Livia Sima, Dr.

Livia Sima
Group: Molecular Cell Biology
Department: Molecular Cell Biology

Research Scientist II

Research interests: cancer immune response, tissue transglutaminase, cell signaling, stem cells, bio-nano-technologies

Currently working on

Studying the role of tissue transglutaminase (TG2) in the context of tumor microenvironment and its therapeutic targeting in ovarian cancer
Therapeutic targeting of melanoma cells using nanoparticles as drug delivery vechicles
Modulation of mesenchymal stem cells osteogenic differentiation by extracellular phisico-chemical stimuli (biomaterials, simulated microgravity, growth factors)

Results that stand as premises to my current TG2 research were presented at the STOP CANCER meeting in 2019 (in Romanian): https://youtu.be/r8kcAXT2jEc

An article highlighting our work on graphene was recently published in issue 117 of Research Outreach at page 38: http://cdn.researchoutreach.org/Flipbooks/RO117/index.html; https://researchoutreach.org/articles/targeting-melanoma-cells-drug-infused-graphene-matrix/

Biography

Livia Sima studied biochemistry at the University of Bucharest from where she obtained her bachelor degree in 2003. After graduation she started working at the Institute of Biochemistry where she was accepted to participate in a summer internship programme. Immediately thereafter she joined Stefana Petrescu’s group. She was trained in protein folding using tyrosinase as a model protein. In parallel, she continued her master studies in Biochemistry and Molecular Biology at the University of Bucharest. During her PhD training under Dr. Petrescu’s supervision, Livia worked on two main directions: 1) molecular characterisation of melanoma cell lines expressing the pro-angiogenic chemokine GCP-2 and 2) in vitro osteogenic differentiation of human bone marrow-derived mesenchymal stem cells onto biomaterials designed for prosthetic applications. She was involved in extensive fluorescence microscopy work and successfully implemented flow cytometry methods in IB-AR. Livia received her PhD degree in 2012 from the Romanian Academy. In 2016 she joined Daniela Matei’s group at Northwestern University in Chicago, USA. As a Postdoctoral Fellow, she investigated the role of tissue transglutaminase (TG2) in modulating the anti-tumour immune response in mouse models of ovarian cancer and tested small molecule inhibitors targeting TG2-fibronectin interaction. Livia returned to IB-AR in 2018 with a keen interest in investigating context-dependent cell signaling in the tumour microenvironment and developing new methods related to cancer research. She is currently team leader within TERAMED grant: “Integrated development project for advanced medical treatment technologies” (PN-III-P1-1.2-PCCDI-2017-0728) and principal investigator of the TG2TARGET (PN-III-P1-1.1-TE- 2019-0670) and TG2THERAPY (PN-III-P2-2.1-PED- 2019-1543) research grants. Livia Sima is the Secretary of the Romanian Society for Biochemistry and Molecular Biology (since 2015) and FEBS Member Society Representative (since 2022), Associate Member of the American Association of Cancer Research (AACR) (since 2017) and Member of the Romanian Cytometry Association (ACR) (since 2011). She served as Secretary of the Scientific Committee of the Institute of Biochemistry between 2019 and 2023.

