BrainMap

Violeta Anca Gafencu

PhD

- INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU''

Researcher | Scientific reviewer

Web of Science ResearcherID: ID: 6506192688

Curriculum Vitae (03/03/2020)

Expertise & keywords

A novel anti-atherosclerotic chimeric protein that impedes the infiltration of the inflammatory cells in the vessel wall Call name: P 4 - Proiecte de cercetare exploratorie - PCE-2021
PN-III-P4-PCE-2021-1755 2022 - 2024

Role in this project: Project coordinator

Coordinating institution: INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU''

Project partners: INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU'' (RO)

Affiliation:

Project website: http://www.icbp.ro/static/en/en-networking_grants-grants-national_grants/fastrap.html

Abstract:

Cardiovascular diseases are the leading causes of mortality. Atherosclerosis is a disease of the arteries, characterized by the formation of the atheromatous plaque that limits blood flow. The inflammatory aspect of atherosclerosis includes the activation of the endothelium which begins to express adhesion molecules such as VCAM-1 and the infiltration of the immune cells in the vessel wall. Here we aim to induce the death of the immune cells infiltrating in the atherosclerotic plaque by the local and selective lentiviral delivery of a therapeutic gene encoding a chimeric protein consisting of two main parts: VCAM-1 binding peptide (VBP) for anchoring and soluble FasL, as an apoptotic trigger. VBP will ensure the clustering and oligomerization of FasL at the surface of the activated endothelium allowing the interaction with the Fas receptor expressed on the inflammatory cells infiltrating in the atheromatous plaque. This interaction will induce apoptosis of the infiltrating immune cells, will reduce the foam-cell formation in the plaque, and will arrest the progression of atherosclerosis. The development of this strategy by the present project will open new horizons and opportunities for the treatment of inflammatory diseases. We expect our novel therapy to show high efficacy, and most importantly, less severe side effects due to selective targeting. Our targeted treatment would provide a clear social and economic benefit due to increased survival and better quality of life.

Integrative Personal Omics Profiles in Glioblastoma Recurrence and Therapy Resistance Call name: P 3 - SP 3.2 - Proiecte ERA.NET - COFUND
COFUND-PERMED-PerProGlio 2019 - 2022

Role in this project: Partner team leader

Coordinating institution: INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU''

Project partners: INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU'' (RO); Philipps-Universität Marburg (DE); University of Freiburg (DE); IRCCS Ospedale San Raffaele (IT); Hospital Universitario y Politécnico La Fe (ES); University of Toronto (CA)

Affiliation: INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU'' (RO)

Project website: http://www.icbp.ro/static/en/en-networking_grants-grants-international/perproglio.html

Abstract:

Glioblastoma (GBM) as most common aggressive brain tumor has a poor prognosis and median survival times of
We propose to use our combined expertise of multiple “OMICS” methods to dissect individual parameters that determine recurrence and therapy resistance in GBM with possible therapeutic implications. Initially, we will use a retrospective cohort of 100 patients with clinical metadata of GBM primary and recurrent samples. Abundance-based biomarkers associated with time-to-recurrence and therapy resistance will be obtained by analyzing extracellular vesicles (EVs) with respect to proteolytic fragments (mass spectrometry based), protease activities, and miRNA content. In addition, a full NGS analysis will be performed to characterize recurrence in individual patients and combine “OMICS” with clinical and imaging data. From these analyses, we aim to identify personalized easy-to-access biopsy markers so that investigation of pre- and post-surgery serum samples (at time of initial surgery) allows to faithfully discern tumor-originating molecules through their decreased abundance in post-surgery samples. We further hypothesize that multimodal monitoring, e.g. combining imaging data with molecular markers allows to establish a molecular signature of GBM recurrence which is particularly powerful for reliable prediction of GBM recurrence in a prospective patient cohort.

Apolipoprotein A-II derived peptides with anti-atherosclerotic potential Call name: P 1 - SP 1.1 - Proiecte de cercetare pentru stimularea tinerelor echipe independente
PN-III-P1-1.1-TE-2019-2044 2020 - 2022

Role in this project: Key expert

Coordinating institution: INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU''

Project partners: INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU'' (RO)

Affiliation: INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU'' (RO)

Project website: http://www.icbp.ro/static/en/en-networking_grants-grants-national_grants/a2a.html

Abstract:

