Jürgen Wess, Ph.D.

Section Chief: Molecular Signaling Section, Laboratory of Bioorganic Chemistry

Scientific Focus Areas: Cell Biology, Molecular Biology and Biochemistry, Molecular Pharmacology, Chemical Biology

jurgenw@niddk.nih.gov 301-402-3589 Add to Contacts

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Publications

A selection of recent and significant publications can be viewed below.

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Adipocyte G(q) signaling is a regulator of glucose and lipid homeostasis in mice.

Kimura T, Pydi SP, Wang L, Haspula D, Cui Y, Lu H, König GM, Kostenis E, Steinberg GR, Gavrilova O, Wess J.

Nat Commun (2022 Mar 29) 13:1652. Abstract/Full Text

Clenbuterol exerts antidiabetic activity through metabolic reprogramming of skeletal muscle cells.

Meister J, Bone DBJ, Knudsen JR, Barella LF, Velenosi TJ, Akhmedov D, Lee RJ, Cohen AH, Gavrilova O, Cui Y, Karsenty G, Chen M, Weinstein LS, Kleinert M, Berdeaux R, Jensen TE, Richter EA, Wess J.

Nat Commun (2022 Jan 10) 13:22. Abstract/Full Text

Beneficial metabolic role of β-arrestin-1 expressed by AgRP neurons.

Pydi SP, Cui Z, He Z, Barella LF, Pham J, Cui Y, Oberlin DJ, Egritag HE, Urs N, Gavrilova O, Schwartz GJ, Buettner C, Williams KW, Wess J.

Sci Adv (2020 Jun) 6:eaaz1341. Abstract/Full Text

β-arrestin-1 suppresses myogenic reprogramming of brown fat to maintain euglycemia.

Pydi SP, Jain S, Barella LF, Zhu L, Sakamoto W, Meister J, Wang L, Lu H, Cui Y, Gavrilova O, Wess J.

Sci Adv (2020 Jun) 6:eaba1733. Abstract/Full Text

Adipocyte G(i) signaling is essential for maintaining whole-body glucose homeostasis and insulin sensitivity.

Wang L, Pydi SP, Zhu L, Barella LF, Cui Y, Gavrilova O, Bence KK, Vernochet C, Wess J.

Nat Commun (2020 Jun 12) 11:2995. Abstract/Full Text

Additional Publications

Allosteric modulation of β-cell M(3) muscarinic acetylcholine receptors greatly improves glucose homeostasis in lean and obese mice.

Zhu L, Rossi M, Cohen A, Pham J, Zheng H, Dattaroy D, Mukaibo T, Melvin JE, Langel JL, Hattar S, Matschinsky FM, Appella DH, Doliba NM, Wess J.

Proc Natl Acad Sci U S A (2019 Sep 10) 116:18684-18690. Abstract/Full Text

β-Cell-intrinsic β-arrestin 1 signaling enhances sulfonylurea-induced insulin secretion.

Barella LF, Rossi M, Zhu L, Cui Y, Mei FC, Cheng X, Chen W, Gurevich VV, Wess J.

J Clin Invest (2019 Jun 11) 129:3732-3737. Abstract/Full Text

Intra-islet glucagon signaling is critical for maintaining glucose homeostasis.

Zhu L, Dattaroy D, Pham J, Wang L, Barella LF, Cui Y, Wilkins KJ, Roth BL, Hochgeschwender U, Matschinsky FM, Kaestner KH, Doliba NM, Wess J.

JCI Insight (2019 Apr 23) 5. Abstract/Full Text

Muscarinic Receptor M(3)R Signaling Prevents Efficient Remyelination by Human and Mouse Oligodendrocyte Progenitor Cells.

Welliver RR, Polanco JJ, Seidman RA, Sinha AK, O'Bara MA, Khaku ZM, Santiago González DA, Nishiyama A, Wess J, Feltri ML, Paez PM, Sim FJ.

J Neurosci (2018 Aug 1) 38:6921-6932. Abstract/Full Text

Muscarinic receptors 2 and 5 regulate bitter response of urethral brush cells via negative feedback.

