BrainMap

Mrs. Anca Botezatu

Dr.

- INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU"

Researcher | Scientific reviewer | PhD supervisor

Web of Science ResearcherID: not public

Curriculum Vitae (12/06/2025)

Expertise & keywords

Development of anticancer nanoparticulate systems based on novel metal complexes Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2019-5143 2020 - 2022

Role in this project:

Coordinating institution: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU"

Project partners: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO); UNIVERSITATEA DE MEDICINA SI FARMACIE "CAROL DAVILA" (RO)

Affiliation: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO)

Project website: https://www.virology.ro/ro/cercetare/proiecte/proiect-ped-383-2020

Abstract:

A new generation of efficient metal-based drugs needs to be developed in order to overcome the biological, biopharmaceutical and biomedical drawbacks of standard chemotherapy. Use of metallo-drugs in cancer treatment has been hampered by an indaquate pharmacokinetic profile that limited the access to the biological target. This has led to the development of novel technologies based on nanostructured materials, acting as vectors for metallodrug delivery or simply as protectors of active species of the complexes for amplifying their activities and reducing their degradation. The aim of the project is to develop and validate new liposomal systems for transport and delivery of 2 promising anticancer agents previously studied by our research group. Nanoparticulate drug carrier systems will improve the therapeutic effectiveness and safety profile of these novel anticancer agents. The efficiency of these nanoformulations will be evaluated in terms of stability, drug entrapment efficiency, release behaviour, cell uptake, cytotoxicity, farmacotoxicology and pharmacokinetics. The project specific objectives are: 1) Development of liposomal systems validated at the laboratory level with novel anticancer agents; 2) Estimation the in vitro biological activity of the liposomal systems on various cell lines, including drug resistant cell lines, identifying biomarkers involved in modulating their biological activity; 3) Estimating the pharmaco-toxicological and pharmacokinetic profile of liposomal systems. Nanoparticles provide an enhanced bioavailability, in vivo stability, intestinal permeability, solubility, sustained and targeted delivery, therapeutic effectiveness of the anticancer drugs. The proposed project is a complex, interdisciplinary study related to biomedical international research, that aims to intends to transform modern methods, worldwide used in pharmacological, immunological and molecular biology studies, in instruments used for the translation to oncology.

Artificial Intelligence Algorithms in Male Infertility Diagnosis Based on New Molecular Approaches Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2019-4402 2020 - 2022

Role in this project:

Coordinating institution: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU"

Project partners: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO); INSTITUTUL NATIONAL DE ENDOCRINOLOGIE "C.I.PARHON" BUCURESTI (RO); NET - CONNECT BUSINESS SUPPORT SRL (RO)

Affiliation: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO)

Project website: https://www.virology.ro/en/research/projects/male-infertility

Abstract:

Causes of male infertility were reported as mainly Y chromosome deletions. However only 10-15 % of infertile patients shows such anomalies. Studies regarding infertility expanded from the genetic level to epigenetic factors. The proposal aims to improve investigation protocols and diagnosis for male infertile patients. This scope will be achieved through developing a method for epigenetic profiler (panel) which will evaluate the level of methylation for selected genes involved in male infertility and to develop a decision support system (DSS) based on artificial intelligence (AI) that can predict the results a from a questionnaire, hormonal profile, infection status, methylation panel and semen analysis. The novelty of current proposal is to elaborate a new protocol and AI based algorithms to investigate infertile men, not only to diagnose, but to improve the selection for assisted reproduction techniques (ART). Such investigations, protocols are not introduced yet in the current practice worldwide, and are the subject of great interest for researchers and especially for clinicians who expect validating and transferring research results into the clinic as soon as possible. Despite the fact that the number of clinics performing assisted reproductive procedures is high, the success rate is low due to lack of opportunities for testing at the molecular level functionality sperm and oocytes.

Considering the team's experience in terms of experimental methods to be used in this project and the conceptual coherence supported by papers published in this field in recent years, along with the existent infrastructure, we believe that the project has a high feasibility to achieve the proposed goals in good conditions.

