Department of Pharmacology

Faculty

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Shaun R Stauffer, Ph.D.

Research Assistant Professor of Pharmacology
Research Assistant Professor of Chemistry
BRET Profile (opens in a new window)
shaun.stauffer@Vanderbilt.Edu
615-936-8407
Fax: 615-343-3088
12468 MRBIV-Langford
Nashville, TN 37232-0697

Education

NIH Postdoctoral Fellow, Yale University, New Haven, CT
Ph.D., University of Illinois, Urbana, IL
B.S., Southern Illinois University, Carbondale, IL

Research Keywords

Drug Discovery, Medicinal Chemistry, CNS disorders, allosteric modulation, structure-based ligand/inhibitor design, metabotropic glutamate receptors, organometallic chemistry, reaction discovery, Schizophrenia, Alzheimera??s disease

Research Description

Dr. Stauffer's research interests lie in the areas of allosteric modulation of cell surface receptors, protein-protein interaction (PPI) cell signaling inhibitor development, and protease structure-based inhibitor design.

In addition, Dr. Stauffer is interested in organometallic chemistry and reaction discovery and its application towards enabling novel library syntheses. As Co-director within the Vanderbilt Specialized Chemistry Center for Accelerated Probe Development, which is a member of the Molecular Libraries Probe Production Centers Network (MLPCN), part of the Molecular Libraries Probe Production Centers Network (MLPCN, NIH Roadmap Initiative), Dr. Stauffera??s group utilizes medicinal chemistry principles and modern synthesis and purification tools to develop highly selective probe molecules. In addition, through an industry sponsored research contract Dr. Stauffer leads a drug discovery team within the Vanderbilt Center for Neuroscience Drug Discovery focusing on the development of novel small molecule positive allosteric modulators of the metabotropic glutamate receptor 5 (mGlu5) for the treatment of schizophrenia. Current research in this area is focused on the development of suitable backup preclinical candidate molecules.


Publications

Jacobs, J, Grum-Tokars, V, Zhou, Y, Turlington, M, Saldanha, SA, Chase, P, Eggler, A, Dawson, ES, Baez-Santos, YM, Tomar, S, Mielech, AM, Baker, SC, Lindsley, CW, Hodder, P, Mesecar, A, Stauffer, SR. Discovery, synthesis, and structure-based optimization of a series of N-(tert-butyl)-2-(N-arylamido)-2-(pyridin-3-yl) acetamides (ML188) as potent noncovalent small molecule inhibitors of the severe acute respiratory syndrome coronavirus (SARS-CoV) 3CL protease. J Med Chem, 56(2), 534-46, 2013

Rook, JM, Noetzel, MJ, Pouliot, WA, Bridges, TM, Vinson, PN, Cho, HP, Zhou, Y, Gogliotti, RD, Manka, JT, Gregory, KJ, Stauffer, SR, Dudek, FE, Xiang, Z, Niswender, CM, Daniels, JS, Jones, CK, Lindsley, CW, Conn, PJ. Unique signaling profiles of positive allosteric modulators of metabotropic glutamate receptor subtype 5 determine differences in in vivo activity. Biol Psychiatry, 73(6), 501-9, 2013

Gregory, KJ, Nguyen, ED, Reiff, SD, Squire, EF, Stauffer, SR, Lindsley, CW, Meiler, J, Conn, PJ. Probing the metabotropic glutamate receptor 5 (mGlu???) positive allosteric modulator (PAM) binding pocket: discovery of point mutations that engender a &quot;molecular switch&quot; in PAM pharmacology. Mol Pharmacol, 83(5), 991-1006, 2013

Noetzel, MJ, Gregory, KJ, Vinson, PN, Manka, JT, Stauffer, SR, Lindsley, CW, Niswender, CM, Xiang, Z, Conn, PJ. A novel metabotropic glutamate receptor 5 positive allosteric modulator acts at a unique site and confers stimulus bias to mGlu5 signaling. Mol Pharmacol, 83(4), 835-47, 2013

D''Amore, V, Santolini, I, van Rijn, CM, Biagioni, F, Molinaro, G, Prete, A, Conn, PJ, Lindsley, CW, Zhou, Y, Vinson, PN, Rodriguez, AL, Jones, CK, Stauffer, SR, Nicoletti, F, van Luijtelaar, G, Ngomba, RT. Potentiation of mGlu5 receptors with the novel enhancer, VU0360172, reduces spontaneous absence seizures in WAG/Rij rats. Neuropharmacology, 2012

Rodriguez, AL, Zhou, Y, Williams, R, David Weaver, C, Vinson, PN, Dawson, ES, Steckler, T, Lavreysen, H, Mackie, C, Bartolom??, JM, Macdonald, GJ, Scott Daniels, J, Niswender, CM, Jones, CK, Jeffrey Conn, P, Lindsley, CW, Stauffer, SR. Discovery and SAR of a novel series of non-MPEP site mGlu??? PAMs based on an aryl glycine sulfonamide scaffold. Bioorg Med Chem Lett, 22(24), 7388-92, 2012

