BrainMap

LIVIA ELENA SIMA

Dr.

Scientific Researcher II - INSTITUTUL DE BIOCHIMIE

Researcher | Scientific reviewer

Between 1999-2003 I studied biochemistry at the University of Bucharest. After graduation I was accepted as a research assistant at the Institute of Biochemistry (IB-AR) and continued my master studies in Biochemistry and Molecular Biology. During that time, I was trained in protein folding using tyrosinase as a model protein. As PhD student under Dr. Petrescu’s supervision, I worked on melanoma biology and stem cell differentiation on biomaterials. I have successfully implemented flow cytometry and quantitative imaging methods in IB-AR. I have received the PhD degree in 2012 from the Romanian Academy. In 2016 I joined Daniela Matei’s group at Northwestern University in Chicago, USA. As a Postdoctoral Fellow, my topics were the investigation of the role of tissue transglutaminase (TG2) in modulating the anti-tumour immune response in mouse models of ovarian cancer and its therapeutic targeting. In 2018 I returned to IB-AR to research context-dependent cell signaling in ovarian tumors.

Web of Science ResearcherID: C-2882-2011

Curriculum Vitae (09/02/2024)

Expertise & keywords

Mobilitate cercetător cu experiență din diaspora Daniela Matei Call name: PNCDI IV, P 5.2 - SP 5.2.2 - Proiecte de mobilitate pentru cercetători cu experiență din diaspora, MCD-2023
PN-IV-P2-2.2-MCD-2023-0081 2023 - 2023

Role in this project:

Coordinating institution: INSTITUTUL DE BIOCHIMIE

Project partners: INSTITUTUL DE BIOCHIMIE (RO)

Affiliation:

Project website:

Abstract:

Role of TG2 in cancer tumor microenvironment for guiding metastasis prevention therapeutic approaches Call name: P 1 - SP 1.1 - Proiecte de cercetare pentru stimularea tinerelor echipe independente
PN-III-P1-1.1-TE-2019-0670 2020 - 2022

Role in this project: Project coordinator

Coordinating institution: INSTITUTUL DE BIOCHIMIE

Project partners: INSTITUTUL DE BIOCHIMIE (RO)

Affiliation: INSTITUTUL DE BIOCHIMIE (RO)

Project website: http://www.biochim.ro/grant-29-tg2target/

Abstract:

Ovarian cancer (OC) is the leading cause of death among gynecological malignancies. Due to the insidious symptoms, it is diagnosed in late stages (III/IV) when the cancer cells have already disseminated. A major issue in the management of this disease is that OC tumors develops resistance to drugs used in front line treatment (platinum- and taxol-based compounds). Over the past decade, several studies have reported tissue transglutaminase (TG2) overexpression in cancer. Specifically, in OC, TG2 has been shown to promote all stages of tumor progression and has been linked to chemotherapeutic resistance. Our recent data suggest decreased tumor burden concurrently with increased infiltration, activation and effector functions of T cells, and loss of immunosuppressive signals in the tumor microenvironment (TME) resulting in development of an anti-tumorigenic phenotype in TG2 knock-out mice. Based on this evidence, TG2 therapeutic targeting shows a lot of promise for the management of metastatic ovarian cancer. In OC, it is already known that stromal and immune factors in the tumor microenvironment are modulating cancer cells/spheroids adhesion and invasion capacity We propose here fundamental research activities aimed to generate a better understanding of the role of TG2 in the context of TME using inhibitors as tools for deciphering cell communication pathways between different lineages in the tumor and also, to test combinations of TG2 inhibitors and drugs targeting the metastatic niche signaling to evaluate their potential in blocking OC dissemination.

Enhanced magnetic hyperthermia for malignant melanoma therapy Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2019-3292 2020 - 2022

Role in this project: Partner team leader

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 NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA MATERIALELOR BUCURESTI RA (RO)

Affiliation: INSTITUTUL DE BIOCHIMIE (RO)

Project website: http://ema-hypermat.inflpr.ro

Abstract:

The main objective of the project “Enhanced magnetic hyperthermia for malignant melanoma therapy” (EMA-HYPERMAT) is to increase the level of TRL maturity of a technology for treatment of the malignant melanoma by means of magnetic hyperthermia, implying drug delivery nanosystems developed by us. Nanoparticles could be efficient cytostatic delivery systems, capable of tumor targeting; thereby, the use of such nanosystems decrease adverse effects, increase therapy effectiveness, and increase the survival of skin cancer patients. The combination of chemotherapeutics and hyperthermia can be adjusted, depending on the type and site of the tumor, also on the drug dose and temperature. We propose to combine the advantages of hyperthermia with the controlled delivery of the antitumoral loaded into magnetic particle systems. In this respect, the novelty of our proposal is related on the use of hyperthermia enhancers based on the combination of iron oxide/silica core-shell particles and superparamagnetic iron oxide nanoparticles (SPIONs) embedded into the thermoplastic polymeric nanospheres. Both particle systems bring specific advantages. For such formulations, smaller concentrations of the iron oxide nanoparticles are necessary in order to obtain similar performances in hyperthermia tests which results in lower toxicity, reduced immunogenicity and side effects while magnetic polymeric nanospheres will provide improved efficiency in the case of hyperthermia and a better drug release due to the higher loading capacity of the polymer matrix.

Context-dependent therapeutic targeting of ovarian cancer metastasis using TG2 small molecule inhibitors Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2019-1543 2020 - 2022

Role in this project: Project coordinator

Coordinating institution: INSTITUTUL DE BIOCHIMIE

Project partners: INSTITUTUL DE BIOCHIMIE (RO)

Affiliation: INSTITUTUL DE BIOCHIMIE (RO)

Project website: http://www.biochim.ro/grant-30-tg2therapy/

Abstract:

Ovarian cancer (OC) is the leading cause of death among gynecological malignancies. Due to the insidious symptoms, it is diagnosed in late stages when the cancer cells have already disseminated. A major issue in the management of this disease is that OC tumors develops resistance to drugs used in front line treatment. Over the past decade, several studies have reported tissue transglutaminase (TG2) overexpression in cancer. Specifically, in OC, TG2 has been shown to promote all stages of tumor progression. TG2 was found to be highly expressed in ovarian cancer stem cells and linked to chemotherapy resistance. Our recent data suggest decreased tumor burden concurrently with increased infiltration, activation and effector functions of T cells, and loss of immunosuppressive signals in the tumor microenvironment resulting in development of an anti-tumorigenic phenotype in TG2 knock-out mice. The physiological roles of TG2 are regulated by cellular context and localization. At the plasma membrane, TG2 binds to the gelatin-binding domain of fibronectin (FN) with high affinity and this complex provides a binding site for beta 1 and beta 3 integrins thus increasing cells capacity to attach and migrate onto the metastatic niche. In this project we aim at developing new inhibitors targeting the TG2-FN interaction. We propose new drug development activities for testing second generation compounds with improved pharmacokinetics features and to assess TG2 inhibitors’ potential to be used as anti-metastatic drugs in combination with other chemo- and immune-therapeutic agents.

Integrated development project for advanced medical treatment technologies Call name: P 1 - SP 1.2 - Proiecte complexe realizate in consorții CDI
PN-III-P1-1.2-PCCDI-2017-0728 2018 - 2021

Role in this project: Partner team leader

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 NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO” (RO); INSTITUTUL DE BIOCHIMIE (RO); UNIVERSITATEA BUCURESTI (RO); UNIVERSITATEA PITESTI (RO)

Affiliation: INSTITUTUL DE BIOCHIMIE (RO)

Project website: http://teramed.inflpr.ro/

Abstract:

In order to increase community’s quality of life, the aim of the project proposal entitled “Integrated development project for advanced medical treatment technologies” (TERAMED) is to develop novel technologies with respect to the treatment of osseous and cutaneous conditions and oncological disorders. Given our experience in healthcare research and the current requirements of multidisciplinary and interinstitutional collaboration towards the personalized treatment purpose, the TERAMED project aims genuine synthesis and processing of biomaterials, but also functional and therapeutic evaluation relevant for clinical trials. The main objectives of the “Medical devices functionalized by laser technologies and alternatives for enhanced osseous integration and regeneration” subproject are to design and produce inorganic, composite or hybrid coatings for superior osteoconductive and osteoinductive performances of titanium-based implants. Smart wound patches and polymeric gels functionalized with antimicrobial and wound healing biomolecules incorporated within micro- and nanoparticles constitute the purpose of the “Medical devices (patches and gels) based on composite biomaterials obtained by laser, plasma and radiation technologies and alternatives for enhanced healing of cutaneous injuries” subproject. The “Technologies based on magnetic triggered nanostructures for oncological therapy: early diagnosis and targeted treatment” subproject aims the development of multifunctional medical devices for specific and selective diagnosis and treatment of breast cancer and melanoma. The general impact of the TERAMED project ensues from the beneficial conjunction of the clinical potential of the proposed medical devices, the feasible technological transfer and the economic advantages of interinstitutional collaboration.