ND10 bodies dynamic switch in viral chromatin remodeling during early hrHPV infection. Call name: P 1 - SP 1.1 - Proiecte de cercetare pentru stimularea tinerelor echipe independente
PN-III-P1-1.1-TE-2019-1759 2020 - 2022

Role in this project:

Coordinating institution: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU"

Project partners: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO)

Affiliation: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO)

Project website: http://www.virology.ro/en/research/projects/early-hrhpv-infection

Abstract:

Human papilloma viruses (HPVs) are non-enveloped double-stranded DNA genome viruses, divided according to oncogenic potential into low-risk (lrHPV) and high-risk (hrHPV) genotypes for which persistent infection is associated with cervical dysplasia and carcinogenesis. HPVs developed strategies to interfere with innate immune responses, to delay adaptive immune responses and thus to promote oncogenesis. Even if the HPV viral life cycle has been extensively studied, the regulatory proteins that influence viral chromatin and interactions of the viral DNA with complex nuclear structure in the infected cells are still under investigation. The proposal intends to unveil the mechanism of how hrHPV optimizes its own transcription in order to evade the intrinsic immune response being prone to use epigenetic mechanisms to regulate biological activities during virus life cycle.

In this context, we hypothesize an association between HPV genome and chromatin remodeling complexes interaction that influences the early viral gene transcription. In order to highlight this we propose the following specific objectives: identifying ND10 components involved in chromatin remodeling complexes and histone chaperones during early viral infection using as experimental models infected human cell lines with HPV16/18 pseudovirions; establishing if ND10 complex has a role in intrinsic immune response in hrHPV infection; discovering the role of histone H3.3 in viral chromatin status during first stages of infection (HPV and ND10 co-localization); understanding which viral factors may play a role in regulation of ND10 chromatin remodelers, which may help the virus escape from intrinsic immunity mechanism.

The obtained data will enrich the knowledge in the field of molecular biology and epigenetics of the HPV infection, which may represent a future challenge for developing new therapeutic targets and strategies in disease management. This may open new research direction for HPV–induced tumorigenes

The role of E6/E7 HPV16 oncogenes in chromatin remodelling through components of NuRD complex(MBD2, MBD3) Call name: Projects for Young Research Teams - RUTE -2014 call
PN-II-RU-TE-2014-4-2502 2015 - 2017

Role in this project:

Coordinating institution: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU"

Project partners: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO)

Affiliation: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO)

Project website: http://www.virology.ro/en/research/projects/the-role-of-e6-e7-hpv16-oncogenes

Abstract:

Cervical cancer is the third most commonly diagnosed type of cancer and one of the most frequently occurring malignant tumors in women worldwide. Human papilloma virus (HPV) is considered the etiologic agent of cervical neoplasia. The transforming potential of high risk human papillomavirus (hrHPV) is due to E6 and E7 viral oncoproteins. Persistent hrHPV infection leads to changes in the host genome and epigenome. The control of gene expression is complex and involves epigenetic changes (DNA methylation, histone modification, miRNAs activity). The nucleosome remodeling and deacetylation complex (NuRD) is a group of associated proteins with ATP-dependent chromatin remodeling and histone deacetylase activities. MBD2 and MBD3 proteins from NuRD complex exhibit methyl-CpG-binding domains (MBD), which mediate an interaction with methylated DNA. At molecular level, MBD2 binds to methylated DNA (at 5-methylcytosine -5 mC), while MBD3 binds to DNA at 5-hydroxymethylcytosine (5 hmC).

Given the increasing data regarding the MBD2 and MBD3 functional differences and similarities, the proposal aims to assess the viral oncogenes influence on the MBDs overall binding pattern to CpG islands from promoters, gene control region, enhancers, gene bodies. The resulting data will help to elucidate the mechanisms leading to oncogenesis and to identify new potential therapeutic targets.