Noetzel, MJ, Rook, JM, Vinson, PN, Cho, HP, Days, E, Zhou, Y, Rodriguez, AL, Lavreysen, H, Stauffer, SR, Niswender, CM, Xiang, Z, Daniels, JS, Jones, CK, Lindsley, CW, Weaver, CD, Conn, PJ. Functional impact of allosteric agonist activity of selective positive allosteric modulators of metabotropic glutamate receptor subtype 5 in regulating central nervous system function. Mol Pharmacol, 81(2), 120-33, 2012

Kiritoshi, T, Sun, H, Ren, W, Stauffer, SR, Lindsley, CW, Conn, PJ, Neugebauer, V. Modulation of pyramidal cell output in the medial prefrontal cortex by mGluR5 interacting with CB1. Neuropharmacology, 2012

Sheffler, DJ, Wenthur, CJ, Bruner, JA, Carrington, SJ, Vinson, PN, Gogi, KK, Blobaum, AL, Morrison, RD, Vamos, M, Cosford, ND, Stauffer, SR, Daniels, JS, Niswender, CM, Conn, PJ, Lindsley, CW. Development of a novel, CNS-penetrant, metabotropic glutamate receptor 3 (mGlu3) NAM probe (ML289) derived from a closely related mGlu5 PAM. Bioorg Med Chem Lett, 22(12), 3921-5, 2012

Manka, JT, Vinson, PN, Gregory, KJ, Zhou, Y, Williams, R, Gogi, K, Days, E, Jadhav, S, Herman, EJ, Lavreysen, H, Mackie, C, Bartolom??, JM, Macdonald, GJ, Steckler, T, Daniels, JS, Weaver, CD, Niswender, CM, Jones, CK, Conn, PJ, Lindsley, CW, Stauffer, SR. Optimization of an ether series of mGlu5 positive allosteric modulators: molecular determinants of MPEP-site interaction crossover. Bioorg Med Chem Lett, 22(20), 6481-5, 2012

Gregory, KJ, Noetzel, MJ, Rook, JM, Vinson, PN, Stauffer, SR, Rodriguez, AL, Emmitte, KA, Zhou, Y, Chun, AC, Felts, AS, Chauder, BA, Lindsley, CW, Niswender, CM, Conn, PJ. Investigating metabotropic glutamate receptor 5 allosteric modulator cooperativity, affinity, and agonism: enriching structure-function studies and structure-activity relationships. Mol Pharmacol, 82(5), 860-75, 2012

Williams, R, Manka, JT, Rodriguez, AL, Vinson, PN, Niswender, CM, Weaver, CD, Jones, CK, Conn, PJ, Lindsley, CW, Stauffer, SR. Synthesis and SAR of centrally active mGlu5 positive allosteric modulators based on an aryl acetylenic bicyclic lactam scaffold. Bioorg Med Chem Lett, 21(5), 1350-3, 2011

Stauffer, SR. Progress toward positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGlu???). ACS Chem Neurosci, 2(8), 450-70, 2011

Rodriguez, AL, Grier, MD, Jones, CK, Herman, EJ, Kane, AS, Smith, RL, Williams, R, Zhou, Y, Marlo, JE, Days, EL, Blatt, TN, Jadhav, S, Menon, UN, Vinson, PN, Rook, JM, Stauffer, SR, Niswender, CM, Lindsley, CW, Weaver, CD, Conn, PJ. Discovery of novel allosteric modulators of metabotropic glutamate receptor subtype 5 reveals chemical and functional diversity and in vivo activity in rat behavioral models of anxiolytic and antipsychotic activity. Mol Pharmacol, 78(6), 1105-23, 2010

Zhou, Y, Manka, JT, Rodriguez, AL, Weaver, CD, Days, EL, Vinson, PN, Jadhav, S, Hermann, EJ, Jones, CK, Conn, PJ, Lindsley, CW, Stauffer, SR. Discovery of N-Aryl Piperazines as Selective mGlu(5) Potentiators with Efficacy in a Rodent Model Predictive of Anti-Psychotic Activity. ACS Med Chem Lett, 1(8), 433-438, 2010

Uebele, VN, Nuss, CE, Santarelli, VP, Garson, SL, Kraus, RL, Barrow, JC, Stauffer, SR, Koblan, KS, Renger, JJ, Aton, S, Seibt, J, Dumoulin, M, Jha, SK, Coleman, T, Frank, MG. T-type calcium channels regulate cortical plasticity in-vivo. [corrected]. Neuroreport, 20(3), 257-62, 2009

Deng, JZ, Paone, DV, Ginnetti, AT, Kurihara, H, Dreher, SD, Weissman, SA, Stauffer, SR, Burgey, CS. Copper-facilitated Suzuki reactions: application to 2-heterocyclic boronates. Org Lett, 11(2), 345-7, 2009

