Stefana-Maria Petrescu, Dr.

Stefana-Maria Petrescu
Group: Molecular Cell Biology
Department: Molecular Cell Biology

Director of Institute, Head of Department

Research interests: Dr Petrescu's research aims to understand the folding and degradation pathways regulating protein synthesis and maturation within the endoplasmic reticulum of mammalian cells. Tyrosinase related proteins were chosen as model systems for glycoprotein folding due to the extreme complexity of the process along the maturation pathway. Since tyrosinase regulates melanogenesis in melanocytes and melanoma cells, the cell biology of these two cell types is a major focus of her research. Other major research topics include: -Protein degradation associated with the ER, ERAD, and the particular function of EDEM family proteins in this pathway - Proinsulin folding and maturation within the ER, a process that influences proinsulin conversion to insulin and insulin secretion in the pancreatic islets - Role of ERAD in the antigen processing and presentation pathway and discovery of new antigenic peptides in melanoma

Biography

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 investigated the glycobiology of tyrosinase from melanoma cells contributing to the fundamental mechanisms of calnexin associated folding and quality control of glycoproteins. She proposed tyrosinase as a model glycoprotein for the investigation of the endoplasmic reticulum quality control and protein degradation in ERAD. Dr. Petrescu has been granted the Award Emil Racovita of the Romanian Academy for the work on tyrosinase folding in 2002. She is President of the Romanian Society of Biochemistry and Molecular Biology since 2010. 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. She is Deputy- Editor of Molecular Life.

