BrainMap

Andrei-Jose Petrescu

PhD

Senior Researcher, grade 1 - INSTITUTUL DE BIOCHIMIE

Researcher | Scientific reviewer | PhD supervisor

Head of the Department of Bioinformatics & Structural Biochemistry at the Institute of Biochemistry of Romanian Academy; PhD Supervisor at the School of Advanced Studies of the Romanian Academy; Vice-president of CNATDCU Pannel III - Biomedical Sciences; Member of the National Council for Scientific Research - Biology Commission

Web of Science ResearcherID: https://www.webofscience.com/wos/author/record/1369256

Curriculum Vitae (10/01/2023)

Expertise & keywords

Next generation of drugs targets for schizophrenia. Call name: EEA Grants - Proiecte Colaborative de Cercetare
EEA-RO-NO-2018-0535 2021 - 2024

Role in this project:

Coordinating institution: INSTITUTUL DE BIOCHIMIE

Project partners: INSTITUTUL DE BIOCHIMIE (RO); University of Oslo Faculty of Medicine Institute of Clinical Medicine (NO); INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO” (RO)

Affiliation:

Project website: https://nextdrug.eu/

Abstract:

Schizophrenia (SCZ) is 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 it 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 poor knowledge 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 the Norwegian partner's 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 next 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 methods 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 identified ligand/receptor pairs in brain physiology and also in SCZ pathology.

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

Identification of new molecules involved in melanoma associated antigens production Call name: P 1 - SP 1.1 - Proiecte de cercetare Postdoctorală
PN-III-P1-1.1-PD-2019-1278 2020 - 2022

Role in this project:

Coordinating institution: INSTITUTUL DE BIOCHIMIE

Project partners: INSTITUTUL DE BIOCHIMIE (RO)

Affiliation: INSTITUTUL DE BIOCHIMIE (RO)

Project website: https://gabrielachiritoiu.wixsite.com/pd183

Abstract:

In the last decades cancer immunotherapy has gained remarkable attention with improved patient’s outcome. However, some tumors develop resistance and the treatment becomes inefficient. Usually, tumor resistance is caused by down regulation of the antigens presentation to the cell surface, which allows tumor cells to become “invisible” and escape from cytotoxic T cells attack. By restoring antigens presentation pathway, the tumor cells become visible to the immune system and allow efficient T cells recognition and tumor clearance. Antigens presenting machinery relies on key processes such as: antigenic peptides production, processing and (Major Histocompatibility Complex) MHC class I loading. In this project we will develop a model of melanoma cells able to display an increased amount of antigenic peptides to the cell surface and will also perform screening experiments for identification of new melanoma epitopes. Using a melanoma model cell line we aim to target for the first time three key processes of the antigen presentation pathway by the following strategies: 1) selection of the antigens for degradation by CRISPR activation of Endoplasmic Reticulum Associated Degradation (ERAD) components, 2) modulating proteases activity for enhancing cytosolic production of the antigens and 3) activation of MHC class I presentation promoter in parallel with diverting antigen presentation to the endocytic-recycling pathway. These strategies should result in increased antigens presentation diversity at the melanoma cells surface and identification of new melanoma antigens. Discovery of new antigens may have crucial clinical relevance since it was shown that efficacy of PD1/PDL-1 therapy is improved when immunity was previously boosted and that combination of immunotherapy with chemo/radiotherapy gives best clinical outcome.

From the classical nutrition to precise nutrition in animal production, scientific basis for the nutrition security of the population Call name: P 1 - SP 1.2 - Proiecte complexe realizate in consorții CDI
PN-III-P1-1.2-PCCDI-2017-0473 2018 - 2021

Role in this project:

Coordinating institution: INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE PENTRU BIOLOGIE SI NUTRITIE ANIMALA - IBNA BALOTESTI