Deckmann K, Rafiq A, Erdmann C, Illig C, Durschnabel M, Wess J, Weidner W, Bschleipfer T, Kummer W.

FASEB J (2018 Jun) 32:2903-2910. Abstract/Full Text

Muscarinic M4 Receptors on Cholinergic and Dopamine D1 Receptor-Expressing Neurons Have Opposing Functionality for Positive Reinforcement and Influence Impulsivity.

Klawonn AM, Wilhelms DB, Lindström SH, Singh AK, Jaarola M, Wess J, Fritz M, Engblom D.

Front Mol Neurosci (2018) 11:139. Abstract/Full Text

Lack of beta-arrestin signaling in the absence of active G proteins.

Grundmann M, Merten N, Malfacini D, Inoue A, Preis P, Simon K, Rüttiger N, Ziegler N, Benkel T, Schmitt NK, Ishida S, Müller I, Reher R, Kawakami K, Inoue A, Rick U, Kühl T, Imhof D, Aoki J, König GM, Hoffmann C, Gomeza J, Wess J, Kostenis E.

Nat Commun (2018 Jan 23) 9:341. Abstract/Full Text

Cognitive enhancement and antipsychotic-like activity following repeated dosing with the selective M(4) PAM VU0467154.

Gould RW, Grannan MD, Gunter BW, Ball J, Bubser M, Bridges TM, Wess J, Wood MW, Brandon NJ, Duggan ME, Niswender CM, Lindsley CW, Conn PJ, Jones CK.

Neuropharmacology (2018 Jan) 128:492-502. Abstract/Full Text

Cholinergic Projections to the Substantia Nigra Pars Reticulata Inhibit Dopamine Modulation of Basal Ganglia through the M(4) Muscarinic Receptor.

Moehle MS, Pancani T, Byun N, Yohn SE, Wilson GH 3rd, Dickerson JW, Remke DH, Xiang Z, Niswender CM, Wess J, Jones CK, Lindsley CW, Rook JM, Conn PJ.

Neuron (2017 Dec 20) 96:1358-1372.e4. Abstract/Full Text

Atropine augments cardiac contractility by inhibiting cAMP-specific phosphodiesterase type 4.

Perera RK, Fischer TH, Wagner M, Dewenter M, Vettel C, Bork NI, Maier LS, Conti M, Wess J, El-Armouche A, Hasenfuß G, Nikolaev VO.

Sci Rep (2017 Nov 9) 7:15222. Abstract/Full Text

Hepatic β-arrestin 2 is essential for maintaining euglycemia.

Zhu L, Rossi M, Cui Y, Lee RJ, Sakamoto W, Perry NA, Urs NM, Caron MG, Gurevich VV, Godlewski G, Kunos G, Chen M, Chen W, Wess J.

J Clin Invest (2017 Aug 1) 127:2941-2945. Abstract/Full Text

M1 muscarinic allosteric modulators slow prion neurodegeneration and restore memory loss.

Bradley SJ, Bourgognon JM, Sanger HE, Verity N, Mogg AJ, White DJ, Butcher AJ, Moreno JA, Molloy C, Macedo-Hatch T, Edwards JM, Wess J, Pawlak R, Read DJ, Sexton PM, Broad LM, Steinert JR, Mallucci GR, Christopoulos A, Felder CC, Tobin AB.

J Clin Invest (2017 Feb 1) 127:487-499. Abstract/Full Text

β-arrestin-2 is an essential regulator of pancreatic β-cell function under physiological and pathophysiological conditions.

Zhu L, Almaça J, Dadi PK, Hong H, Sakamoto W, Rossi M, Lee RJ, Vierra NC, Lu H, Cui Y, McMillin SM, Perry NA, Gurevich VV, Lee A, Kuo B, Leapman RD, Matschinsky FM, Doliba NM, Urs NM, Caron MG, Jacobson DA, Caicedo A, Wess J.

Nat Commun (2017 Feb 1) 8:14295. Abstract/Full Text

Muscarinic acetylcholine receptors act in synergy to facilitate learning and memory.