Papers

Year
  • Chiritoiu G., Munteanu CVA., Sulea TA., Spiridon L., Petrescu AJ., Jandus C., Romero P., Petrescu SM.Chiritoiu G. et al . "Methionine oxidation selectively enhances T cell reactivity against a melanoma antigen", iScience(107205), (2023)
    doi: 10.1016/j.isci.2023.107205
    IF: 6.10AI: 1.63
  • Flintoaca Alexandru PR, Chiritoiu GN, Lixandru D, Zurac S, Ionescu-Targoviste C, Petrescu SMFlintoaca Alexandru PR et al . "EDEM1 regulates the insulin mRNA level by inhibiting the endoplasmic reticulum stress-induced IRE1/JNK/c-Jun pathway", iScience 26(10): 107956, (2023)
    doi: 10.1016/j.isci.2023.107956
    IF: 6.10AI: 1.63
  • Militaru IV, Rus AA, Munteanu CVA, Manica G, Petrescu SMMilitaru IV et al . "New panel of biomarkers to discriminate between amelanotic and melanotic metastatic melanoma", Frontiers in oncology 12: 1061832, (2023)
    doi: doi: 10.3389/fonc.2022.1061832
    IF: 5.74AI: 1.15
  • Munteanu CVA, Chirițoiu GN, Petrescu AJ, Petrescu ȘMMunteanu CVA et al . "Defining the altered glycoproteomic space of the early secretory pathway by class I mannosidase pharmacological inhibition", Frontiers in molecular biosciences 9: 1064868, (2022)
    IF: 6.11AI: 1.33
  • Ghenea S, Chiritoiu M, Tacutu R, Miranda-Vizuete A, Petrescu SMGhenea S et al . "Targeting EDEM protects against ER stress and improves development and survival in C. elegans", PLoS genetics 18(2): e1010069, (2022)
    IF: 5.90AI: 2.47
  • Munteanu CVA, Chirițoiu GN, Chirițoiu M, Ghenea S, Petrescu AJ, Petrescu ȘMMunteanu CVA et al . "Affinity proteomics and deglycoproteomics uncover novel EDEM2 endogenous substrates and an integrative ERAD network", Molecular & cellular proteomics : MCP: 100125, (2021)
    IF: 5.91AI: 2.26
  • Manica G, Ghenea S, Munteanu CVA, Martin EC, Butnaru C, Surleac M, Chiritoiu GN, Alexandru PR, Petrescu AJ, Petrescu SMManica G et al . "EDEM3 Domains Cooperate to Perform Its Overall Cell Functioning", Int. J. Mol. Sci. 4(22): 2172, (2021)
    IF: 4.56AI: 0.80
  • Chiritoiu M, Chiritoiu GN, Munteanu CVA, Pastrama F, Ivessa NE and Petrescu SMChiritoiu M et al . "EDEM1 Drives Misfolded Protein Degradation via ERAD and Exploits ER-Phagy as Back-Up Mechanism When ERAD Is Impaired", International Journal of Molecular Sciences 10(21): 3468, (2020)
    IF: 4.10
  • Munteanu CVA, Chiritoiu GN, Petrescu AJ, Petrescu ȘMMunteanu CVA et al . "Profiling Optimal Conditions for Capturing EDEM Proteins Complexes in Melanoma Using Mass Spectrometry", Advances in experimental medicine and biology 1140: 155-167, (2019)
    IF: 2.13
  • Butnaru CM, Chiritoiu MB, Chiritoiu GN, Petrescu SM, Petrescu AJButnaru CM et al . "Inhibition of N-glycan processing modulates the network of EDEM3 interactors", Biochemical and biophysical research communications 486(4): 978-984, (2017)
    IF: 2.56
  • Lazar C, Uta M, Petrescu SM, Branza-Nichita NLazar C et al . "Novel function of the endoplasmic reticulum degradation-enhancing α-mannosidase-like proteins in the human hepatitis B virus life cycle, mediated by the middle envelope protein", Cellular microbiology 19(2), (2017)
  • Chiritoiu GN, Jandus C, Munteanu CV, Ghenea S, Gannon PO, Romero P, Petrescu SMChiritoiu GN et al . "Epitope located N-glycans impair the MHC-I epitope generation and presentation", Electrophoresis 37(11): 1448-60, (2016)
    IF: 2.74
  • Cucu D, Chiritoiu G, Petrescu S, Babes A, Stanica L, Duda DG, Horii A, Dima SO, Popescu ICucu D et al . "Characterization of functional transient receptor potential melastatin 8 channels in human pancreatic ductal adenocarcinoma cells", Pancreas 43(5): 795-800, (2014)
    IF: 2.96AI: 0.90
  • Filimon A, Zurac SA, Milac AL, Sima LE, Petrescu SM, Negroiu GFilimon A et al . "Value of dopachrome tautomerase detection in the assessment of melanocytic tumors", Melanoma research 24(3): 219-36, (2014)
  • Lazar C, Macovei A, Petrescu S, Branza-Nichita NLazar C et al . "Activation of ERAD pathway by human hepatitis B virus modulates viral and subviral particle production", PloS one 7(3): e34169, (2012)
    IF: 3.73AI: 1.50
  • Marin MB, Ghenea S, Spiridon LN, Chiritoiu GN, Petrescu AJ, Petrescu SMMarin MB et al . "Tyrosinase degradation is prevented when EDEM1 lacks the intrinsically disordered region", PloS one 7(8): e42998, (2012)
  • Cioaca D, Ghenea S, Spiridon LN, Marin M, Petrescu AJ, Petrescu SMCioaca D et al . "C-terminus glycans with critical functional role in the maturation of secretory glycoproteins", PloS one 6(5): e19979, (2011)
    IF: 4.09AI: 1.80
  • Negroiu G, Dwek RA, Petrescu SMNegroiu G et al . "Tyrosinase-related protein-2 and -1 are trafficked on distinct routes in B16 melanoma cells", Biochemical and biophysical research communications 328(4): 914-21, (2005)
  • Negroiu G, Dwek RA, Petrescu SMNegroiu G et al . "The inhibition of early N-glycan processing targets TRP-2 to degradation in B16 melanoma cells", The Journal of biological chemistry 278(29): 27035-42, (2003)
  • Branza-Nichita N, Petrescu AJ, Negroiu G, Dwek RA, Petrescu SMBranza-Nichita N et al . "N-glycosylation processing and glycoprotein folding-lessons from the tyrosinase-related proteins", Chemical reviews 100(12): 4697-712, (2000)
  • Negroiu G, Dwek RA, Petrescu SMNegroiu G et al . "Folding and maturation of tyrosinase-related protein-1 are regulated by the post-translational formation of disulfide bonds and by N-glycan processing", The Journal of biological chemistry 275(41): 32200-7, (2000)
  • Petrescu SM, Branza-Nichita N, Negroiu G, Petrescu AJ, Dwek RAPetrescu SM et al . "Tyrosinase and glycoprotein folding: roles of chaperones that recognize glycans", Biochemistry 39(18): 5229-37, (2000)
  • Branza-Nichita N, Negroiu G, Petrescu AJ, Garman EF, Platt FM, Wormald MR, Dwek RA, Petrescu SMBranza-Nichita N et al . "Mutations at critical N-glycosylation sites reduce tyrosinase activity by altering folding and quality control", The Journal of biological chemistry 275(11): 8169-75, (2000)
  • Negroiu G, Branza-Nichita N, Costin GE, Titu H, Petrescu AJ, Dwek RA, Petrescu SMNegroiu G et al . "Investigation of the intracellular transport of tyrosinase and tyrosinase related protein (TRP)-1. The effect of endoplasmic reticulum (ER)-glucosidases inhibition", Cellular and molecular biology (Noisy-le-Grand, France) 45(7): 1001-10, (1999)
  • Negroiu G, Branza-Nichita N, Petrescu AJ, Dwek RA, Petrescu SMNegroiu G et al . "Protein specific N-glycosylation of tyrosinase and tyrosinase-related protein-1 in B16 mouse melanoma cells", The Biochemical journal 344 Pt 3: 659-65, (1999)
  • Petrescu AJ, Butters TD, Reinkensmeier G, Petrescu S, Platt FM, Dwek RA, Wormald MRPetrescu AJ et al . "The solution NMR structure of glucosylated N-glycans involved in the early stages of glycoprotein biosynthesis and folding", The EMBO journal 16(14): 4302-10, (1997)
  • Zapun A, Petrescu SM, Rudd PM, Dwek RA, Thomas DY, Bergeron JJZapun A et al . "Conformation-independent binding of monoglucosylated ribonuclease B to calnexin", Cell 88(1): 29-38, (1997)
    AI: 26.40
  • Surleac MD, Spiridon LN, TacutuR, Milac AL, Petrescu SM, Petrescu AJSurleac MD et al . "Structural Assessment of Glycosylation Sites Database - SAGS – An Overall View on N-Glycosylation", pp 3-20, Glycosilation, InTech, (2012).
    ISBN: 978-953-51-0771-2
View all papers

