We are a highly enthusiastic research group in the field of cellular signaling, founded in 2021 at the Institute of Biochemistry, Romanian Academy, Bucharest, Romania.
Our mission is to study the role of membrane receptors in various physiological and pathophysiological models. The main research focus of the group is a family of membrane proteins called G-protein coupled receptors (GPCRs). Apart from the fundamental research on GPCR functions in the regulation of cellular functions, we are also actively pursuing research lines with translational potential.
An important feature of the GPCR superfamily is the presence in the human genome of a large number (around 150) of gpcr genes that encode for receptors with unknown biological functions, nicknamed “orphan receptors”. Since more than 30% of the globally-approved drugs target less than 10% of the GPCRome, it is reasonable to believe that the drug targets portfolio might include new members of receptors belonging to the orphan category, with previously unrecognized therapeutic potential.
It is therefore also the aim of the academic labs, such as ours, to invest considerable efforts in identifying the biological role of the oGPCRs (deorphanization). One of the first steps in the deorphanization process is the identification of the endogenous ligands that can modulate the activity of a target oGPCR. This allows the elucidation of the cellular pathways modulated by the quest receptor and can further provide valuable information regarding the biological role of the ligand//receptor pair.
Consistent with the role of GPCRs in modulating signaling pathways it is also important to understand the cellular context into which a certain GPCR operates. Therefore, we also aim to understand the functional interaction between GPCRs and other membrane proteins such as ion channels. It is known that a single cell may express around 20 to 50 GPCRs that are coexpressed with various ion channels and other membrane proteins. It is very interesting to find out the cross-talk between an activated GPCR and a coexpressed ion-channel; this, in turn, can lead to important findings regarding the integrative signaling pathways and the biological consequences.
Human metabolome contains more than 6000 metabolites that exert various biological functions. Many of them are well characterized and belong to important metabolic regulatory pathways. However, as in the case of the orphan receptors, there is a large number of metabolites with unknown biological effects, termed orphan metabolites. Circulating orphan metabolites might have biological effects through interaction with cognate receptors, known or unknown. The characterization of the cellular mechanism of action of the orphan metabolites is one of our major interests. We focus mainly on biologically active lipid metabolites, small molecules, and secreted peptides.
(under construction)
Ø Identification of novel modulators (agonists, antagonists, PAMs, and NAMs) of known- and orphan- GPCRs through high-throughput screening (HTS) of FDA-approved and custom-made small-molecule libraries. Characterization of cellular pathways modulated by the identified modulator/receptor pairs.
Ø Identification and characterization of the functional interaction between GPCRs, ion channels, and other poorly characterized proteins.
Ø Identification and characterization of the mechanism of action of novel secreted peptides/metabolites with “hormone-like actions”.
Ø Single-cell expression analysis of various known- and orphan- GPCRs in different tissues.
The projects pursued by the Cell Signaling Research Group, at the Institute of Biochemistry, Romanian Academy are generously supported through the following funding research grants:
1. Drug repurposing as a source of novel medication for type-2-diabetes (REPODRUG), PN-III-P2-2.1-PED-2019-5179 awarded by the UEFISCDI agency, implementation: 2020 - 2023, project director: Sorin Tunaru
2. Next generation of drug targets for schizophrenia (NEXTDRUG), EEA-RO-NO-2018-0535, awarded by UEFISCDI and Norway Research Agency, implementation: 2021-2023, project director: Sorin Tunaru
3. Identification and Characterization of the CART-Neuropeptide Receptor (CARTR), PN-III-P4-ID-PCE-2020-2411, awarded by the UEFISCDI agency, implementation: 2021-2023, project director: Sorin Tunaru
Scientific Researcher
Sorin Tunaru is a researcher in the Institute of Biochemistry of the Romanian Academy. Sorin is currently working in Cell Signaling Research in the Enzymology.
Research Scientist
Alexandra Bănică is a researcher in the Institute of Biochemistry of the Romanian Academy. Alexandra is currently working in Cell Signaling Research in the Enzymology.
Scientific Researcher
Born: 19th of November 1988, Ploiesti, Romania 2003 - 2007: „Ion Luca Caragiale” National College, Ploieşti, Romania 2007- 2012: Faculty of Pharmacy at University of Medicine and Pharmacy "Carol Davila" Buchare More...
Volunteer
Scientific Researcher
Rodica-Aura Badea is a researcher in the Institute of Biochemistry of the Romanian Academy. Rodica-Aura is currently working in Cell Signaling Research in the Enzymology.
1. Simmons JD, Peterson GJ, Campo M, Lohmiller J, Skerrett SJ, Tunaru S, Offermanns S, Sherman DR, Hawn TR.
Nicotinamide Limits Replication of Mycobacterium tuberculosis and Bacille Calmette-Guérin Within Macrophages.
J Infect Dis. 2020 Mar 2;221(6):989-999
2. Helker CSM, Mullapudi ST, Mueller LM, Preussner J, Tunaru S, Skog O, Kwon HB, Kreuder F, Lancman JJ, Bonnavion R, Dong PDS, Looso M, Offermanns S, Korsgren O, Spagnoli FM, Stainier DYR.
A whole organism small molecule screen identifies novel regulators of pancreatic endocrine development. Development. 2019 Jul 24;146(14)
3. Tunaru S, Bonnavion R, Brandenburger I, Preussner J, Thomas D, Scholich K, Offermanns S.
20-HETE promotes glucose-stimulated insulin secretion in an autocrine manner through FFAR1.