Papers

Year
  • Madalina Icriverzi, Paula Ecaterina Florian, Anca Bonciu, Luminita Nicoleta Dumitrescu, Antoniu Moldovan, Diana Pelinescu, Robertina Ionescu, Ionela Avram, Cristian VA Munteanu, Livia Elena Sima, Valentina Dinca, Laurentiu Rusen, Anca RoseanuMadalina Icriverzi et al . "Hybrid bio-nanoporous peptide loaded-polymer platforms with anticancer and antibacterial activities", Nanoscale Advances, (2024)
    doi: 10.1039/D3NA00947E
    IF: 4.60AI: 0.86
  • Orobeti S, Sima LE, Porosnicu I, Diplasu C, Giubega G, Cojocaru G, Ungureanu R, Dobrea C, Serbanescu M, Mihalcea A, Stancu E, Staicu CE, Jipa F, Bran A, Axente E, Sandel S, Zamfirescu M, Tiseanu I, Sima FOrobeti S et al . "First in vitro cell co-culture experiments using laser-induced high-energy electron FLASH irradiation for the development of anti-cancer therapeutic strategies", Scientific reports 14(1): 14866, (2024)
    doi: 10.1038/s41598-024-65137-7
    IF: 3.80AI: 1.10
  • Balázs Váradi, Károly Brezovcsik, Zoltán Garda, Eniko Madarasi, Horea Szedlacsek, Rodica-Aura Badea, Andrei-Mihai Vasilescu, Adina-Gabriela Puiu, Aura Ionescu, Livia-Elena Sima, Cristian V.A. Munteanu, Simona Călăraș, Adrienn Vagner, Dezső Szikra, Ngô Minh Toàn, Tibor Nagy, Zoltán Szűcs, Stefan Eugen Szedlacsek, Gabor Nagy and Gyula Tircsó.Balázs Váradi et al . "Synthesis and characterization of a novel [52Mn]Mn-labelled affibody based radiotracer for HER2+ targeting", Inorganic Chemistry Frontiers, (2023)
    doi: 10.1039/D3QI00356F
    IF: 7.78AI: 1.01
  • Toderascu LI, Sima LE, Orobeti S, Florian PE, Icriverzi M, Maraloiu V-A, Comanescu C, Iacob N, Kuncser V, Antohe I, Popescu-Pelin G, Stanciu G, Ionita P, Mihailescu CN, Socol GToderascu LI et al . "Synthesis and Anti-Melanoma Activity of L-Cysteine-Coated Iron Oxide Nanoparticles Loaded with Doxorubicin", Nanomaterials 13(4): 621-642, (2023)
    IF: 5.72AI: 0.70
  • Rus AA, Militaru IV, Popa I, Munteanu CVA, Sima LE, Platt N, Platt FM, Petrescu ȘMRus AA et al . "NPC1 plays a role in the trafficking of specific cargo to melanosomes", Journal of Biological Chemistry(Aug;299(8):105024), (2023)
    doi: doi: 10.1016/j.jbc.2023.105024
    IF: 5.50AI: 1.40
  • Sima LE, Matei D, Condello SSima LE et al . "The Outside-In Journey of Tissue Transglutaminase in Cancer", Cells 11(11), (2022)
    IF: 6.60
  • Sima LE, Chen S, Cardenas H, Zhao G, Wang Y, Ivan C, Huang H, Zhang B, Matei DSima LE et al . "Loss of host tissue transglutaminase boosts antitumor T cell immunity by altering STAT1/STAT3 phosphorylation in ovarian cancer", Journal for ImmunoTherapy of Cancer(9): e002682, (2021)
    IF: 13.75
  • Bonciu AF, Orobeti S, Sima LE, Icriverzi M, Filipescu M, Moldovan A, Popescu A, Dinca V, Dinescu M, Bonciu AF et al . "Pyramidal shaped ceria nano-biointerfaces for studying the early bone cell response", Applied Surface Science 533(10): 147464, (2020)
    IF: 6.70AI: 0.60
  • Boteanu RM, Suica VI, Ivan L, Safciuc F, Uyy E, Dragan E, Croitoru SM, Grumezescu V, Chiritoiu M, Sima LE, Vlagioiu C, Socol G, Antohe FBoteanu RM et al . "Proteomics of regenerated tissue in response to a titanium implant with a bioactive surface in a rat tibial defect model", Scientific reports 10(1): 18493, (2020)
    IF: 3.99AI: 1.90
  • Sima LE, Chiritoiu G, Negut I, Grumezescu V, Orobeti S, Munteanu CVA, Sima F, Axente ESima LE et al . "Functionalized Graphene Oxide Thin Films for Anti-tumor Drug Delivery to Melanoma Cells", Frontiers in chemistry 8: 184, (2020)
    IF: 3.70
