Arbeitsgruppe Thor

 

Dr. Doreen Thor
E-Mail: Diese E-Mail-Adresse ist vor Spambots geschützt! Zur Anzeige muss JavaScript eingeschaltet sein!

Telefon: +49 (0)341 97 22 177
Telefax: +49 (0)341 97 22 159

 

Arbeitsgruppe Thor

 

Dr. Doreen Thor
E-Mail: Diese E-Mail-Adresse ist vor Spambots geschützt! Zur Anzeige muss JavaScript eingeschaltet sein!

Telefon: +49 (0)341 97 22 177
Telefax: +49 (0)341 97 22 159

 

Overview

G protein-signaling pathways are involved in almost all physiological functions including the modulation and regulation of metabolic functions. With obesity and related diseases like diabetes reaching epidemic proportions, an in-depth understanding of the regulatory processes will help to intervene with metabolic dysfunctions.

 

  

Research

The role of G protein-signaling pathways in physiological processes
G protein-coupled receptors (GPCR) comprise the largest family of transmembrane receptors and their signaling pathways are involved in a variety of physiological functions. However, analyzing the effect of a single GPCR in a specific tissue in vivo is nearly impossible because many GPCRs belong to families of related receptors and become activated by similar ligands. The presence of the endogenous agonist and the distribution of the desired receptor in different tissues further complicate the study. To overcome those limitations, receptors with newly designed abilities were developed. These receptors, so-called Designer Receptors Exclusively Activated by Designer Drug (DREADD), do not respond to their endogenous ligand but to otherwise pharmacological inert substances. Using transgenic animal models, DREADDs can help to decipher the impact of a single G protein pathway in specific tissues.

 

  

The relevance of Adhesion GPCRs in glucose and energy homeostasis
It is well established that G protein-signaling pathways regulate pancreatic islet and adipocyte function. However, the family of Adhesion GPCR (aGPCR) is not well characterized in this context although expression analysis revealed high frequency for several receptors of this family. Therefore, we are analyzing the contribution of aGPCRs in adipose tissue, pancreatic islet, and hepatocyte function. We are using cell culture and animal models to study the role of receptor activation and knock-down / knock-out on specific metabolic functions.

 

Team

  • Dr. Doreen Thor (Group Leader)
  • Isabell Kaczmarek (PhD student)
  • Juliane Röthe (PhD student)
  • Christian Zieschang (MD student)
  • Lea Fitze (Undergraduate)

  

Publications

Peer-reviewed Publications

  1. Jacobson KA, Delicado EG, Gachet C, Kennedy C, von Kügelgen I, Li B, Miras-Portugal MT, Novak I, Schöneberg T, Perez-Sen R, Thor D, Wu B, Yang Z, Müller CE.Update of P2Y receptor pharmacology: IUPHAR Review 27. Br J Pharmacol. 2020. doi: 10.1111/bph.15005. [Epub ahead of print].

  2. Röthe J, Kraft R, Schöneberg T, Thor D.
    Exploring G Protein-Coupled Receptor Signaling in Primary Pancreatic Islets. Biol Proced Online. 2020; 22: 4.

  3. Schöneberg T, Perez-Sen R, Thor D, Wu B, Yang Z, Müller CE. Update of P2Y receptor pharmacology: IUPHAR Review 27. Br J Pharmacol. 2020 Feb 9. doi: 10.1111/bph.15005. [Epub ahead of print].

  4. Suchý T, Zieschang C, Popkova Y, Kaczmarek I, Weiner J, Liebing AD, Çakir MV, Landgraf K, Gericke M, Pospisilik JA, Körner A, Heiker JT, Dannenberger D, Schiller J, Schöneberg TLiebscher I, Thor D. The repertoire of Adhesion G protein-coupled receptors in adipocytes and their functional relevance. Int J Obes (Lond). 2020. doi: 10.1038/s41366-020-0570-2. [Epub ahead of print]

  5. Knierim AB, Röthe J, Çakir MV, Lede V, Wilde C, Liebscher I, Thor D, Schöneberg T (2019). Genetic basis of functional variability in adhesion G protein-coupled receptors. Sci Rep.9:11036.

