BrainMap

Mrs. Stefana-Maria Petrescu

PhD

Senior Researcher, Director - INSTITUTUL DE BIOCHIMIE

Researcher | Scientific reviewer | Manager | PhD supervisor

Dr. Petrescu graduated from the Department of Biochemistry, University of Bucharest and obtained a PhD in Biology from the Romanian Academy. She was a DAAD fellow and FEBS fellowship recipient at University of Wurzburg, Germany, during 1990. She followed postdoctoral studies in the Department of Biochemistry at the University of Oxford, UK. She obtained three consecutive Wellcome Trust Grants in collaboration with the University of Oxford from 1995- 2004. She contributed to the understanding of the folding and degradation pathways regulating protein synthesis and maturation within the endoplasmic reticulum of mammalian cells. Dr. Petrescu has been granted the Award Emil Racovita of the Romanian Academy for the work on tyrosinase folding in 2002. She served as a member of the ERC panel Development and Cell Biology 2007- 2015 and as a member of the FEBS Advanced Courses Committee from 2016-2019.

Curriculum Vitae (04/07/2023)

Expertise & keywords

Functional characterization of the sweet taste receptors (Tas1R2/Tas1R3) and TRPM3 in pancreatic beta-cells. Call name: P 1 - SP 1.1 - Proiecte de cercetare Postdoctorală - PD-2021
PN-III-P1-1.1-PD-2021-0076 2022 - 2024

Role in this project:

Coordinating institution: INSTITUTUL DE BIOCHIMIE

Project partners: INSTITUTUL DE BIOCHIMIE (RO)

Affiliation:

Project website: https://sites.google.com/view/tastrip/home

Abstract:

Type-2-diabetes (T2D) affects more than 400 million people worldwide and it is characterized by the inability of the body to manage glucose blood levels due to insulin resistance. G-protein coupled receptors (GPCRs) represent the largest family of membrane receptors, some of which regulate insulin release due to intracellular calcium increase through the downstream activation of voltage-gated calcium ion channels in pancreatic beta-cells. Transient receptor potential (TRP) channels constitute a class of ion channels that show permeability for sodium and calcium ions. Members of the TRP-melastatin (TRPM) family are expressed in pancreatic beta-cells and contribute to insulin release. The main objective of the proposed project is to find novel modulators of the sweet taste-G-protein coupled receptors (Tas1R2/Tas1R3) and to characterize their interaction with the heat-sensitive TRPM3 channels in pancreatic beta-cells. Both proteins contribute to glucose-dependent insulin release but their physiological functions are yet to be determined. For this purpose we will use a high-throughput screening method to identify specific modulators of the Tas1R2/Tas1R3. By monitoring intracellular calcium and glucose-dependent insulin secretion, we will be able to characterize the interactions between the metabotropic receptors and TRPM3. This approach will provide a better understanding of how these proteins relate to insulin secretion and may lead to novel therapeutic strategies.

Defining novel potential therapeutic targets in melanoma immunobiology using a combined proteome-immunopeptidome mass-spectrometry based analysis Call name: P 1 - SP 1.1 - Proiecte de cercetare Postdoctorală
PN-III-P1-1.1-PD-2019-1242 2020 - 2022

Role in this project:

Coordinating institution: INSTITUTUL DE BIOCHIMIE

Project partners: INSTITUTUL DE BIOCHIMIE (RO)

Affiliation: INSTITUTUL DE BIOCHIMIE (RO)

Project website: http://oxprot.tk

Abstract:

