, B. J. Hare, K. Howard, and James H. Prestegard. Magnetically Oriented Phospholipid Micelles as a Tool for the Study of Membrane-Associated Molecules. Progress in NMR Spectroscopy, 26, 421-444, 1994.

Sanders, CR. Qualitative comparison of the bilayer-associated structures of diacylglycerol and a fluorinated analog based upon oriented sample NMR data. Chem Phys Lipids, 72(1), 41-57, 1994.

Smith, R L, O''Toole, J F, Maguire, M E, Sanders, C R. Membrane topology of Escherichia coli diacylglycerol kinase. J Bacteriol, 176(17), 5459-65, 1994. PMCID:196734

Hare, BJ, Sanders, CR, McIntyre, SE, Prestegard, JH. Synthesis and characterization of a 13C-labeled alpha-mannosyl glycolipid analog from [13C]glucose. Chem Phys Lipids, 66(1-2), 155-8, 1993.

Sanders, C R, Schwonek, J P. An approximate model and empirical energy function for solute interactions with a water-phosphatidylcholine interface. Biophys J, 65(3), 1207-18, 1993. PMCID:1225840

Sanders, CR. Solid state 13C NMR of unlabeled phosphatidylcholine bilayers: spectral assignments and measurement of carbon-phosphorus dipolar couplings and 13C chemical shift anisotropies. Biophys J, 64(1), 171-81, 1993. PMCID:1262314

Sanders, CR, Schaff, JE, Prestegard, JH. Orientational behavior of phosphatidylcholine bilayers in the presence of aromatic amphiphiles and a magnetic field. Biophys J, 64(4), 1069-80, 1993. PMCID:1262425

Sanders, CR, Schwonek, JP. Simulation of NMR data from oriented membrane proteins: practical information for experimental design. Biophys J, 65(4), 1460-9, 1993. PMCID:1225873

Ikeda-Saito, M, Hori, H, Andersson, LA, Prince, RC, Pickering, IJ, George, GN, Sanders, CR, Lutz, RS, McKelvey, EJ, Mattera, R. Coordination structure of the ferric heme iron in engineered distal histidine myoglobin mutants. J Biol Chem, 267(32), 22843-52, 1992.

Sanders, C R, Schwonek, J P. Characterization of magnetically orientable bilayers in mixtures of dihexanoylphosphatidylcholine and dimyristoylphosphatidylcholine by solid-state NMR. Biochemistry, 31(37), 8898-905, 1992.

Sanders, CR, Prestegard, JH. Magnetically orientable phospholipid bilayers containing small amounts of a bile salt analogue, CHAPSO. Biophys J, 58(2), 447-60, 1990. PMCID:1280985

Sanders, C R, Tian, G C, Tsai, M D. Mechanism of adenylate kinase. Is there a relationship between local substrate dynamics, local binding energy, and the catalytic mechanism. Biochemistry, 28(23), 9028-43, 1989.

Sanders, CR, Tsai, MD. Ligand-protein interactions via nuclear magnetic resonance of quadrupolar nuclei. Methods Enzymol, 177, 317-33, 1989.


Postdoctoral Position Available
No

Postdoctoral Position Details
N/A

Updated Date
11/22/2013



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