  6. Morgan RK, Anderson GR, Araç D, Aust G, Balenga N, Boucard A, Bridges JP, Engel FB, Formstone CJ, Glitsch MD, Gray RS, Hall RA, Hsiao CC, Kim HY, Knierim AB, Kusuluri DK, Leon K, Liebscher I, Piao X, Prömel S, Scholz N, Srivastava S, Thor D, Tolias KF, Ushkaryov YA, Vallon M, Van Meir EG, Vanhollebeke B, Wolfrum U, Wright KM, Monk KR, Mogha A (2019). The expanding functional roles and signaling mechanisms of adhesion G protein-coupled receptors. Ann N Y Acad Sci.

  7. Röthe J*, Thor D*, Winkler J, Knierim AB, Binder C, Huth S, Kraft R, Rothemund S, Schöneberg T, Prömel S (2019). Involvement of the Adhesion GPCRs Latrophilins in the Regulation of Insulin Release. Cell Rep. 26:1573-1584. (* shared contribution)

  8. Le Duc D, Schulz A, Lede V, Schulze A, Thor D, Brüser A, Schöneberg T (2017). P2Y Receptors in Immune Response and Inflammation. Adv Immunol. 136:85-121.

  9. Prömel S, Fiedler F, Binder C, Winkler, J, Schöneberg T, Thor D (2016). Deciphering and modulating G protein signalling in C. elegans using the DREADD technology. Sci Rep. 6: 28901.

  10. Cöster M, Wittkopf D, Kreuchwig A, Kleinau G, Thor D, Krause G, Schöneberg T (2012). Using ortholog sequence data to predict the functional relevance of mutations in G-protein-coupled receptors. FASEB J. 26:3273-81.

  11. Hu J, Thor D, Zhou Y, Wang Y, McMillin SM, Liu T, Mistry R, Challiss RAJ, Costanzi S, Wess J (2011). Structural aspects of M3 muscarinic acetylcholine receptor dimer formation and activation. FASEB J. 26:604-16.

  12. Liebscher I, Müller U, Teupser D, Engemaier E, Engel KM, Ritscher L, Thor D, Sangkuhl K, Ricken A, Wurm A, Piehler D, Schmutzler S, Fuhrmann H, Albert FW, Reichenbach A, Thiery J, Schöneberg T, Schulz A (2011). Altered immune response in mice deficient for the G protein-coupled receptor GPR34. J Biol Chem. 286:2101-10.

  13. Thor D, Le Duc D, Strotmann R, Schöneberg T (2009). Luciferase activity under ligand-dependent control of a G protein-coupled receptor. BMC Biotechnol. 9:46.

  14. Böselt I, Römpler H, Hermsdorf T, Thor D, Busch W, Schulz A, Schöneberg T (2009). Involvement of the V2 vasopressin receptor in adaptation to limited water supply. PLoS ONE 4:e5573.

  15. Thor D, Schulz A, Hermsdorf T, Schöneberg T (2008). Generation of an agonistic binding site for blockers of the M3 muscarinic acetylcholine receptor. Biochem J. 412:103-12.

  16. Römpler H, Stäubert C, Thor D, Schulz A, Hofreiter M, Schöneberg T (2007). G Protein-Coupled Time Travel: Evolutionary Aspects of GPCR Research. Mol Interv 1:17-25.

  17. Schöneberg T, Hermsdorf T, Engemaier E, Engel K, Liebscher I, Thor D, Zierau K, Römpler H, Schulz A (2007). Structural and functional evolution of the P2Y12-like receptor group. Purinergic Signal 3:255-268.

  18. Schulz A, Römpler H, Mitschke D, Thor D, Schliebe N, Hermsdorf T, Strotmann R, Sangkuhl K, Schöneberg T (2006). Molecular basis and clinical features of nephrogenic diabetes insipidus. Expert Review of Endocrinology & Metabolism 1:727-741.