In vitro evaluation of potential biomedical strategies aimed to prevent bone loss during space flight Call name:
2017 - 2018

Role in this project: Key expert

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); INSTITUTUL DE STIINTE SPATIALE (RO)

Affiliation: INSTITUTUL DE BIOCHIMIE (RO)

Project website: http://www.biochim.ro/grant-8-spacebone/

Abstract:

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: Key expert

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.

Miniaturized bio-platform for simultaneous melanoma combination therapy and tumorigenicity screening Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2016-1628 2017 - 2018

Role in this project: Key expert

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)

Affiliation: INSTITUTUL DE BIOCHIMIE (RO)

Project website: http://lspi.inflpr.ro/2017/PED/PED131/Home.html

Abstract:

Cancer is among the major causes of mortality nowadays, estimations provided by the World Health Organization revealing that its incidence is expected to increase by about 70%, up to 22 million cases, during the next two decades. Melanoma is the most aggressive skin cancer due to its high multi-drug resistance, frequent relapse and decreased survival rate. All major therapies, including chemo-, immuno-, and radio-therapies have failed to increase patients survival rates significantly due to a complex interplay of genetic, host, and environmental factors. It was recently evidenced that tumour cells may exhibit ‘plasticity’ in response to microenvironmental cues. The geometric features of cell-matter interface may influence a population of cells that can guide cancer cells towards a stem-cell-like state. The goal of this project proposal is to design, fabricate and test the performances of a miniaturized bioplatform that will simultaneously address two objectives: i) the synergistic co-targeting of melanoma cells by a precise mixture of signaling path inhibitors and epigenetic modulators; and ii) the evaluation of cells tumorigenicity guided by the geometric features of the patterns assembled on substrates. One pot laser technique Combinatorial Matrix Assisted Pulsed Laser Evaporation will be applied through specific designed masks to develop bioplatforms with innovative configurations. Several in vitro assays will be performed to evaluate biochips performances against different melanoma cell lines, while melanocytes and dermal fibroblasts will be used as controls. Moreover, in order to reproduce the in vivo environment and interactions, we will grow spheroids (mini-tumors) on the laser-fabricated patterns. Such mini-bio-labs that combine smart materials and cell-instructive interfaces could push forward advances in combination cancer therapy, new drugs formulations and hopefully personalized therapeutic strategies.

Multiscale bone-like intelligent interfaces engineering using laser methods for mesenchymal stem cells enhanced osteoinduction Call name: Projects for Young Research Teams - RUTE -2014 call
PN-II-RU-TE-2014-4-2434 2015 - 2017

Role in this project: Key expert

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)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE DEZVOLTARE PENTRU FIZICA LASERILOR, PLASMEI SI RADIATIEI - INFLPR RA (RO)

Project website: http://ppam.inflpr.ro/TE_24/biosintel_ro.htm

Abstract:

BIosINTEL project aim is engineering smart bio-interfaces with multiple and synergetic functionalities for effective controlled regulation of stem cell differentiation and low inflammatory response for enhanced osseointegration. The innovative strategy within the project proposed is:

-Smart surface design: Bone like multiscaled microstructured surfaces(concave pits with various curvatures,depths, diameters and pits density on the surface) obtained by grey level masks assisted excimer laser processing technique

-Innovative hierarchical nanostructuring of the bone like microstructured surfaces by tailoring the self assembling of elastomeric polypeptides and biodegradable Poly-caprolactone copolymers spherulites formation

-Specific laser based functionalization by i)tethering active factors (elastin) within the biodegradable smart copolymer matrix (by single step matrix assisted pulsed laser evaporation) and ii)selective patterning of 2d and 3d bio-clusters as nucleation centers for mineralization (by laser induced forward transfer)

-Effective use of hierarchically patterned topography for tuning biointerface characteristics to i) stem cell differentiation, ii) modulate fibrous tissue formation/ tissue encapsulation, iii) extending the designed bone like topography toward implants (Ti and Zr alloy)

The design model based on tailored topographical and chemical cues for quantifying the steering of stem cell has impact in basic cell researches and tissue engineering application.