Apolipoprotein A-II (apoA-II) is the second most abundant protein of the anti-atherosclerotic high-density lipoprotein (HDL). Despite its higher affinity for lipids than ApoA-I, apoA-II overexpression in mice induced displacement of certain HDL components and did not improve HDL functionality. Our hypothesis is that apoA-II derived-peptides improve HDL anti-atherosclerotic properties. The rationale of this hypothesis is that apoA-II truncations eliminate the negative effects of apoA-II overexpression while retains high lipid affinity, leading to HDL lipid enrichment. Thus, this project aims to improve HDL functionality and to enhance its beneficial effects, not to increase HDL amount. The goal of this project is to identify an apoA-II domain which, by its involvement in lipid metabolism, improves HDL functionality in atherosclerosis therapy. To this aim, we envision two main objectives: (O1) Generation of recombinant adenoviruses encoding apoA-II-derived peptides (corresponding to the apoA-II domains) and the full-length apoA-II; (O2) Evaluation of apoA-II fragments ability to regress the atherosclerotic plaque in a mouse atherosclerosis model. To accomplish these objectives, we take the advantage that we already have cloned the apoA-II fragments in the adenoviral vector. To obtain the adenoviruses we will: (1.1) recombine the apoA-II-containing vectors with the plasmid encoding the viral components, (1.2) package the adenovirus in AD-293 cells, (1.3) amplify the adenoviruses, (1.4) purify them by ultracentrifugation and (1.5) determine its titre. After in vivo transduction of truncated apoA-II forms in atherosclerotic mouse model, we plan to analyse: (2.1) the plasma cholesterol and triglyceride levels; (2.2) lipoproteins fractions (2.3) cholesterol efflux ability of HDL from transduced mice; (2.4) the atherosclerotic plaque evolution in the aorta of the transduced mice. The data obtained may open up new avenues for developing novel anti-atherosclerotic therapies

Demonstration of the enhanced anti-atherosclerotic potential of apolipoprotein E targeted to the activated endothelium by fusion with VCAM-1 binding peptide Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2019-4574 2020 - 2022

Role in this project: Project coordinator

Coordinating institution: INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU''

Project partners: INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU'' (RO)

Affiliation: INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU'' (RO)

Project website: http://www.icbp.ro/static/en/en-networking_grants-grants-national_grants/vapo.html

Abstract:

Atherosclerosis is the first contributor to the cardiovascular disease, the main cause of mortality. ApolipoproteinE (apoE) is an atheroprotective molecule that facilitates cholesterol efflux. APOE deletion or malfunction leads to atherosclerosis in mice and humans. The hypothesis of the project is that increasing the local concentration of apoE3 in the lesion prone areas or at the site of atheroma will prevent, reduce or retard the plaque formation. The goal of this project is to drive the selective expression in the atheromatous site of a chimeric apoE –based protein, possessing not only the cholesterol efflux functions but also an anchor to the activated endothelial cells to trap apoE in the atherosclerotic site. This will be achieved by generating a lentivirus carrying a chimeric molecule formed by a binding peptide for vascular cell adhesion molecule-1 (VCAM-1-BP) and apoE expressed under the control of VCAM-1 promoter. VCAM-1-BP serves as targeting moiety to VCAM-1 expressed on the endothelium of atheroma, and apoE serves as effector moiety that induces the cholesterol efflux from the lipid-loaded cells. Expression of the chimeric protein under the control of the VCAM-1 promoter takes advantage of the inherent upregulated VCAM-1 promoter in atheroma. The targeted apoE expression in the lesion prone areas is expected to prevent or regress the atherosclerotic process, without any side effects associated with a systemic expression. To this aim, we have 3 objectives: (i) constructing the plasmid encoding the fusion protein under VCAM-1 promoter; (ii) packaging the lentivirus that will specifically induce the expression of the fused protein; (iii) testing the functionality of the apoE-VCAM-1-BP in an atherosclerotic mouse model. Successful conclusion of the proposed approach may open new therapeutic tools for atherosclerosis, but also for other diseases where inflammation and apoE play a pivotal role in the progression of the pathology, such as Alzheimer’s disease.

Intelligent therapies for non-communicable diseases based on controlled release of pharmacological compounds from encapsulated engineered cells and targeted bionanoparticles Call name: P 1 - SP 1.2 - Proiecte complexe realizate in consorții CDI
PN-III-P1-1.2-PCCDI-2017-0697 2018 - 2021

Role in this project: Key expert

Coordinating institution: INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU''

Project partners: INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU'' (RO); UNIVERSITATEA POLITEHNICA DIN BUCURESTI (RO); INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA MATERIALELOR BUCURESTI RA (RO); INSTITUTUL DE CHIMIE MACROMOLECULARA "PETRU PONI" (RO)

Affiliation: INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU'' (RO)

Project website: http://www.icbp.ro/static/en/en-networking_grants-grants-national_grants/intera.html

Abstract:

Non-communicable diseases (atherosclerosis, diabetes, obesity), a major cause of mortality, are characterized by associated inflammatory processes. The complex project INTERA aims to develop innovative therapeutic methods to ameliorate the pathological progression by reducing the inflammatory process. The multidisciplinary studies proposed by INTERA can create and define new nano- or micro-medical devices usable for smart and innovative anti-inflammatory therapies. INTERA includes 4 projects: (1) Encapsulation of genetically manipulated eukaryotic cells for controlled release of pharmacologically active products; (2) Development of a 3D platform designed for pre-clinical drug testing composed of cells incorporated into three-dimensional bio-matrices; (3) Intelligent nanobioparticles designed for bioactive compounds vectoring to pathological sites for vascular inflammation targeting. (4) Polymeric conjugates for efficiently inducing the expression of genes of interest with applicability in cellular therapy. The consortium consists of 4 partner research units - two institutes of the Romanian Academy (IBPCNS, ICMP), a university (UPB) and a national CD Institute (INCDFM) with good territorial coverage (Bucharest-Ilfov-Iasi). Predicted Indicators: 10 new R & D jobs, 8 ISI articles, 4 patent applications, 8 new technologies, 7 new service offers posted on the ERRIS platform. Institutional development: the new competences and the improvement of existing ones in partner units will attract the attention of the economic environment towards a better correlation of scientific and economic interests and better valorization in the field of drug science. From a social point of view, institutional development will lead to lowering the cost of these pathologies through new therapeutic approaches, more accessible to the population and hence, improving the quality of life.

Improve institutional competitiveness in the field of type 1 diabetes by developing an innovative concept of immunotherapy based on mesenchymal stromal cells Call name:
P_37_668 2016 - 2020

Role in this project: Key expert

Coordinating institution: INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU''

Project partners: INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU'' (RO)

Affiliation: INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU'' (RO)

Project website: http://www.icbp.ro/static/en/en-networking_grants-grants-international/diabeter.html

Abstract:

Combined hormonal treatment-induced gene transactivation of anti-atherosclerotic proteins as an innovative therapeutic approach for atherosclerosis Call name: Projects for Young Research Teams - RUTE -2014 call
PN-II-RU-TE-2014-4-2660 2015 - 2017

Role in this project: Key expert

Coordinating institution: INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU''

Project partners: INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU'' (RO)

Affiliation: INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU'' (RO)

Project website: http://www.icbp.ro/static/en/en-networking_grants-grants-national_grants/aterte.html

Abstract:

Cardiovascular disease causes more that 55% of all deaths in Europe, hyperlipidaemia being a major contributor. The apolipoproteins have an important role in lipid metabolism. The goal of this proposal is to determine the fine tuning of the apolipoprotein (E, AI and CII) gene regulation by the estrogen/thyroid hormones, in order to reduce the atherosclerotic process. To this, the main objectives are: 1.To identify the molecular mechanisms involved in apolipoprotein gene regulation by estrogen / thyroid hormones. For this we plan to i) localization of the regulatory elements responsible for apolipoprotein gene modulation by estrogen/thyroid hormones, ii) test the interaction of ERs/TRs with other factors and assess their role in apolipoprotein gene regulation, iii) assess the effects of the endocrine disruptors on apolipoprotein expression by estrogen / thyroid hormones; 2. To determine the beneficial effects of combined hormonal treatments in experimental atherosclerosis, by i) assessment of the effects of combined hormonal treatments on lipid plasma levels in normal/atherogenic mice, ii) evaluation of apolipoprotein gene modulation and investigation of atherosclerotic plaques development in mice receiving combined hormonal treatments. The result will elucidate the gene regulatory mechanisms of anti-atherosclerotic apolipoproteins by estrogen/thyroid hormones, and will reveal the link between hormonal imbalance and dyslipidaemia, with clinical applications.

Genetically engineered apolipoproteins immobilized on nanoparticles: a Molecular Trojan horse targeting atherosclerotic plaque Call name: Projects for Young Research Teams - RUTE -2014 call
PN-II-RU-TE-2014-4-2143 2015 - 2017

Role in this project:

Coordinating institution: INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU''

Project partners: INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU'' (RO)

Affiliation: INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU'' (RO)

Project website: http://www.icbp.ro/static/en/en-networking_grants-grants-national_grants/apgen.html

Abstract:

Apolipoprotein E (apoE) plays a pivotal role against atherosclerosis. This role is exerted only by apoE delivered at the lesion level. The main aim of this project is to obtain apolipoprotein-fullerene based nano-systems (AFN) targeted toward the atherosclerotic plaque through transferrin receptor. The transferrin or anti-transferrin receptor monoclonal antibody included in AFN will facilitate their transcytosis through the endothelial layer and will enhance their binding on the macrophage-foam cells. We plan to achieve the following objectives: (1) Setting up a series of AFNs using recombinant apoE3 or apoE3-HRP chimera alone or together with transferrin or with anti-transferrin receptor monoclonal antibodies; (2) Biochemical characterization of the obtained AFNs by size, apolipoprotein/Tf or TfRMoAb ratio, lipid binding capacity; (3). Functional characterization: (i) In vitro tests of the capacity of AFNs to cross the endothelial layer, to bind on macrophage surface and to participate in the cholesterol efflux from the macrophage-foam cells; (ii) In vivo AFNs ability to reduce the atherosclerotic plaques in animal models. Targeting apoE at the plaque using novel biotechnologies will provide an efficient cholesterol efflux from the lipid loaded cells, having significant anti-atherosclerotic benefits. This strategy may open new horizons for developing “synthetic lipoproteins” based on recombinant proteins attached to spherical nanoparticles for diverse therapeutic purposes.