Project partners: INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE PENTRU BIOLOGIE SI NUTRITIE ANIMALA - IBNA BALOTESTI (RO); UNIVERSITATEA BUCURESTI (RO); UNIVERSITATEA BABES BOLYAI (RO); INSTITUTUL DE BIOCHIMIE (RO); UNIVERSITATEA "ŞTEFAN CEL MARE" DIN SUCEAVA (RO); UNIVERSITATEA DE STIINTE AGRICOLE SI MEDICINA VETERINARA CLUJ-NAPOCA (RO)

Affiliation:

Project website: http://www.ibna.ro/proiecte-de-cercetare/item/110-pn-iii-p1-1-2-pccdi-2017-0473

Abstract:

The overall objective of the project is to strengthen the institutional capacity of IBNA by developing new research directions based on „omics” technologies – nutrigenomics, toxicogenomics, proteomics, metabolomics – and to relaunch the Laboratory of Biotechnology. This will generate a set of innovative outcomes in animal nutrition. The innovative aspects of the project include: use of agro-food wastes as adsorption and detoxifying agents for feed contaminants; testing the effect of phytoadditives (plants or plant extracts not yet used for such purposes) as antibiotic replacers (willow bark extracts) on the interaction between the intestinal tract physiology and the intestinal microflora; investigation of several less characterized and used protein-oleaginous sources (cowpea, Jerusalem artichoke, etc.); in vitro experimental models to evaluate the decontaminating potential of wastes under conditions of concurrent fungal, viral and microbial contamination; development of new feeding products which ensure a more efficient use of the protein in ruminants.

The project covers three regions of development and the partners are prestigious institutions, with complementary infrastructure and expertise, with converging scientific interests. The consolidation of new directions will enhance, both for IBNA (the relaunched institution), and for its partners, their capacity of applying for/running research projects, allowing studies with a high level of complexity, which generate practical results, relevant for the development of the animal production sector.

The project will impact on the human resources, the budget allowing the employment of 14 researchers (of which 10 by IBNA), whose specialisation is already ensured; it will also support the enhancement of the scientific expertise of the senior researchers by using vouchers. The training periods will enrich the portfolio of methods and techniques that can be applied for the directions in which IBNA aims to develop/relaunch.

Development of advanced platforms for the analysis and modeling of complex biological systems Call name: P 1 - SP 1.2 - Proiecte complexe realizate in consorții CDI
PN-III-P1-1.2-PCCDI-2017-0046 2018 - 2021

Role in this project:

Coordinating institution: INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE PENTRU ELECTROCHIMIE SI MATERIE CONDENSATA - INCEMC TIMISOARA

Project partners: INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE PENTRU ELECTROCHIMIE SI MATERIE CONDENSATA - INCEMC TIMISOARA (RO); INSTITUTUL DE BIOCHIMIE (RO); UNIVERSITATEA DE STIINTE AGRICOLE SI MEDICINA VETERINARA CLUJ-NAPOCA (RO); INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE CHIMICO - FARMACEUTICA - I.C.C.F. BUCURESTI (RO)

Affiliation: INSTITUTUL DE BIOCHIMIE (RO)

Project website: https://www.incemc.ro/index.php?page=AZ/PN-III-P1-1.2-PCCDI-2017-0046.html

Abstract:

The complex project 'Development of advanced platforms for the analysis and modeling of complex biological systems' (TEHNOBIOSIST) coordinated by INCEMC Timisoara, in collaboration with IBAR Bucuresti, USAMV Cluj-Napoca and ICCF Bucuresti consists of 3 projects with the following objectives: 1. designing and functionalization of a bioanalytical platform in multiplex system for microfluidics-mass spectrometry coupling and its applications in modern glycoproteomics; 2. development of proteomic methods employing microfluidic and bioinformatic technologies for pharmacological assays; 3. implementation of these advanced systems for authenticity and quality assessment of Romanian vegetal oils.

The platforms designed within TEHNOBIOSIST will provide a major technical-economical and bioeconomical input derived from: i) complete automatization; ii) reducing the working time, sample consumption and analysis costs; iii) increase in the reproducibility, sensitivity of the experiment and accuracy of generated data; iv) development and updating of the existing databases with the newly identified biomarkers.