Leaderbrand K, Chen HJ, Corcoran KA, Guedea AL, Jovasevic V, Wess J, Radulovic J.

Learn Mem (2016 Nov) 23:631-638. Abstract/Full Text

Accelerated remyelination during inflammatory demyelination prevents axonal loss and improves functional recovery.

Mei F, Lehmann-Horn K, Shen YA, Rankin KA, Stebbins KJ, Lorrain DS, Pekarek K, A Sagan S, Xiao L, Teuscher C, von Büdingen HC, Wess J, Lawrence JJ, Green AJ, Fancy SP, Zamvil SS, Chan JR.

Elife (2016 Sep 27) 5. Abstract/Full Text

Use of Designer G Protein-Coupled Receptors to Dissect Metabolic Pathways.

Wess J.

Trends Endocrinol Metab (2016 Sep) 27:600-603. Abstract/Full Text

M4 Muscarinic Receptor Signaling Ameliorates Striatal Plasticity Deficits in Models of L-DOPA-Induced Dyskinesia.

Shen W, Plotkin JL, Francardo V, Ko WK, Xie Z, Li Q, Fieblinger T, Wess J, Neubig RR, Lindsley CW, Conn PJ, Greengard P, Bezard E, Cenci MA, Surmeier DJ.

Neuron (2016 Jun 1) 90:1139. Abstract/Full Text

A G Protein-biased Designer G Protein-coupled Receptor Useful for Studying the Physiological Relevance of Gq/11-dependent Signaling Pathways.

Hu J, Stern M, Gimenez LE, Wanka L, Zhu L, Rossi M, Meister J, Inoue A, Beck-Sickinger AG, Gurevich VV, Wess J.

J Biol Chem (2016 Apr 8) 291:7809-20. Abstract/Full Text

The Gq signalling pathway inhibits brown and beige adipose tissue.

Klepac K, Kilić A, Gnad T, Brown LM, Herrmann B, Wilderman A, Balkow A, Glöde A, Simon K, Lidell ME, Betz MJ, Enerbäck S, Wess J, Freichel M, Blüher M, König G, Kostenis E, Insel PA, Pfeifer A.

Nat Commun (2016 Mar 9) 7:10895. Abstract/Full Text

Corrigendum: Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake.

Nakajima K, Cui Z, Li C, Meister J, Cui Y, Fu O, Smith AS, Jain S, Lowell BB, Krashes MJ, Wess J.

Nat Commun (2016 Mar 3) 7:11019. Abstract/Full Text

CK2 acts as a potent negative regulator of receptor-mediated insulin release in vitro and in vivo.

Rossi M, Ruiz de Azua I, Barella LF, Sakamoto W, Zhu L, Cui Y, Lu H, Rebholz H, Matschinsky FM, Doliba NM, Butcher AJ, Tobin AB, Wess J.

Proc Natl Acad Sci U S A (2015 Dec 8) 112:E6818-24. Abstract/Full Text

M4 Muscarinic Receptor Signaling Ameliorates Striatal Plasticity Deficits in Models of L-DOPA-Induced Dyskinesia.

Shen W, Plotkin JL, Francardo V, Ko WK, Xie Z, Li Q, Fieblinger T, Wess J, Neubig RR, Lindsley CW, Conn PJ, Greengard P, Bezard E, Cenci MA, Surmeier DJ.

Neuron (2015 Nov 18) 88:762-73. Abstract/Full Text

Role for the M1 Muscarinic Acetylcholine Receptor in Top-Down Cognitive Processing Using a Touchscreen Visual Discrimination Task in Mice.

Gould RW, Dencker D, Grannan M, Bubser M, Zhan X, Wess J, Xiang Z, Locuson C, Lindsley CW, Conn PJ, Jones CK.

ACS Chem Neurosci (2015 Oct 21) 6:1683-95. Abstract/Full Text

Muscarinic regulation of dopamine and glutamate transmission in the nucleus accumbens.

Shin JH, Adrover MF, Wess J, Alvarez VA.