  • Visan AI, Popescu-Pelin G, Gherasim O, Mihailescu A, Socol M, Zgura I, Chiritoiu M, Elena Sima L, Antohe F, Ivan L, Vranceanu DM, M Cotruț C, Cristescu R, Socol GVisan AI et al . "Long-Term Evaluation of Dip-Coated PCL-Blend-PEG Coatings in Simulated Conditions", Polymers 12(3), (2020)
    IF: 3.42AI: 0.90
  • Sima LE, Yakubov B, Zhang S, Condello S, Grigorescu AA, Nwani N, Chen L, Schiltz G, Arvanitis C, Zhang ZY, Matei DSima LE et al . "Small Molecules Target the Interaction between Tissue Transglutaminase and Fibronectin", Molecular Cancer Therapeutics 6(18): 1057-1068, (2019)
    IF: 4.86AI: 1.90
  • Brixhilda Domi, Carlos Rumbo, Javier García-Tojal, Livia Elena Sima, Gabriela Negroiu, Juan Antonio Tamayo-RamosBrixhilda Domi et al . "Interaction Analysis of Commercial Graphene Oxide Nanoparticles with Unicellular Systems and Biomolecules", International Journal of Molecular Science 205(21): 1-19, (2019)
    doi: 10.3390/ijms21010205
    IF: 4.50
  • Ionescu AE, Mentel M, Munteanu CVA, Sima LE, Martin EC, Necula-Petrareanu G, Szedlacsek SEIonescu AE et al . "Analysis of EYA3 Phosphorylation by Src Kinase Identifies Residues Involved in Cell Proliferation", International Journal of Molecular Sciences 20(24): 6307, (2019)
    IF: 4.18
  • Icriverzi M, Bonciu A, Rusen L, Sima LE, Brajnicov S, Cimpean A, Evans RW, Dinca V, Roseanu AIcriverzi M et al . "Human Mesenchymal Stem Cell Response to Lactoferrin-based Composite Coatings", Materials (Basel, Switzerland) 12(20), (2019)
    IF: 2.97AI: 0.80
  • Icriverzi M, Rusen L, Brajnicov S, Bonciu A, Dinescu M, Cimpean A, Evans RW, Dinca V, Roseanu AIcriverzi M et al . "Macrophage in vitro Response on Hybrid Coatings Obtained by Matrix Assisted Pulsed Laser Evaporation", Coatings(9), (2019)
    IF: 2.35
  • Condello S, Sima L, Ivan C, Cardenas H, Schiltz G, Mishra RK, Matei DCondello S et al . "Tissue Tranglutaminase Regulates Interactions between Ovarian Cancer Stem Cells and the Tumor Niche", Cancer research 78(11): 2990-3001, (2018)
    doi: https://doi.org/10.1158/0008-5472.CAN-17-2319
    IF: 8.38AI: 3.20
  • M. Icriverzi, L. Rusen, L. E. Sima, A. Moldovan, S. Brajnicov, A. Bonciu, N. Mihailescu, M. Dinescu, A. Cimpean, A. Roseanu, V. DincaM. Icriverzi et al . "In vitro behavior of human mesenchymal stem cells on poly(N-isopropylacrylamide) based biointerfaces obtained by matrix assisted pulsed laser evaporation", Applied Surface Science 440: 712-724, (2018)
    IF: 5.16AI: 0.60
  • Popescu A C, Florian P E, Stan G E, Popescu-Pelin G, Zgura I, Enculescu M, Oktar F N, Trusca R, Sima L E, Roseanu A, Duta LPopescu A C et al . "Physical-chemical characterization and biological assessment of simple and lithium-doped biological-derived hydroxyapatite thin films for a new generation of metallic implants", Applied Surface Science 439: 724-735, (2018)
    IF: 5.15AI: 0.60
  • Popescu A., Florian P., Stan G., Popescu-Pelin G., Zgura I., Enculescu M., Oktar F., Trusca R., Sima L., Roseanu APopescu A. et al . "Physical-chemical characterization and biological assessment of simple and lithium-doped biological-derived hydroxyapatite thin films for a new generation of metallic implants", (Applied Surface Science), (2018)
  • Nwani NG, Sima LE, Nieves-Neira W, Matei DNwani NG et al . "Targeting the Microenvironment in High Grade Serous Ovarian Cancer", Cancers 10(8), (2018)
  • Scarisoreanu ND, Craciun F, Ion V, Birjega R, Bercea A, Dinca V, Dinescu M, Sima LE, Icriverzi M, Roseanu A, Gruionu L, Gruionu GScarisoreanu ND et al . "Lead-Free Piezoelectric (Ba,Ca)(Zr,Ti)O3 Thin Films for Biocompatible and Flexible Devices", ACS applied materials & interfaces 9(1): 266-278, (2017)
    IF: 8.30AI: 1.50