By the foreseen results, TEHNOBIOSIST has a marked bioeconomical impact: innovation in the analytical field which will enhance a thorough study of complex biological systems; hiring of young researchers; reorganization of R&D national system on modern and high performance bases; innovation, development and upgrading of the research infrastructure existing at the institutions involved in the project and last, but not least, providing (after patenting/publication) the pharmaceutical companies, the analytical system producers, bioclinical laboratories and the economical agents in charge with the control of food product quality with new and efficient techniques, optimized for a broad range of analyses and of new scientific results based on which they can focus their activity, their own research and production in the sense of improving the quality of life and products in Romania.

Structure assisted investigation of critical protein families involved in plant immunity Call name: P 4 - Proiecte de Cercetare Exploratorie
PN-III-P4-ID-PCE-2016-0650 2017 - 2019

Role in this project:

Coordinating institution: INSTITUTUL DE BIOCHIMIE

Project partners: INSTITUTUL DE BIOCHIMIE (RO)

Affiliation: INSTITUTUL DE BIOCHIMIE (RO)

Project website: http://www.biochim.ro/grant-7-strassist/

Abstract:

We aim by this proposal to build up upon our previous experience in tackling new aspects related to the molecular structure, interactions and functioning of two major protein classes of plant immune system: the R-gene products and the constitutive tandems formed as a first layer of plant immunity in tomato by cell surface receptor-like kinases (RLKs) and receptor like proteins (RLPs), in an attempt to understanding their functioning.

Related to R-proteins we intend to further build upon results obtained on the structure of CC-, NB- and LRR- domains and their interactions, by addressing new problems, such as: (1) The quantification of LRR domain structural diversity of 130 R proteins we have recently identified in the potato genome in collaboration with Aska Goverse from Wageningen University, member of the Potato Genome Consortium. (2) The investigation of the structural basis of CC domain interactions in RGA4 and RGA5 R-protein families from rice by combining molecular modeling and simulation with crystallography, NMR and yeast-two hybrid, in collaboration with the group of Thomas Kroj form INRA Montpellier. (3) And finally the investigation of interactions taking place in the complexes formed by Arabidopsis ZAR1, ZED1 with the AVR HopZ1a by combining bioinformatics, molecular modelling and laboratory experiments, in collaboration with the group of Jennifer Lewis from Berkeley University.

Related to RLK-RPS, the first layer of plant immunity - we intend to combine our experience in glycobiology and biocomputing in aiming to investigate the glycosylation of tomato Cf4/9 and model its constitutive interactions with SOBIR1, the suppressor of BIR1 RLK, in collaboration with Matthieu Joosten from the Laboratory of Phytopathology from Wageningen.

Screening and developing of a novel family of natural and synthetic HIV Integrase inhibitors Call name: P 3 - SP 3.2 - Proiecte ERA.NET
HIVERA-INIRAGI 2016 - 2019

Role in this project:

Coordinating institution: SPITALUL CLINIC "COLENTINA" BUCURESTI

Project partners: SPITALUL CLINIC "COLENTINA" BUCURESTI (RO); INSTITUTUL DE BIOCHIMIE (RO)

Affiliation: INSTITUTUL DE BIOCHIMIE (RO)

Project website: http://www.cdpcolentina.ro/proiecte/virusul_imunodeficientei_umane/index_en.htm

Abstract:

Immediately after birth and within the first months after that newborn infants from HIV infected mothers have to be subjected to prophylactic treatment to prevent viral infection. HIV Integrase(IN) is the enzyme that mediates the viral

genome integration into the Th host cells chromosomes and its catalytic prevention represents a major way to stop the viral infection. Because HIV-IN resembles in its structure and reaction mechanism to RAG1 protein, which assembles the lymphocytes antigen receptor genes, the treatment with IN inhibitors(INi) in newborns interferes with the ability of treated patients to develop a normal immune response. The major goal of our proposal is to find and test new HIV specific INi chemical scaffolds of natural origin which do not interfere with RAG somatic recombination. We propose to develop rapid, low cost, efficient FRET screening assays. With them we will HTP screen first a library of natural compounds(NP) of herbal origin. Informed by the best selected NPs we will in silico design and synthesize a derivatized set of HIV-INi compounds

which will be again screened in vitro for dual HIV Integrase inhibition and RAG non interference effects. The uniquely discovered lead compounds will also be tested in immune

B cell progression assays and for their antiretroviral potency on HIV infected T cells.