The identification of numerous antigens of peptide origin on melanoma cells has placed immunotherapy as one of the most encouraging therapeutic alternative to the classical chemotherapies, which proved a low therapeutic response for metastatic melanoma. This has led the foundation of peptide-based immunotherapy, in which cancer vaccines containing one or several antigens are designed to boost the patient immune system for tumor recognition and rejection by clonal expansion of CD8+ cytotoxic T cells. As a result the search for new antigens with a superior immunological response for cancer treatment is one of the long-standing goals in translational research. One of the most encouraging antigens regarding clinical efficacy is tyrosinase, which undergoes unproductive folding in the endoplasmic reticulum (ER) of melanoma cells. This process leads to the selection of misfolded molecules for degradation and antigenic peptide production in the ubiquitin proteasome pathway. Our previous experiments have revealed that one of the most abundant tyrosinase epitopes presented on the cell surface of melanoma cells YMDGTMSQV (YMD peptide) can be oxidized to both of its Met residues and the oxidized forms results in improved CD8+ T cell activation. Moreover our preliminary results revealed that down regulating the expression level of one out of the four Methionine Sulfoxide Reductases (MSRs) responsible for oxidized Met reduction, results in a similar increased CD8+ T cell recognition suggesting a direct contribution of this enzyme in tumor recognition. Here we would like to address this aspect by analyzing the proteome and HLA-peptidome implications of each of the four intracellular MSRs enzymes (MSRA,MSRB1,MSRB2,MSRB3) using an innovative approach of SILAC (stable isotope labeling by amino acids in cell culture) based chemoproteomic technique. This would open the opportunity to discover novel modified antigens that could show superior immunological responses in immunotherapy.

High-throughput screening platform for small-molecules with anti-inflammatory potential Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2019-3297 2020 - 2022

Role in this project:

Coordinating institution: INSTITUTUL DE BIOCHIMIE

Project partners: INSTITUTUL DE BIOCHIMIE (RO); INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE IN DOMENIUL PATOLOGIEI SI STIINTELOR BIOMEDICALE "VICTOR BABES" (RO)

Affiliation: INSTITUTUL DE BIOCHIMIE (RO)

Project website: https://marichiritoiu4.wixsite.com/ped337

Abstract:

Background: The immune system is the main pillar of the human body’s health. Accurate understanding of the immune modulators will enable us to precisely unveil the abilities of the immune system to fight virtually all human diseases. Chronic inflammation is the hallmark of many human pathologies including cancer and currently, anti-inflammatory therapy is focused on inhibiting production of eicosanoid mediators of inflammation (prostaglandings, thromboxanes, prostacyclins, leukotrienes) by inhibiting their producing enzymes (COX-1/2). Although efficient, recent discoveries emphasized potentially dangerous side effects of these drugs. Therefore, identification and validation of new molecules with anti-inflammatory potential and reduced side effects, becomes of major importance. In the recent years the development of molecules targeting signaling pathways involved in production and release of pro-inflammatory mediators, such as cytokines and chemokines, has gained field and forwards the concept of new-age therapies.

Hypothesis: Our hypothesis is that identifying small molecules, which target the production or secretion of pro-inflammatory cytokines from macrophages and monocytes, such as interleukin-1β (IL-1β), will provide an improved alternative for treating chronic inflammation associated with numerous pathologies.

Aim: This project aims to develop a sensitive high-throughput screening platform by generating an endogenously tagged interleukin-1β reporter cell line by CRISPR-Cas9 technology, able to monitor stimulated IL-1β secretion with the purpose to identify new chemical compounds with anti-inflammatory activity that will be validated in primary macrophages and a mouse model for sepsis.

Expected results: Implementation of this project will deliver a versatile screening platform for anti-inflammatory compounds and a list of validated small molecules with anti-inflammatory properties, which can be easily translated to pre-clinical studies.

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.

Mass spectrometry based investigation of the oxidative stress as a potential key-player in the immunobiology of melanoma Call name: P 1 - SP 1.1 - Proiecte de cercetare Postdoctorală
PN-III-P1-1.1-PD-2016-1528 2018 - 2020

Role in this project:

Coordinating institution: INSTITUTUL DE BIOCHIMIE

Project partners: INSTITUTUL DE BIOCHIMIE (RO)

Affiliation: INSTITUTUL DE BIOCHIMIE (RO)

Project website: http://imunopep.tk

Abstract:

A promising approach of the therapeutic strategy in melanoma is based on cancer cells potential to trigger an immune response by expressing at the cell surface of antigenic peptides derived from proteins such as Melan-A, Gp100, MAGEs, Tyrosinase. This has led to therapies based on cancer vaccines in which an antigenic peptide or a cocktail of antigens are used to boost the immune system of the patient for tumor cell recognition and rejection. This strategy offers the advantages of an increased specificity and a lower toxicity compared with the traditional interventions. One of the most promising melanoma antigens is tyrosinase, which was frequently found as overexpressed in melanomas. It wash shown that this protein undergoes unproductive folding in the endoplasmic reticulum (ER) leading to the selection of the incorrectly folded molecules for degradation via the ubiquitin proteasome system. In this pathway peptides are generated, which can form stable complexes with HLA molecules in ER and be presented to the tumor cell surface for CD8+ T cell recognition and melanoma cell destruction. Our preliminary experiments suggest that the tyrosinase-derived peptide YMDGTMSQV (YMD) presented in complex with HLA-A*0201 can be oxidized to both of the Met residues from its sequence. We have found from immunological CTL assays that a hydrogen peroxide (H2O2) oxidized YMD peptide triggers an increased immune response, in comparison with the native peptide. We aim here to characterize the oxidation forms induced by the H2O2 treatment of the peptide, develop a preparative or semi-preparative method for obtaining these forms, analyze their CD8+ T cell response and study the possibility of intracellular oxidation and presentation of these forms in cells isolated from melanoma patients. This will provide the opportunity to study the tumor immunobiology, whilst obtaining antigens with increased immunogenicity for subsequent use in the immunotherapy of melanoma.

Microfluidic assay of FGF2 therapeutic administration for bone regeneration Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2016-1304 2017 - 2018

Role in this project:

Coordinating institution: INSTITUTUL DE BIOCHIMIE

Project partners: INSTITUTUL DE BIOCHIMIE (RO); INSTITUTUL NATIONAL DE CERCETARE DEZVOLTARE PENTRU FIZICA LASERILOR, PLASMEI SI RADIATIEI - INFLPR RA (RO)

Affiliation: INSTITUTUL DE BIOCHIMIE (RO)

Project website: http://www.biochim.ro/ib/projects/2017-fgf/fgf.php

Abstract:

Musculoskeletal disorders affect 1 in 7 people and fractures alone affect 1 in 50 people annually while 10% of bone injuries fail to heal. Our present proposal aims to test for the first time the potential of fibroblast growth factor-2 (FGF2), to be administered as a stimulatory drug to enhance bone regeneration. Our interdisciplinary approach includes identifying potential positive effect of FGF2 on osteogenic differentiation in an osteo-adipo-inductive environment and screening of specific dosage and temporal administration protocols by using a microfluidic device to control drug perfusion frequency. The innovation of the microfluidic chip will consist of the proposed design and fabrication of channel configuration onto glass surfaces. The developed chip will be connected to a pressure-based flow controller in order to achieve a fluid flow through the micro-channels. The main deliverables of our research and experimental development activities are: i) development of specific lab-on-a-chip devices with capacities of providing chemical stimuli for cellular osteogenic growth and ii) development of specific dosage and temporal administration protocol of FGF2 for efficient enhancement of osteogenic differentiation of mesenchymal stem cells. At the end of the project, our laboratory technological development will generate a proposed schema of administration of the investigated drug using a microfluidic-based approach. This can be used in the future as a platform to screen drugs for bone diseases and to study their mechanism of action.

A robust platform for discovery of novel anti-diabetic therapeutics Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2016-1660 2017 - 2018

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/ib/projects/2017-diab/results_ro.php

Abstract:

We are currently in the middle of a worldwide epidemic of type 2 diabetes mellitus. The hallmark of diabetes is an abnormally elevated concentration of glucose in the blood, due to inadequate production, secretion or responsiveness to insulin, the main hormone that controls glucose levels. We aim to generate stable human cell lines that will be used for accurate, rapid and cheap quantification of secreted insulin. Since blood glucose levels are also regulated by glucagon and glucagon-like peptide 1 (GLP-1), we propose to extend our strategy for quantifying these hormones as well. For decades, insulin secretion has been quantified using Elisa or radioimmunoassay (RIA) kits. These methods have a number of limitations, including specificity, reliability, multiple liquid-handling steps, limited dynamic range, and high cost. We aim to develop a robust luciferase-based assay for insulin, glucagon and GLP-1. We will build fusions between luciferase and pre-pro-hormones, such that, upon hormone processing and secretion, luciferase will be liberated, which, in turn, will allow quantifying hormonal secretion by a simple luciferase assay. Upon comprehensive characterization (including cellular localization of the hormones and quantification of secretion pattern in response to known secretagogues) we have established a system to be used for screening commercial small molecule libraries, to identify novel modulators of secretion of the above-mentioned hormones. Furthermore, we use CRISPR/Cas9 technology to generate secondary cell lines in which genes implicated in insulin maturation and/or secretion are knocked out, thus increasing the repertoire of possible targets in diabetes treatment. In conclusion we will develop a robust platform for the discovery of novel modulators of glucose metabolism.