  • Uta M, Sima LE, Hoffmann P, Dinca V, Branza-Nichita NUta M et al . "Development of a DsRed-expressing HepaRG cell line for real-time monitoring of hepatocyte-like cell differentiation by fluorescence imaging, with application in screening of novel geometric microstructured cell growth substrates", Biomedical microdevices 19(1): 3, (2017)
    IF: 2.08AI: 0.70
  • A Visan, R Cristescu, N Stefan, M Miroiu, C Nita, M Socol, C Florica, O Rasoga, I Zgura, LE Sima, M Chiritoiu, MC Chifiriuc, AM Holban, IN Mihailescu, G SocolA Visan et al . "Antimicrobial polycaprolactone/polyethylene glycol embedded lysozyme coatings of Ti implants for osteoblast functional properties in tissue engineering", Applied Surface Science 417: 234-243, (2017)
    AI: 0.60
  • Rașoga O, Sima L, Chirițoiu M, Popescu-Pelin G, Fufă O, Grumezescu V, Socola M, Stănculescu A, Zgură I, Socol GRașoga O et al . "Biocomposite coatings based on Poly (3-hydroxybutyrate-co-3-hydroxyvalerate)/calcium phosphates obtained by MAPLE for bone tissue engineering", Applied Surface Science 417: 204-212, (2017)
    AI: 0.60
  • Rusen, L.; Dinca, V.; Mustaciosu, C.; Icriverzi, M.; Sima, L.E.; Bonciu, A.; Brajnicov, S.; Mihailescu, N.; Dumitrescu, N.; Popovici, A.I., Roseanu A.; Dinescu MRusen et al . "Modern Technologies for Creating the Thin-Film Systems and Coatings", : 171-191, (2017)
  • Grumezescu V, Holban AM, Sima LE, Chiritoiu MB, Chiritoiu GN, Grumezescu AM, Ivan L, Safciuc F, Antohe F, Florica C, Luculescu CR, Chifiriuc MC, Socol GGrumezescu V et al . "Laser deposition of poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid) - lysozyme microspheres based coatings with anti-microbial properties", International journal of pharmaceutics 521(1-2): 184-195, (2017)
    AI: 0.80
  • Sima LE. "Extracellular Signals for Guiding Mesenchymal Stem Cells Osteogenic Fate", Current stem cell research & therapy 12(2): 139-144, (2017)
  • Popa IL, Milac AL, Sima LE, Alexandru PR, Pastrama F, Munteanu CV, Negroiu GPopa IL et al . "Cross-talk between Dopachrome Tautomerase and Caveolin-1 Is Melanoma Cell Phenotype-specific and Potentially Involved in Tumor Progression", The Journal of biological chemistry 291(24): 12481-500, (2016)
    IF: 4.12
  • Ulmeanu M, Sima LE, Ursescu D, Enculescu M, Bazan X, Quintana IUlmeanu M et al . "Cell adhesion response on femtosecond laser initiated liquid assisted silicon surface", Current topics in medicinal chemistry 14(5): 624-9, (2014)
    IF: 3.40AI: 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)
  • Dinca V, Florian PE, Sima LE, Rusen L, Constantinescu C, Evans RW, Dinescu M, Roseanu ADinca V et al . "MAPLE-based method to obtain biodegradable hybrid polymeric thin films with embedded antitumoral agents", Biomedical microdevices 16(1): 11-21, (2014)
  • Corotchi MC, Popa MA, Remes A, Sima LE, Gussi I, Lupu Plesu MCorotchi MC et al . "Isolation method and xeno-free culture conditions influence multipotent differentiation capacity of human Wharton's jelly-derived mesenchymal stem cells", Stem cell research & therapy 4(4): 81, (2013)
    IF: 4.63AI: 1.30
  • Sima LE, Buruiana EC, Buruiana T, Matei A, Epurescu G, Zamfirescu M, Moldovan A, Petrescu SM, Dinescu MSima LE et al . "Dermal cells distribution on laser-structured ormosils", Journal of tissue engineering and regenerative medicine 7(2): 129-38, (2013)
    AI: 1.00
  • Filimon A, Sima LE, Appelhans D, Voit B, Negroiu GFilimon A et al . "Internalization and intracellular trafficking of poly(propylene imine) glycodendrimers with maltose shell in melanoma cells", Current medicinal chemistry 19(29): 4955-68, (2012)
    IF: 4.07AI: 1.20