Design and testing of a new family of specific drug HIV Integrase inhibitors which do not interfere with V(D)J recombination Call name: Joint Applied Research Projects - PCCA 2013 - call
PN-II-PT-PCCA-2013-4-0930 2014 - 2017

Role in this project:

Coordinating institution: SPITALUL CLINIC "COLENTINA" BUCURESTI

Project partners: SPITALUL CLINIC "COLENTINA" BUCURESTI (RO); APEL LASER S.R.L. (RO); INSTITUTUL DE BIOCHIMIE (RO); INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH (RO)

Affiliation:

Project website: http://www.apellaser.com/hivinvdj/

Abstract:

After birth newborn infants from HIV (Human Immunodeficiency Virus) infected mothers have to be subjected to prophylactic treatment against viral infection. HIV Integrase is the enzyme that mediates the integration of the viral genome into the host cells chromosomes and its catalytic prevention represents a major way to stop the viral infection. Despite its major clinical advantages (low toxicity compared to nucleotide analogs, lower effective IC50 and fewer adverse reactions than most protease inhibitors), the treatment with HIV Integrase inhibitors(INi) in newborns induces a paradoxical situation. Because HIV-IN resembles in its structure and reaction mechanism to Recombination Activating Gene protein RAG1, which assembles the lymphocytes antigen receptors, INi medication interferes with the ability of treated patients to develop a normal immune response. By reducing RAG activity (Melek, 2002), the currently used HIV-INi induce an iatrogenic immunodeficiency which mimics the onset of AIDS (acquired immune deficiency syndrome). This situation sometimes prompts at these treated patients a more aggressive therapy with higher medication doses, which in turn accentuates the aforementioned immunodeficiency. We propose to solve the major drawback of INi treatment that it cannot be addressed to newborns exposed to high risk acquiring HIV-1(type1) infections.The major goal of our proposal is to test new HIV specific Integrase inhibitory compounds which do not interfere with RAG somatic recombination. Our expertise with biophysical assays testing RAG activity is the key element ensuring the creativity and originality of this proposal. We propose to use a new strategy to separately screen for compounds inhibiting IN at each of its three integration steps: viral DNA-IN binding, catalytic 3' DNA nicking and strand Transfer. Nowadays, in drug discovery and screening strategies just one of these IN activities is targeted for potential inhibition. Based upon our results from our work investigating critical RAG-DNA binding/bending activity(Ciubotaru et. al, 2003, 2013) in somatic recombination, we propose to develop rapid, low cost, efficient fluorescence resonance energy transfer (FRET) setups and screening assays some at single molecule level. With them we will high-throughput screen(HTPS) our in silico designed and derivatized library of HIV Integrase inhibitory compounds for their in vitro dual HIV Integrase inhibition and RAG activity interference effects. Dual screening for IN inhibition with no RAG activity interference is unprecedented and represents an entirely original approach for the development of this family of drugs. The FRET in vitro screened compounds will be quantitatively tested for their effect on RAG mediated DNA substrate cleavage reactions. The lead compounds will then be tested in a primary cell line culture screening assay. We will test their cell toxicity and their potential inhibitory effect on stage progression from pre B to immature B lymphocyte(which requires somatic recombination). This will be assessed by cell survival and preB/IgM surface markers display. The best candidate compounds screened by our assays will be further tested for their potential to interfere with antigen activation of B cells from biopsies of immunocompromised lymphoma patients. For this, the compounds will be added on lymphomatous B cells cultures with LPS (Gram Negative Bacterial Lipopolysaccharide) and Interleukin 4 (IL4) and their effect tested by proliferation tests directed against control cell cultures without drugs. Our selected lead compounds should not affect patients immunity, hence after future tests in animals and in patient clinical trial studies they should reach the highest marketing potential among all other drugs from their class.

