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.
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