Identification of the Cellular and Molecular Profile of Endometriosis as a Means to Develop New Individualized Therapeutic Procedures and ith Predictive Role for Infertility Call name: Joint Applied Research Projects - PCCA 2013 - call
PN-II-PT-PCCA-2013-4-1348 2014 - 2017

Role in this project: Key expert

Coordinating institution: UNIV.DE MEDICINA SI FARMACIE - CAROL DAVILA

Project partners: UNIV.DE MEDICINA SI FARMACIE - CAROL DAVILA (RO); INSTITUTUL DE BIOCHIMIE (RO); GINMED CITY SRL (RO)

Affiliation: INSTITUTUL DE BIOCHIMIE (RO)

Project website: http://www.endofertil.ro

Abstract:

Endometriosis is a benign condition of the female reproductive tract characterized by the implantation of endometrial tissue outside the uterine cavity. The two main manifestations of this disease are chronic pelvic pain of variable intensity and infertility. The disease is a significant source of morbidity among women of reproductive age (with an estimated prevalence of 5-15% in this group), being responsible for approximately 30% of all cases of infertility. Endometriosis is a pervasive condition, with a variable and often unpredictable response to the currently-available palette of therapeutic strategies. More than 70% of patients diagnosed with endometriosis suffer one or more recurrences during their lifetime, which often have a negative impact on the patients’physical and psychological well-being. The socio-economic burden of the disease is impressive: impairment of work capacity, sick leave, high costs of treatments and the frequent use of assisted reproductive techniques to achieve pregnancy lead to a diminished quality of life for many women.

Although several theories regarding the aetiology of endometriosis have been put forth, none of them has been able to explain every aspect of this disease so far. Recent research has shed light on the importance of the immunologic and molecular profile of the endometrium in the pathogenesis and course of the disease. Key elements are the responsiveness of the endometrium to ovarian hormones, its immunophenotype and its potential for aggression and invasion.

EndoFertil is a project that addresses the role of these three important parameters as potential markers for the staging of endometriosis, the fertile potential of the woman and the estimation of the disease’s response to hormone therapy. These parameters have been investigated separately in both eutopic and ectopic endometrium; however, no comparisons between samples of eutopic and ectopic endometrium prelevated from the same woman exist. This important element of novelty brought forth by this project has the advantage of opening avenues for fundamental research with regard to the molecular mechanisms involved in the pathogenesis of the disease.

The best course of treatment that improves both fertilization outcomes and the quality of life of patients is a source of continued debate. EndoFertil’s principal aim is to develop a highly efficient clinical and therapeutic protocol for the control of symptoms, preservation of fertility and prevention of recurrences. This will be done by personalizing the treatment regimen according to the levels of the above-mentioned cellular and molecular markers. Patient follow-up will determine the success of this approach and the benefit of instituting such a protocol on a national and, subsequently, international level.

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: Key expert

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: INSTITUTUL DE BIOCHIMIE (RO)

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.

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: Partner team leader

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.

Study of melanoma antigen Tyrosinase Related Protein-2 in metastatic progression-possible implications in diagnosis and therapy of malignant melanoma Call name: Exploratory Research Projects - PCE-2011 call
PN-II-ID-PCE-2011-3-0492 2011 - 2016

Role in this project: Key expert

Coordinating institution: Institutul de Biochimie al Academei Romane

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

Affiliation: Institutul de Biochimie al Academei Romane (RO)

Project website: http://www.biochim.ro/ib/projects/melanoma-trp2/melanoma-trp2.php

Abstract:

Cutaneous malignant melanoma (CMM) is defined by the transformation of skin melanocytes in tumor (melanoma) cells rapidly proliferating at sites of distal organs and eventually causing death. CMM has insidious evolutions, is often misdiagnosed and therapeutically resistant. The molecular mechanisms responsible for CMM development and progression are only beginning to be appreciated.