Nat Commun. 2018 Jan 12;9(1):177
4. Schmitz K, Brunkhorst R, de Bruin N, Mayer CA, Häussler A, Ferreiros N, Schiffmann S, Parnham MJ, Tunaru S, Chun J, Offermanns S, Foerch C, Scholich K, Vogt J, Wicker S, Lötsch J, Geisslinger G, Tegeder I.
Dysregulation of lysophosphatidic acids in multiple sclerosis and autoimmune encephalomyelitis.
Acta Neuropathol Commun. 2017 Jun 2;5(1):42
5. Hohmann SW, Angioni C, Tunaru S, Lee S, Woolf CJ, Offermanns S, Geisslinger G, Scholich K, Sisignano M.
The G2A receptor (GPR132) contributes to oxaliplatin-induced mechanical pain hypersensitivity.
Sci Rep. 2017 Mar 27;7(1):446.
6. Zinn S, Sisignano M, Kern K, Pierre S, Tunaru S, Jordan H, Suo J, Treutlein EM, Angioni C, Ferreiros N, Leffler A, DeBruin N, Offermanns S, Geisslinger G, Scholich K.
The leukotriene B4 receptors BLT1 and BLT2 form an antagonistic sensitizing system in peripheral sensory neurons.
J Biol Chem. 2017 Apr 14;292(15):6123-6134.
7. Tunaru S, Chennupati R, Nüsing RM, Offermanns S.
Arachidonic Acid Metabolite 19(S)-HETE Induces Vasorelaxation and Platelet Inhibition by Activating Prostacyclin (IP) Receptor.
PLoS One. 2016 Sep 23;11(9):e0163633.
8. Tang C, Ahmed K, Gille A, Lu S, Gröne HJ, Tunaru S, Offermanns S.
Loss of FFA2 and FFA3 increases insulin secretion and improves glucose tolerance in type 2 diabetes.
Nat Med. 2015 Feb;21(2):173-7.
9. Preuß B, Tunaru S, Henes J, Offermanns S., Klein R.
A novel luminescence-based method for the detection of functionally active antibodies to muscarinic acetylcholine receptors of the M3 type (mAchR3) in patients' sera.
Clin Exp Immunol. 2014 Jul;177(1):179-89. doi: 10.1111/cei.12324
10. Conzelmann M, Williams EA, Tunaru S, Randel N, Shahidi R, Asadulina A, Berger J, Offermanns S, Jékely G.
Conserved MIP receptor-ligand pair regulates Platynereis larval settlement. Proc Natl Acad Sci U S A. 2013 May 14;110(20):8224-9.
11. Tunaru S, Althoff TF, Nüsing RM, Diener M, Offermanns S.
Castor oil induces laxation and uterus contraction via ricinoleic acid activating prostaglandin EP3 receptors.
Proc Natl Acad Sci U S A. 2012 Jun 5;109(23):9179-84.
12. Lukasova M, Hanson J, Tunaru S, Offermanns S.
Nicotinic acid (niacin): new lipid-independent mechanisms of action and therapeutic potentials.
Trends Pharmacol Sci. 2011 Dec;32(12):700-7.
13. Hanson J, Gille A, Zwykiel S, Lukasova M, Clausen BE, Ahmed K, Tunaru S, Wirth A, Offermanns S.
Nicotinic acid- and monomethyl fumarate-induced flushing involves GPR109A expressed by keratinocytes and COX-2-dependent prostanoid formation in mice.
J Clin Invest. 2010 Aug;120(8):2910-9.
14. Ahmed K, Tunaru S, Tang C, Müller M, Gille A, Sassmann A, Hanson J, Offermanns S.
An autocrine lactate loop mediates insulin-dependent inhibition of lipolysis through GPR81. Cell Metab. 2010 Apr 7;11(4):311-9.
15. Ahmed K, Tunaru S, Offermanns S.
GPR109A, GPR109B and GPR81, a family of hydroxy-carboxylic acid receptors. Trends Pharmacol Sci. 2009 Nov;30(11):557-62.
16. Ahmed K, Tunaru S, Langhans CD, Hanson J, Michalski CW, Kölker S, Jones PM, Okun JG, Offermanns S.
Deorphanization of GPR109B as a receptor for the beta-oxidation intermediate 3-OH- octanoic acid and its role in the regulation of lipolysis.
J Biol Chem. 2009 Aug 14;284(33):21928-33.
17. Kero J, Ahmed K, Wettschureck N, Tunaru S, Wintermantel T, Greiner E, Schütz G, Offermanns S.
Thyrocyte-specific Gq/G11 deficiency impairs thyroid function and prevents goiter development.
J Clin Invest. 2007 Sep;117(9):2399-407.
18. Tunaru S, Lättig J, Kero J, Krause G, Offermanns S.
Characterization of determinants of ligand binding to the nicotinic acid receptor GPR109A (HM74A/PUMA-G).
Mol Pharmacol. 2005 Nov;68(5):1271-80.
19. Niedernberg A, Tunaru S, Blaukat A, Harris B, Kostenis E.
Comparative analysis of functional assays for characterization of agonist ligands at G protein- coupled receptors.
J Biomol Screen. 2003 Oct;8(5):500-10.
20. Niedernberg A, Tunaru S, Blaukat A, Ardati A, Kostenis E.
Sphingosine 1-phosphate and dioleoylphosphatidic acid are low affinity agonists for the orphan receptor GPR63.
Cell Signal. 2003 Apr;15(4):435-46.
21. Tunaru S, Kero J, Schaub A, Wufka C, Blaukat A, Pfeffer K, Offermanns S.
PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nat Med. 2003 Mar;9(3):352-5.
Romanian Academy