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 Add to Contacts

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Publications

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

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Activation of G(12)-type G proteins in pancreatic β cells protects against impaired glucose homeostasis.

Pittala S, Liu L, Haspula D, Cui Y, Fulgenzi G, Inoue A, Wess J.

Sci Adv (2026 Aug 28) 12:eaeh5504. Abstract/Full Text

Altered G(i) signaling in enteroendocrine K cells in vivo causes pronounced changes in glucose homeostasis.

Rivera-Gonzalez O, Liu L, Gribble FM, Reimann F, Wess J.

Sci Adv (2026 Jul 31) 12:eaeb9805. Abstract/Full Text

G proteins of the G(12) family expressed by POMC neurons regulate key metabolic functions.

Haspula D, Cui Z, Pittala S, Cui Y, Lu H, Xiong Y, Jin J, Gavrilova O, Hwang E, Ajwani J, Portillo B, Williams KW, Inoue A, Wess J.

Sci Adv (2025 Jul 11) 11:eadu1670. Abstract/Full Text

Intra-islet α-cell Gs signaling promotes glucagon release.

Liu L, El K, Dattaroy D, Barella LF, Cui Y, Gray SM, Guedikian C, Chen M, Weinstein LS, Knuth E, Jin E, Merrins MJ, Roman J, Kaestner KH, Doliba N, Campbell JE, Wess J.

Nat Commun (2024 Jun 15) 15:5129. Abstract/Full Text

Activation of Gs signaling in mouse enteroendocrine K cells greatly improves obesity- and diabetes-related metabolic deficits.

Oteng AB, Liu L, Cui Y, Gavrilova O, Lu H, Chen M, Weinstein LS, Campbell JE, Lewis JE, Gribble FM, Reimann F, Wess J.

J Clin Invest (2024 Oct 22) 134. Abstract/Full Text

Additional Publications

G(12/13)-mediated signaling stimulates hepatic glucose production and has a major impact on whole body glucose homeostasis.

Pittala S, Haspula D, Cui Y, Yang WM, Kim YB, Davis RJ, Wing A, Rotman Y, McGuinness OP, Inoue A, Wess J.

Nat Commun (2024 Nov 19) 15:9996. Abstract/Full Text

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

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

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

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

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

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