Grants

Dezvoltarea infrastructurii de cercetare a Institutului de Biochimie in vederea cresterii competitivitatii in domeniul proteomicii biomedicale 2010-2012
Acronym: PROCERA
Project director: Stefana-Maria Petrescu

Scopul PROCERA este de a dezvolta infrastructura IBAR pentru cresterea capacitatii de cercetare-dezvoltare C-D in domeniul biochimiei si biologiei moleculare pe plan national, precum si a competitivitatii cercetarii stiintifice romanesti la nivel european.

Biotehnologii Celulare si Moleculare cu Aplicatii in Medicina 2010-2013
Acronym: Programul Postdoctoral
Project director: Stefana-Maria Petrescu

Programul Postdoctoral "Biotehnologii Celulare si Moleculare cu Aplicatii in Medicina", se adreseaza tinerilor cu diploma de doctor in biologie, chimie, fizica, medicina si informatica - interesati de burse de cercetare Post Doctorala la standarde europene.

In vitro evaluation of potential biomedical strategies aimed to prevent bone loss during spaceflight 2017-2019
Acronym: SPACEBONE
Project director: Stefana-Maria Petrescu

Bone loss represents one of the most important health problems experienced by Space travelling astronauts. Microgravity produces deterioration of the skeleton due to lack of mechanical loading thus affecting both muscle and bones. Tendons stiffness decreases, muscle fibres atrophies and attenuates their metabolic capacity, whileprogressive cartilage loss occurs.

Role of the ERAD pathway in the degradation of tyrosinase and production of antigenic peptides in human melanoma 2012-2015
Acronym: TYRPRES
Project director: Stefana-Maria Petrescu

A detailed knowledge of the mechanisms of antigen processing and presentation is essential to optimize cancer vaccination. known as Endoplasmic Reticulum Associated Degradation (ERAD). Non cytosolic misfolded proteins, synthesized at the endoplasmic reticulum are degraded to peptides by a complex machinery Cancer immunotherapy aims at harnessing the resources of the immune system to treat cancer.

Selectia cailor de degradare a proteinelor in patogeneza bolilor umane 2013-2015
Acronym: PRODEGRAD
Project director: Stefana-Maria Petrescu

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.

Mass spectrometry based investigation of the oxidative stress as a potential key-player in the immunobiology of melanoma 02/05/2018 - 31/08/2020
Acronym: IMUNOPEP
Budget: 250 000 RON
Project director: Cristian Munteanu

High-throughput screening platform for small-molecules with anti-inflammatory potential 2020-2022
Acronym: HTS-IL-1β
Budget: 600.000 RON
Project director: Marioara Chiritoiu-Butnaru

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.

IDENTIFICATION OF IL-1Β CYTOKINE SECRETION MODULATORS TARGETED BY REPOSITIONED DRUGS 2023-2025
Acronym: RepozIL
Budget: 200.000 RON
Project director: Marioara Chiritoiu-Butnaru