Fabrication of osteoinductive orthopedic implants with gradual 3D hierarchical structure Call name: Joint Applied Research Projects - PCCA-2011 call, Type 2
PN-II-PT-PCCA-2011-3.2-0898 2012 - 2016

Role in this project:

Coordinating institution: INSTITUTUL NATIONAL DE CERCETARE DEZVOLTARE PENTRU FIZICA LASERILOR, PLASMEI SI RADIATIEI - INFLPR RA

Project partners: INSTITUTUL NATIONAL DE CERCETARE DEZVOLTARE PENTRU FIZICA LASERILOR, PLASMEI SI RADIATIEI - INFLPR RA (RO); INSTITUTUL DE BIOCHIMIE (RO); INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU'' (RO); INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA MATERIALELOR BUCURESTI RA (RO); TEHNOMED IMPEX CO S.A. (RO)

Affiliation: INSTITUTUL DE BIOCHIMIE (RO)

Project website: http://lspi.inflpr.ro/Contracts/Contracts.html

Abstract:

The project “Fabrication of osteoinductive orthopedic implants with gradual 3D hierarchical structure” proposes a novel approach for the ossteointegration of permanent metallic prostheses. The originality of the project consists in the development of implants with 3D hierarchical porous structure characterized by increased surface roughness and wettability, covered with soluble thin multilayer of biocatalytic composites. The resulting structures have the advantage of combining the benefits of deposited biomaterials and the mechanical strength of the metallic collector. The aim of our research is the manufacturing of permanent implants with biofunctional surface which are able to trigger certain healing phases typical for injured bone tissues. The implant fabricated as result of our research will induce complex chronological biological reactions which in the first stage will initiate a vasogenic and angiogenic response succeeded then by the migration and differentiation of osteoblasts and mesenchymal cells and accomplished with the formation of new bone tissue. Thus, the surface structure of the implant with appropriate topology and roughness will serve as framework for osteoconductivity, while further coating with biocomposites acts, in addition to osteoconductivity, as delivery vehicles for cytokines, such as bone morphogenetic proteins, insulin-like growth factors and transforming growth factors, vascular endothelial growth factor, etc. The proposed 3D structures for osteoinduction will mimic bone morphology, structure and function in order to improve the integration into surrounding tissue.

Selection of protein degradative pathways in the pathogenesis of human diseases Call name: Exploratory Research Projects - PCE-2012 call
PN-II-ID-PCE-2012-4-0350 2013 - 2016

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/ib/projects/prodegrad/prodegrad.php

Abstract:

A considerable fraction of all newly synthesized secretory polypeptides fail to attain their native conformation due to mutations, transcriptional and translational errors, folding defects or endoplasmic reticulum (ER) stress conditions. Besides the lack of function, the accumulation of aggregated proteins jeopardize the ER homeostasis and the cell functioning. Terminally misfolded polypeptides are retained and eventually removed by the ER associated degradation pathway(ERAD).We have recently found that besides the mannosidase-like domain, EDEM1 protein, one of the important players of the ERAD has an intrinsically disordered domain with high prediction for favoring protein-protein interactions. Indeed, we showed that this domain is responsible for the interaction with a misfolded tyrosinase mutant. In sum, we suggest that the ER associated degradation of glycoproteins depends less on the glycan recognition signals while rather relying on the direct recognition of the misfolded region of the polypeptide. The aim of this project is to validate this working hypothesis using ERAD substrates involved in tumor antigen degradation/peptide presentation and viral disassembly. Finally, we will use transgenic C.elegans as models for Huntington, Alzheimer and Parkinson diseases, to decipher the pathology and toxicity of protein aggregation. Overall, our approach will reveal new insights into the mechanistic details of the ERAD pathway and help identify new therapeutic targets.

FILE DESCRIPTION	DOCUMENT
List of research grants as project coordinator	Download (13.6 kb) 18/05/2016
List of research grants as partner team leader	Download (13.6 kb) 18/05/2016
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	Download (13.51 kb) 18/05/2016