  • Ivan V, Martinez-Sanchez E, Sima LE, Oorschot V, Klumperman J, Petrescu SM, van der Sluijs PIvan V et al . "AP-3 and Rabip4' coordinately regulate spatial distribution of lysosomes", PloS one 7(10): e48142, (2012)
    IF: 3.73AI: 1.50
  • Florian P, Macovei A, Sima L, Nichita N, Mattsby-Baltzer I, Roseanu AFlorian P et al . "Endocytosis and trafficking of human lactoferrin in macrophage-like human THP-1 cells (1)", Biochemistry and cell biology = Biochimie et biologie cellulaire 90(3): 449-55, (2012)
    IF: 2.92
  • Sima F, Davidson P, Pauthe E, Sima LE, Gallet O, Mihailescu IN, Anselme KSima F et al . "Fibronectin layers by matrix-assisted pulsed laser evaporation from saline buffer-based cryogenic targets", Acta biomaterialia 7(10): 3780-8, (2011)
    IF: 4.87AI: 1.30
  • Sima F, Mutlu EC, Eroglu MS, Sima LE, Serban N, Ristoscu C, Petrescu SM, Oner ET, Mihailescu INSima F et al . "Levan nanostructured thin films by MAPLE assembling", Biomacromolecules 12(6): 2251-6, (2011)
  • Sima F, Ristoscu C, Caiteanu D, Mihailescu CN, Stefan N, Mihailescu IN, Prodan G, Ciupina V, Palcevskis E, Krastins J, Sima LE, Petrescu SMSima F et al . "Biocompatibility and bioactivity enhancement of Ce stabilized ZrO(2) doped HA coatings by controlled porosity change of Al(2) O(3) substrates", Journal of biomedical materials research. Part B, Applied biomaterials 96(2): 218-24, (2011)
  • Sima F, Axente E, Ristoscu C, Mihailescu IN, Kononenko TV, Nagovitsin IA, Chudinova G, Konov VI, Socol M, Enculescu I, Sima LE, Petrescu SMSima F et al . "Tailoring immobilization of immunoglobulin by excimer laser for biosensor applications", Journal of biomedical materials research. Part A 96(2): 384-94, (2011)
  • Sima LE, Stan GE, Morosanu CO, Melinescu A, Ianculescu A, Melinte R, Neamtu J, Petrescu SMSima LE et al . "Differentiation of mesenchymal stem cells onto highly adherent radio frequency-sputtered carbonated hydroxylapatite thin films", Journal of biomedical materials research. Part A 95(4): 1203-14, (2010)
    IF: 3.04
  • Roseanu A, Florian PE, Moisei M, Sima LE, Evans RW, Trif MRoseanu A et al . "Liposomalization of lactoferrin enhanced its anti-tumoral effects on melanoma cells", Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 23(3): 485-92, (2010)
  • Sima LE, Filimon A, Piticescu RM, Chitanu GC, Suflet DM, Miroiu M, Socol G, Mihailescu IN, Neamtu J, Negroiu GSima LE et al . "Specific biofunctional performances of the hydroxyapatite-sodium maleate copolymer hybrid coating nanostructures evaluated by in vitro studies", Journal of materials science. Materials in medicine 20(11): 2305-16, (2009)
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Grants

Role of TG2 in cancer tumor microenvironment for guiding metastasis prevention therapeutic approaches 2020-2022
Acronym: TG2TARGET
Budget: 431,900 RON
Project director: Livia Sima

The overall goal of the current project is to understand the impact of tissue transglutaminase (TG2) targeting in the context of ovarian cancer (OC) tumor microenvironment (TME). Our aproach is aimed at testing the hypothesis that interventions in targeting TG2 in the OC TME will disrupt pro-tumorigenic signaling cross-talk within tumors.

Context-dependent therapeutic targeting of ovarian cancer metastasis using TG2 small molecule inhibitors 2020-2022
Acronym: TG2THERAPY
Budget: 600,000 RON
Project director: Livia Sima

The principal goal of this project is the development of a new class of small molecule inhibitors (SMIs) targeting TG2-FN interaction, which is currently in the phase of lead optimization, translatable to clinical use for prevention of ovarian cancer dissemination, either alone or in combinations.