Modeling molecular complexes and assemblies with experimental and bioinformatic constraints Call name: Exploratory Research Projects - PCE-2011 call
PN-II-ID-PCE-2011-3-0342 2011 - 2016

Role in this project:

Coordinating institution: Institutul de Biochimie al Academiei Romane

Project partners: Institutul de Biochimie al Academiei Romane (RO)

Affiliation: Institutul de Biochimie al Academiei Romane (RO)

Project website: http://www.biochim.ro/ib/projects/molint/molint_e.php

Abstract:

Protein-protein and protein-DNA assembiles in three types of systems will be investigated by constrained molecular modeling and simulation, aiming to assist and drive experimental research within the particular fields explored. The first field relates to the domain architecture of resistance gene products in plants and their interaction with effector proteins, an interaction that is instrumental in plant pathogen defense mechanisms. The second explores the structural basis of the differential functioning of human topoisomerases and the effects of some point mutations proven to induce differential malignant effects in topo II alpha and beta. Finally the third line of research tackles the structural biology of RAG-DNA synaptic complexes, involved in the assembly of the gene segments coding for the variable portions of lymphocyte antigen receptors. The three directions reflect the diversity of macromolecular assemblage in biological systems but also unveil common roots residing in the molecular geometry, interactions and dynamics at atomic level, and hence they can be tackled by common approach in which we intend to bring some contributions. On this line we intend to continue the endeavor started in a previous PN2-ID project to develop and implement in-silico techniques and use them as a motive force in molecular life sciences, when intertwined with the experimental approach.

Engineering Yeast and Plants for Heavy Metal Applications: from Bioremediation to Bioextraction Call name: EEA Research Programme under EEA Financial Mechanism 2009-2014
EEA-JRP-RO-NO-2013-1-0047 2013 -

Role in this project:

Coordinating institution: UNIVERSITATEA BUCURESTI

Project partners: UNIVERSITATEA BUCURESTI (RO); Norwegian University of Science and Technology (NO); INSTITUTUL DE BIOCHIMIE (RO)

Affiliation:

Project website:

Abstract:

Trace elements (Co, Cu, Fe, Mn, Ni, Zn) have been in the prime light of basic and applied research due to their dualistic action upon living organisms, being necessary in minute amounts for the normal metabolism but getting toxic when present in concentrations higher than the physiological levels. As such, the heavy metal pollution represents a threat to water supplies, agriculture soils, human and animal health, whereas the deficiency is considered equally deleterious for any form of life, or for important human activities, such as agriculture.

In this project we aim to use molecular and bioinformatics approaches to engineer yeast and plants designed to hyperaccumulate heavy metals without interfering with the normal metabolism. In addition we aim to establish the applicability of such organisms to various heavy metal-related biotechnologies, such as soil and water bioremediation, bioextraction, metal restriction to plant organs, metal-enriched food supplements, improved imaging techniques, etc.

The project will imply systemic investigations of an array of metal ions against a series of recombinant proteins and synthetic peptides designed for each metal and expressed differentially in yeast and plants. The proposed work is interdisciplinary, combining in silico screening, molecular biology, bioinorganic chemistry, genetics and bioinformatics, aiming to provide an unprecedented coverage of the metal-protein/peptide interaction by facilitating the analysis of synergistic and antagonistic relationship between cell components and metal-related metabolism.

This project will be carried out by a consortium of three partner groups with relevant research and innovation expertise: University of Bucharest (Romania, Project Promoter, PP), University of Science and Technology from Trondheim (Norway, Partner One, P1), and Institute of Biochemistry of the Romanian Academy (Romania, Partner Two, P2).The consortium was established based on the state-of-the-art infrastructure already existing in the implementing institutions and on the strong complementarities between the research expertise of the partner groups. The project’s output is expected to have impact on the thematic area Environmental protection and management.

FILE DESCRIPTION	DOCUMENT
List of research grants as project coordinator
List of research grants as partner team leader
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