Tyrosinase Related Protein-2 is expressed in both melanocytes and melanoma cells. TRP-2 catalyses a distal step in melanogenesis, is a melanoma antigen and its derived peptides are used in anti-melanoma therapy. TRP-2 mediates a novel antiapoptotic pathway induced by therapeutic stress in melanoma.

The present grant proposal aims to investigate: a) TRP-2 expression and association with other melanoma antigens and prognostic markers in human melanocytic lessions in order to introduce TRP-2 as an adjunct and possibly as a prognosis marker in the evaluation of melanocytic lesions; b) the in depth regulatory factors (cellular and structural) and molecular mechanisms of TRP-2 maturation, trafficking and degradation in human melanoma cell lines (primary and metastatic) which will provide additional information in understanding melanoma progression; c) the TRP-2 interacting partners, representing potential drug-targets of the antiapoptotic TRP-2-mediated pathway. The studies are expected to generate knowledge from fundamental approaches with further implications in melanoma diagnosis and therapy.

Cellular mechanisms associated with the endoplasmic reticulum during hypoxia. Implications for biomedical research. Call name: Projects for Young Research Teams - TE-2010 call
PN-II-RU-TE-2010-0048 2010 - 2014

Role in this project: Key expert

Coordinating institution: INSTITUTUL DE BIOCHIMIE DIN BUCURESTI

Project partners: INSTITUTUL DE BIOCHIMIE DIN BUCURESTI (RO)

Affiliation: INSTITUTUL DE BIOCHIMIE DIN BUCURESTI (RO)

Project website: http://www.biochim.ro/ib/projects/hipoxia/hipoxia_ro.php

Abstract:

ALL CELLS, IN PARTICULAR THE EUKARYOTES, DEPEND FOR THEIR SURVIVAL ON AN ADEQUATE SUPPLY OF OXYGEN. HYPOXIA CAN AFFECT THE WHOLE BODY IF ORGANISM ENCOUNTERS CARDIAC ARREST OR SEVERE HYPOTENSION, OR A SMALLER TISSUE AREA AS IN MYOCARDIAL INFARCTION, STROKE OR CANCER. IF OXYGEN CONCENTRATIONS ARE VERY LOW AND PROLONGED FOR LONG TIME CELLS ENTER APOPTOSIS AND WILL FINALLY DIE. SO FAR MANY STUDIES FOCUSED ON THE MECHANISMS OF OXYGEN SENSING AND ON ALTERATIONS OF CYTOPLASMIC AND MITOCHONDRIAL PROCESSES DURING HYPOXIA. RECENT FINDINGS SUGGEST THAT AN ENDOPLASMIC RETICULUM (ER) ASSOCIATED PROCESS, NAMELY THE UNFOLDED PROTEIN RESPONSE (UPR) IS ACTIVATED DURING HYPOXIA LEADING TO FORMATION OF TRANSCRIPTION FACTORS THAT DRAMATICALLY EFFECTS GENE EXPRESSION AND REGULATION. HOWEVER, THE TRIGGER THAT PROMOTES UPR ACTIVATION IS UNKNOWN. USING COMPLEX CELLULAR BIOLOGY, BIOCHEMISTRY AND MOLECULAR BIOLOGY ASSAYS, WE AIM TO INVESTIGATE DISULFIDE BOND FORMATION FOR SEVERAL MODEL PROTEINS DESTINED TO THE SECRETORY PATHWAY AND SUBSEQUENTLY TO IDENTIFY THE ER RESIDENT PROTEINS THAT CAN NOT FUNCTION PROPERLY IN HYPOXIC CONDITIONS. ER ASSOCIATED DEGRADATION (ERAD) MAY ALSO BE THE CAUSE OF UPR ACTIVATION. FOR THIS REASON, WE WILL MONITOR DEGRADATION OF SEVERAL ERAD SUBSTRATES IN HYPOXIA, AIMING TO UNDERSTAND IF ACCUMULATION OF ERAD SUBSTRATES IS THE LEADING CAUSE OF UPR ACTIVATION. ALL TOGETHER THESE FINDINGS WILL CREATE NEW POTENTIAL TARGETS FOR MEDICINES THAT AIM TO ALLEVIATE THE SYMPTOMS OF HYPOXIA-ASSOCIATED DISEASES OR WILL INTERFERE WITH ACTIVATION OF SPECIFIC GENES IN CANCER.

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