Implementation of a complex genome profiling diagnostic algorithm for patients with congenital and developmental abnormalities Call name: Joint Applied Research Projects - PCCA 2013 - call
PN-II-PT-PCCA-2013-4-2240 2014 - 2017

Role in this project:

Coordinating institution: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU"

Project partners: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO); INSTITUTUL NATIONAL PENTRU SANATATEA MAMEI SI COPILULUI "ALESSANDRESCU-RUSESCU" BUCURESTI (RO); UNIVERSITATEA DE MEDICINA SI FARMACIE "GR. TH. POPA" (RO); PERSONAL GENETICS S.R.L. (RO)

Affiliation: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO)

Project website: http://www.virology.ro/ro/congen-proiect

Abstract:

The proposed project will set up a consortium in genomics, aiming at the implementation of new investigation methods in clinical practice that could contribute to the elucidation of the molecular mechanisms of congenital and developmental abnormalities with a final practical goal in prophylaxis and better clinical management of patients. The project corresponds to the direction 4 - HEALTH and its objectives refer to the national implementation of new prevention and intervention methods in accordance with European standards (4.1.6). The major objectives of the project are:

1) Investigation of genetic abnormalities in Romanian patients with congenital/developmental disorders aiming to identify possible new genomic variants;

2) Integration in the international endeavor of identifying and confirming new genomic variants for these rare disorders through active participation and inclusion of the Romanian data in the multi-center international consortia.

3) Implementation of a complex genome profiling diagnostic algorithm for patients with congenital and developmental abnormalities and use the integrated results for improving diagnostic yield, genetic counseling and clinical management.

The partnership consists of Stefan S. Nicolau IVN Bucharest, that will set-up the cells/DNA/RNA sample bank and perform PCR, MS-MLPA, sequencing analysis; Alfred Rusescu IOMC Bucharest and Grigore T. Popa UMF Iaşi that will recruit the patients, perform the phenotype/formal-genetic analysis and clinical management of the patients, and Personal Genetics Ltd. which will perform aCGH and next generation sequencing, will integrate the results of the analysis and will apply the resulting algorithm, firstly in their practice, and next will disseminate it to a clearly defined target market. The consortium represents a specialized and complementary team, capable to advancing the knowledge on clinical management, prevention, and eventually, therapy of congenital and developmental abnormalities, and to join international research effort in this direction.

Investigation of viral and host markers of non-response to anti-viral treatment in chronic hepatitis C Call name: Joint Applied Research Projects - PCCA-2011 call, Type 2
PN-II-PT-PCCA-2011-3.2-1150 2012 - 2016

Role in this project:

Coordinating institution: INSTITUTUL NATIONAL DE CERCETARE CANTACUZINO

Project partners: INSTITUTUL NATIONAL DE CERCETARE CANTACUZINO (RO); SPITALUL DE BOLI INFECTIOASE "DR.VICTOR BABES" (RO); INSTITUTUL CLINIC FUNDENI (RO); INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO); PERSONAL GENETICS S.R.L. (RO)

Affiliation: PERSONAL GENETICS S.R.L. (RO)

Project website: http://www.cantacuzino.ro/ro/?p=1713

Abstract:

The hepatitis C virus (HCV) genotype 1b is associated with higher rates of liver cirrhosis and poorer response to antiviral therapy. Sustained virological response to pegylated interferon/ ribavirin is achieved in only half of genotype 1-infected patients(prevalent in Romania). Starting with 2011, new treatments are available including specific protease inhibitors in addition to PEG-Interferon and ribavirin. Failure of IFN-based treatments to eradicate HCV infection has been shown to be related to virological (HCV genotype, variability, viral load, on-treatment viral kinetics), host genetic determinants (genetic variation near the IL28B gene) and non-genetic factors (age, sex, fibrosis, etc.). So far, no study characterizing HCV resistance pattern or genetic features among chronic HCV patients from Romania is available. The project aims to define the pre-treatment prediction of response to PEG-IFN/RBV therapy through the integrated analysis of viral factors as well as host factors. This study implies a prospective recruitment of patients with chronic hepatitis C in accordance with the Helsinki Declaration. All serological, biochemical, histo-pathological and genetic assays will be performed on samples routinely taken in regular clinical practice. The presence of the described mutations to the current or the tri-therapy in complete viral protein-coding regions and the variability impact on the resistance phenotype using both the traditional sequencing method and a next generation approach will be evaluated. Selected HCV genomic regions will serve to design primers and to develop specific PCR systems capable to detect resistance mutations. Human genetic markers (IL28B, HLA-B27, ITPA genes polymorphisms) and serum proteins (IP-10) will be tested for treatment prediction. A computer based algorithm including host and viral factors will be developed to support selection of the optimum treatment in the context of personalized medicine.

