BrainMap

Mr. Sorin Tunaru

Dr.

Senior Scientist/CSII/Group Leader - INSTITUTUL DE BIOCHIMIE

Other affiliations

Project leader - Max Planck Institute for Heart and Lung Research (Germany)

Researcher

Curriculum Vitae (26/02/2024)

Expertise & keywords

Next generation of drugs targets for schizophrenia. Call name:
EEA-RO-NO-2018-0535 2021 - 2023

Role in this project:

Coordinating institution: INSTITUTUL DE BIOCHIMIE

Project partners: INSTITUTUL DE BIOCHIMIE (); University of Oslo Faculty af Medicine Institute of Clinical Medicine (); INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO” ()

Affiliation: INSTITUTUL DE BIOCHIMIE ()

Project website:

Abstract:

Next Generation of Drug Targets for Schizophrenia

Schizophrenia (SCZ) is a one of the worst debilitating psychotic mental disorder affecting almost 1% of the human population. SCZ is a very complex syndrome with a heterogeneous etiology and is diagnosed in terms of positive (e.g. hallucinations), negative (such as social withdrawal) and cognitive symptoms (IQ deterioration). The treatments used for SCZ have severe limitations, being efficient for only 50% of the patients. In addition, the current treatments involve severe neurological and metabolic side effects. The main reason for the insufficient effectiveness of current SCZ medication is the lack of alternative targets due to a poor knwoledge of the molecular origins of SCZ. Therefore, there is an urgent need to identify novel molecular targets implicated in SCZ onset and development. Our joint project proposal aims to use an unprecedented level of interdisciplinarity, by combining concepts and techniques of genomics, proteomics, metabolomics, pharmacology, drug discovery and mouse genetics to identify novel molecular mechanisms in SCZ with potential translation as therapeutic targets. The present research proposal takes advantage of Norwegian partner outstanding expertise in transcriptomics and genome-wide association studies (GWAS) and of the Romanian partners expertise in proteomics, pharmacology, drug discovery and animal genetics to identify nex generation of drug targets for SCZ.

Our preliminary results indicate the existence of previously not described risk genes encoding proteins belonging to the superfamily of G-protein coupled receptors (GPCRs). The identified GPCR genes encode three receptor proteins (GPR27, GPR75 and GPR173) with unknown endogenous ligands and functions, generically known as orphan GPCRs (oGPCRs). Importantly, these three receptors are expressed in relevant brain areas known to be involved in SCZ. Remarkably, quantitative transcriptomics revealed that all three oGPCRs are significantly downregulated in SCZ patients.

Using state-of-the-art methodos of cellular biology as well as reverse pharmacology technologies, we will initially identify endogenous ligands and compounds with modulatory activity for each receptor. In this way, we aim to understand GPR27, GPR75 and GPR173 roles in neuronal function as well as potential implications in SCZ. Following the identification of endogenous ligands and modulatory compounds, we aim to discover endogenously expressed intracellular proteins involved in receptor desensitization such as phosphorylating (protein kinases) and dephosphorylating proteins (protein phosphatases).

Finally, by using advanced mouse genetics, we plan to investigate the role of the identifed ligand/receptor pairs in brain physiology and also in SCZ pathology.

We expect that by identifying the biological roles of these receptors to open a new line of research from which both academia and pharma industry will profit with the final aim to deliver better therapeutics for patients suffering from this horrendous disease.

IDENTIFICATION AND CHARACTERIZATION OF THE CART NEUROPEPTIDE RECEPTOR Call name:
PN-III-P4-ID-PCE-2020-2411 2021 - 2023

Role in this project: Project coordinator

Coordinating institution: INSTITUTUL DE BIOCHIMIE

Project partners: INSTITUTUL DE BIOCHIMIE ()

Affiliation: INSTITUTUL DE BIOCHIMIE ()

Project website:

Abstract:

The energy balance of all organisms is controlled by the coordinated action of endogenous factors that influence the feeding behavior. These factors are either orexigenic (promoting food-seeking beahavior) or anorexigenic (contributing to satiety). Among these factors, orexigenic and anorexigenic neuropetides are essential in ensuring the proper response of organisms to challenging environmental conditions when food availability can be scarce. Cocaine- and amphetamine-regulated transcript (CART) was discovered in individuals with acute cocaine or amphetamine intoxication. This transcript encodes for several CART peptides with profound biological activity. Early studies demonstrated that CART peptides induce strong anorexigenic effects mimicking the effect of cocaine and amphetamines. Moreover, CART peptides are described as having significant effect in depression and anxiety. Despite all of the evidences that CART peptides are novel neurotransmitters, the identification of the receptor mediating these effects remained unsuccessful. In this proposal we aim to discover and fully characterize the long-sought CART peptides receptor, by using a combination of reverse and forward pharmacology strategies, entailing state-of-the art molecular biology, cellular pharmacology and protein biochemistry techniques. The identified receptor will also be subject to screening an FDA-approved drug library to discover modulators of its activity.

Drug repurposing as a source of novel medication for type-2-diabetes Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2019-5179 2020 - 2022

Role in this project: Project coordinator

Coordinating institution: INSTITUTUL DE BIOCHIMIE

Project partners: INSTITUTUL DE BIOCHIMIE (RO); UNIVERSITATEA BUCURESTI (RO)

Affiliation: INSTITUTUL DE BIOCHIMIE (RO)

Project website: https://sorintunaru.wixsite.com/repodrug

Abstract:

Type 2 diabetes (T2D) is a major global health problem, with increasing costs associated with the therapeutic strategies. In the treatment of T2D, a number of drugs are used, including metformin and sulphonylureas. Despite of the fact that nearly 10% of the world's population is affected by the T2D, there are a limited number of therapeutic solutions. G-protein coupled receptors (GPCRs) represent the largest super-family of membrane receptors and a successful drug target. More than 30% of FDA-approved drugs target this class of receptors. Within the GPCR superfamily there is a family of receptors that mediates the biological effects of dietary fatty acids. It is called the free-fatty acid receptor family (abbreviated as FFAR) and is composed of four members: FFAR1, FFAR2, FFAR3 and FFAR4. Of these, FFAR1 and FFAR4 stimulate glucose-induced insulin secretion (GSIS), either directly, due to expression in beta-pancreatic cells (such as FFAR1) or indirectly by stimulating incretin production (FFAR4). These receptors are endogenously activated by dietary fatty acids from the omega-3 and omega-6 series and are considered emerging T2D therapeutic targets. With all the efforts of pharma companies, to date no new drugs, targeting FFAR1 or FFAR4, have been developed until the final approval stage. In this project, we propose the identification of specific agonists of FFAR1 and FFAR4 by functional analysis of the drugs already approved by the FDA, by a process called drug repositioning. The success of this project would have major therapeutic implications because the drugs already approved by the FDA have well-studied pharmacokinetic and pharmacodynamic characteristics, facilitating their use in the treatment of T2D.

FILE DESCRIPTION	DOCUMENT
List of research grants as project coordinator or partner team leader
Significant R&D projects for enterprises, as project manager
R&D activities in enterprises
Peer-review activity for international programs/projects