Proc Natl Acad Sci U S A (2015 Jun 30) 112:8124-9. Abstract/Full Text

The M3 muscarinic receptor is required for optimal adaptive immunity to helminth and bacterial infection.

Darby M, Schnoeller C, Vira A, Culley FJ, Bobat S, Logan E, Kirstein F, Wess J, Cunningham AF, Brombacher F, Selkirk ME, Horsnell WG.

PLoS Pathog (2015 Jan) 11:e1004636. Abstract/Full Text

Muscarinic M3 receptors on structural cells regulate cigarette smoke-induced neutrophilic airway inflammation in mice.

Kistemaker LE, van Os RP, Dethmers-Ausema A, Bos IS, Hylkema MN, van den Berge M, Hiemstra PS, Wess J, Meurs H, Kerstjens HA, Gosens R.

Am J Physiol Lung Cell Mol Physiol (2015 Jan 1) 308:L96-103. Abstract/Full Text

Virus-Mediated Expression of DREADDs for In Vivo Metabolic Studies.

Rossi M, Cui Z, Nakajima K, Hu J, Zhu L, Wess J.

Methods Mol Biol (2015) 1335:205-21. Abstract/Full Text

Gigantism and acromegaly due to Xq26 microduplications and GPR101 mutation.

Trivellin G, Daly AF, Faucz FR, Yuan B, Rostomyan L, Larco DO, Schernthaner-Reiter MH, Szarek E, Leal LF, Caberg JH, Castermans E, Villa C, Dimopoulos A, Chittiboina P, Xekouki P, Shah N, Metzger D, Lysy PA, Ferrante E, Strebkova N, Mazerkina N, Zatelli MC, Lodish M, Horvath A, de Alexandre RB, Manning AD, Levy I, Keil MF, Sierra Mde L, Palmeira L, Coppieters W, Georges M, Naves LA, Jamar M, Bours V, Wu TJ, Choong CS, Bertherat J, Chanson P, Kamenický P, Farrell WE, Barlier A, Quezado M, Bjelobaba I, Stojilkovic SS, Wess J, Costanzi S, Liu P, Lupski JR, Beckers A, Stratakis CA.

N Engl J Med (2014 Dec 18) 371:2363-74. Abstract/Full Text

Selective activation of M4 muscarinic acetylcholine receptors reverses MK-801-induced behavioral impairments and enhances associative learning in rodents.

Bubser M, Bridges TM, Dencker D, Gould RW, Grannan M, Noetzel MJ, Lamsal A, Niswender CM, Daniels JS, Poslusney MS, Melancon BJ, Tarr JC, Byers FW, Wess J, Duggan ME, Dunlop J, Wood MW, Brandon NJ, Wood MR, Lindsley CW, Conn PJ, Jones CK.

ACS Chem Neurosci (2014 Oct 15) 5:920-42. Abstract/Full Text

Novel insights into M3 muscarinic acetylcholine receptor physiology and structure.

Kruse AC, Li J, Hu J, Kobilka BK, Wess J.

J Mol Neurosci (2014 Jul) 53:316-23. Abstract/Full Text

Combination of secretin and fluvastatin ameliorates the polyuria associated with X-linked nephrogenic diabetes insipidus in mice.

Procino G, Milano S, Carmosino M, Barbieri C, Nicoletti MC, Li JH, Wess J, Svelto M.

Kidney Int (2014 Jul) 86:127-38. Abstract/Full Text

Antipsychotic drug-like effects of the selective M4 muscarinic acetylcholine receptor positive allosteric modulator VU0152100.

Byun NE, Grannan M, Bubser M, Barry RL, Thompson A, Rosanelli J, Gowrishankar R, Kelm ND, Damon S, Bridges TM, Melancon BJ, Tarr JC, Brogan JT, Avison MJ, Deutch AY, Wess J, Wood MR, Lindsley CW, Gore JC, Conn PJ, Jones CK.

Neuropsychopharmacology (2014 Jun) 39:1578-93. Abstract/Full Text

Genome-wide association mapping of acute lung injury in neonatal inbred mice.