Apolipoprotein E-based novel anti-atherosclerosis cell-therapy approaches Call name: Exploratory Research Projects - PCE-2011 call
PN-II-ID-PCE-2011-3-0591 2011 - 2016

Role in this project:

Coordinating institution: Institutul de Biologie si Patologie Celulara "Nicolae Simionescu"

Project partners: Institutul de Biologie si Patologie Celulara "Nicolae Simionescu" (RO)

Affiliation: Institutul de Biologie si Patologie Celulara "Nicolae Simionescu" (RO)

Project website: http://www.icbp.ro/static/en/en-networking_grants-grants-national_grants/pniiidpce201130591.html

Abstract:

Apolipoprotein E (apoE) is an athero-protective molecule, playing a pivotal role in lipid metabolism. The goal of the project is to induce an increased apoE expression in monocytes and endothelial cells (EC) in order to prevent or regress the atherosclerotic process. We have 3 objectives: 1. To identify the transcriptional mechanisms leading to activation of apoE expression. We will (1a) investigate transcriptional regulation of apoE gene in monocyte and macrophages. (1b) induce upregulation of apoE gene in endothelial cell. 2. To target apoE expressing monocytes at the atherosclerotic plaques. We plan to (2a)induce ex vivo apoE expression in monocytes; (2b)test the minimal monocyte activation that allows the most efficient infiltration in atheroma; (2c)transplant apoE expressing monocytes in apoE null mice and follow plaque regression. 3. To generate a tissue specific transgenic mouse model that expresses apoE specifically in the endothelium and to asses its sensitivity to atherosclerosis. We will (3a)obtain transgenic mice with inducible endothelial-specific expression of apoE3; (3b)assess the association between EC-secreted apoE and different lipoproteins; (3c)determine the ability of EC-secreted apoE to reach the subendothelial space; (3d)evaluate the regression of the atherosclerotic plaques in mice expressing apoE3 in EC. The project will lead to novel apoE based anti-atherosclerotic treatments and will open new horizons for developing cell-specific base therapies.

Biologically inspired systems for engineered structural and functional entities Call name: Complex Exploratory Research Projects - PCCE-2011 call
PN-II-ID-PCCE-2011-2-0028 2012 - 2016

Role in this project: Key expert

Coordinating institution: "Petru Poni" Institute of Macromolecular Chemistry

Project partners: "Petru Poni" Institute of Macromolecular Chemistry (RO); "Petru Poni" Institute of Macromolecular Chemistry (RO); "Petru Poni" Institute of Macromolecular Chemistry (RO); "Petru Poni" Institute of Macromolecular Chemistry (RO); "N. Simionescu" Institute of Cellular Biology and Pathology (RO); " Gheorghe Asachi" Technical University of Iasi (RO); " Costin D. Nenitescu" Institute of Organic Chemistry (RO)

Affiliation: "N. Simionescu" Institute of Cellular Biology and Pathology (RO)

Project website: http://www.intelcentru.ro/Biomimetics_PCCE

Abstract:

The project aims to study, to develop and to preliminary test biomimetic structural and functional entities, able to act as gene transfection vehicles of non-viral type, and having a DNA packaging capacity of about 2  5 kilobases. The main features of these entities are: (i) the general structure of a polyplex, (ii) the functionality of a cargo-complex that chemomimic the histones, morphomimic the nucleosome and biomimic a virus like gene vector, (iii) the ability to include or to reversibly bind and transport (bio)chemical species necessary to assist the DNA vehiculation and trafficking, (iv) are based on fullerene-rich polymers and / or dendrimers, (v) the capacity to associate to artificial extracellular matrices, in order to generate gene delivery systems with transfection ability, for ex vivo applications. The developed entities will represent effective tools in genetic and tissue engineering, useful in health restoration, life quality enhancement, and to cure tissue and human organism deficiencies. The envisioned engineering strategy to build biomimetic entities may sustain a spin-off type transfer of knowledge towards hi-tech application areas, with a clear echo in clinics and, finally, in human health. The project involves seven complementary teams hosted by four research and academic institutions. In equilibrated ratios, senior, young and junior researchers will collaborate inside the project frame.

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