Nantermet, PG, Rajapakse, HA, Stanton, MG, Stauffer, SR, Barrow, JC, Gregro, AR, Moore, KP, Steinbeiser, MA, Swestock, J, Selnick, HG, Graham, SL, McGaughey, GB, Colussi, D, Lai, MT, Sankaranarayanan, S, Simon, AJ, Munshi, S, Cook, JJ, Holahan, MA, Michener, MS, Vacca, JP. Evolution of tertiary carbinamine BACE-1 inhibitors: Abeta reduction in rhesus CSF upon oral dosing. ChemMedChem, 4(1), 37-40, 2009

Barrow, JC, Stauffer, SR, Rittle, KE, Ngo, PL, Yang, Z, Selnick, HG, Graham, SL, Munshi, S, McGaughey, GB, Holloway, MK, Simon, AJ, Price, EA, Sankaranarayanan, S, Colussi, D, Tugusheva, K, Lai, MT, Espeseth, AS, Xu, M, Huang, Q, Wolfe, A, Pietrak, B, Zuck, P, Levorse, DA, Hazuda, D, Vacca, JP. Discovery and X-ray crystallographic analysis of a spiropiperidine iminohydantoin inhibitor of beta-secretase. J Med Chem, 51(20), 6259-62, 2008

Stanton, MG, Stauffer, SR, Gregro, AR, Steinbeiser, M, Nantermet, P, Sankaranarayanan, S, Price, EA, Wu, G, Crouthamel, MC, Ellis, J, Lai, MT, Espeseth, AS, Shi, XP, Jin, L, Colussi, D, Pietrak, B, Huang, Q, Xu, M, Simon, AJ, Graham, SL, Vacca, JP, Selnick, H. Discovery of isonicotinamide derived beta-secretase inhibitors: in vivo reduction of beta-amyloid. J Med Chem, 50(15), 3431-3, 2007

Stauffer, SR, Stanton, MG, Gregro, AR, Steinbeiser, MA, Shaffer, JR, Nantermet, PG, Barrow, JC, Rittle, KE, Collusi, D, Espeseth, AS, Lai, MT, Pietrak, BL, Holloway, MK, McGaughey, GB, Munshi, SK, Hochman, JH, Simon, AJ, Selnick, HG, Graham, SL, Vacca, JP. Discovery and SAR of isonicotinamide BACE-1 inhibitors that bind beta-secretase in a N-terminal 10s-loop down conformation. Bioorg Med Chem Lett, 17(6), 1788-92, 2007

McGaughey, GB, Colussi, D, Graham, SL, Lai, MT, Munshi, SK, Nantermet, PG, Pietrak, B, Rajapakse, HA, Selnick, HG, Stauffer, SR, Holloway, MK. Beta-secretase (BACE-1) inhibitors: accounting for 10s loop flexibility using rigid active sites. Bioorg Med Chem Lett, 17(4), 1117-21, 2007

Stauffer, SR. Small molecule inhibition of the Bcl-X(L)-BH3 protein-protein interaction: proof-of-concept of an in vivo chemopotentiator ABT-737. Curr Top Med Chem, 7(10), 961-5, 2007

Stauffer, SR, Hartwig, JF. Fluorescence resonance energy transfer (FRET) as a high-throughput assay for coupling reactions. Arylation of amines as a case study. J Am Chem Soc, 125(23), 6977-85, 2003

Barrow, JC, Nantermet, PG, Stauffer, SR, Ngo, PL, Steinbeiser, MA, Mao, SS, Carroll, SS, Bailey, C, Colussi, D, Bosserman, M, Burlein, C, Cook, JJ, Sitko, G, Tiller, PR, Miller-Stein, CM, Rose, M, McMasters, DR, Vacca, JP, Selnick, HG. Synthesis and evaluation of imidazole acetic acid inhibitors of activated thrombin-activatable fibrinolysis inhibitor as novel antithrombotics. J Med Chem, 46(25), 5294-7, 2003

Stauffer, SR, Huang, YR, Aron, ZD, Coletta, CJ, Sun, J, Katzenellenbogen, BS, Katzenellenbogen, JA. Triarylpyrazoles with basic side chains: development of pyrazole-based estrogen receptor antagonists. Bioorg Med Chem, 9(1), 151-61, 2001

Stambuli, JP, Stauffer, SR, Shaughnessy, KH, Hartwig, JF. Screening of homogeneous catalysts by fluorescence resonance energy transfer. Identification of catalysts for room-temperature Heck reactions. J Am Chem Soc, 123(11), 2677-8, 2001

Stauffer, SR, Beare, NA, Stambuli, JP, Hartwig, JF. Palladium-catalyzed arylation of ethyl cyanoacetate. Fluorescence resonance energy transfer as a tool for reaction discovery. J Am Chem Soc, 123(19), 4641-2, 2001

Stauffer, SR, Huang, Y, Coletta, CJ, Tedesco, R, Katzenellenbogen, JA. Estrogen pyrazoles: defining the pyrazole core structure and the orientation of substituents in the ligand binding pocket of the estrogen receptor. Bioorg Med Chem, 9(1), 141-50, 2001