Nichols JL, Gladwell W, Verhein KC, Cho HY, Wess J, Suzuki O, Wiltshire T, Kleeberger SR.

FASEB J (2014 Jun) 28:2538-50. Abstract/Full Text

Muscarinic acetylcholine receptor X-ray structures: potential implications for drug development.

Kruse AC, Hu J, Kobilka BK, Wess J.

Curr Opin Pharmacol (2014 Jun) 16:24-30. Abstract/Full Text

Differential regulation of primary afferent input to spinal cord by muscarinic receptor subtypes delineated using knockout mice.

Chen SR, Chen H, Yuan WX, Wess J, Pan HL.

J Biol Chem (2014 May 16) 289:14321-30. Abstract/Full Text

Muscarinic M₃ receptors contribute to allergen-induced airway remodeling in mice.

Kistemaker LE, Bos ST, Mudde WM, Hylkema MN, Hiemstra PS, Wess J, Meurs H, Kerstjens HA, Gosens R.

Am J Respir Cell Mol Biol (2014 Apr) 50:690-8. Abstract/Full Text

Role of the M3 muscarinic acetylcholine receptor subtype in murine ophthalmic arteries after endothelial removal.

Gericke A, Steege A, Manicam C, Böhmer T, Wess J, Pfeiffer N.

Invest Ophthalmol Vis Sci (2014 Jan 29) 55:625-31. Abstract/Full Text

Muscarinic receptor subtype-specific effects on cigarette smoke-induced inflammation in mice.

Kistemaker LE, Bos IS, Hylkema MN, Nawijn MC, Hiemstra PS, Wess J, Meurs H, Kerstjens HA, Gosens R.

Eur Respir J (2013 Dec) 42:1677-88. Abstract/Full Text

Novel structural and functional insights into M3 muscarinic receptor dimer/oligomer formation.

Hu J, Hu K, Liu T, Stern MK, Mistry R, Challiss RA, Costanzi S, Wess J.

J Biol Chem (2013 Nov 29) 288:34777-90. Abstract/Full Text

A novel experimental strategy to assess the metabolic effects of selective activation of a G(q)-coupled receptor in hepatocytes in vivo.

Li JH, Jain S, McMillin SM, Cui Y, Gautam D, Sakamoto W, Lu H, Jou W, McGuinness OP, Gavrilova O, Wess J.

Endocrinology (2013 Oct) 154:3539-51. Abstract/Full Text

Muscarinic receptors as model targets and antitargets for structure-based ligand discovery.

Kruse AC, Weiss DR, Rossi M, Hu J, Hu K, Eitel K, Gmeiner P, Wess J, Kobilka BK, Shoichet BK.

Mol Pharmacol (2013 Oct) 84:528-40. Abstract/Full Text

Minireview: Novel aspects of M3 muscarinic receptor signaling in pancreatic β-cells.

Nakajima K, Jain S, Ruiz de Azua I, McMillin SM, Rossi M, Wess J.

Mol Endocrinol (2013 Aug) 27:1208-16. Abstract/Full Text

Direct-pathway striatal neurons regulate the retention of decision-making strategies.

Ferguson SM, Phillips PE, Roth BL, Wess J, Neumaier JF.

J Neurosci (2013 Jul 10) 33:11668-76. Abstract/Full Text

Novel designer receptors to probe GPCR signaling and physiology.

Wess J, Nakajima K, Jain S.

Trends Pharmacol Sci (2013 Jul) 34:385-92. Abstract/Full Text

A Gαs DREADD mouse for selective modulation of cAMP production in striatopallidal neurons.

Farrell MS, Pei Y, Wan Y, Yadav PN, Daigle TL, Urban DJ, Lee HM, Sciaky N, Simmons A, Nonneman RJ, Huang XP, Hufeisen SJ, Guettier JM, Moy SS, Wess J, Caron MG, Calakos N, Roth BL.

Neuropsychopharmacology (2013 Apr) 38:854-62. Abstract/Full Text