Molecular markers as predictors of treatment outcome and global prognosis in the management of differentiated thyroid carcinoma. Call name: Joint Applied Research Projects - PCCA-2011 call, Type 2
PN-II-PT-PCCA-2011-3.2-1337 2012 - 2016

Role in this project:

Coordinating institution: INSTITUTUL NATIONAL DE ENDOCRINOLOGIE "C.I.PARHON" BUCURESTI

Project partners: INSTITUTUL NATIONAL DE ENDOCRINOLOGIE "C.I.PARHON" BUCURESTI (RO); INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO); INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU'' (RO); AGILROM SCIENTIFIC SRL (RO)

Affiliation: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO)

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

Abstract:

Thyroid cancer, the most frequent endocrine malignancy, is a treatable disease if properly diagnosed. However, some cases develop aggressive disease by severe mutations or dedifferentiation, while others are diagnosed incidentally while being operated for a multinodular goiter, with microcarcinomas surrounded by non-neoplastic thyroid tissue. Risk factors, environment, family history and oncogenetic events favor or trigger this transformation. The present study will evaluate the prevalence of thyroid cancer in a prospective observational approach, involving the National Institute of Endocrinology as well as other three partners: Institute of Virology Stefan S. Nicolau, Institute of Cell Biology and Pathology Nicolae Simionescu and Agilrom Scientific SRL.

Major objective of the project: Improvement of the diagnostic and follow-up protocols for thyroid differentiated carcinoma with new markers for a better treatment outcome, prognosis and quality of life

The patients will be evaluated according to current guidelines of care. In an attempt to improve the diagnostic and treatment protocols after a detailed genomic/epigenetic approach of the cases the most significant markers will be selected. A total of 300 new cases of differentiated thyroid cancer, as well as multinodular goiter controls will be followed in a 3 years cohort, being evaluated by clinical, biochemical, pathology and advanced imaging (ultrasound and I131 gamma camera) technology, as well as routine and immunohistochemistry pathology. Genetic (genomic and tumor DNA), epigenetic and proteic markers will be evaluated on biological samples (blood and tumor tissue), and compared between the groups with different tumor pathology and expected/encountered evolution. A final practical target will be the design of a microarray chip for genetic diagnosis of thyroid cancer susceptibility. Another result will be the nucleus of thyroid cancer registry in Romania and the improvement of current diagnosis and treatment

Role of S100A4 and MAP4K4 in pancreatic ductal adenocarcinoma progression Call name: Joint Applied Research Projects - PCCA-2011 call, Type 2
PN-II-PT-PCCA-2011-3.2-1490 2012 - 2016

Role in this project:

Coordinating institution: INSTITUTUL CLINIC FUNDENI

Project partners: INSTITUTUL CLINIC FUNDENI (RO); RNTECH S.R.L. (RO); INSTITUTUL DE BIOLOGIE SI PATOLOGIE CELULARA ,,NICOLAE SIMIONESCU'' (RO); INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO); INSTITUTUL ONCOLOGIC PROF.DR.ALEXANDRU TRESTIOREANU BUCURESTI (RO)

Affiliation: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO)

Project website: http://www.icfundeni.ro/S100MAP/

Abstract:

Pancreatic cancer is the fourth leading cause of cancer death both in man and women. Annually, its incidence closely matches its mortality, highlighting the limited efficacy of existing treatment options. Most pancreatic cancers are pancreatic ductal adenocarcinomas and the 5-year survival rate for patients with localized disease after surgical resection is 20% and for those with metastatic disease, the survival rate is a dismal 2%. In the last years, investigators of the pathogenesis of this disease have turned their attention to the tumor microenvironment as a critical determinant of pancreatic tumor progression and clinical outcome. To address the question of the involvement of stromal cells in the pancreatic cancer progression, this project will have a specific interest on the interplay between stellate and pancreatic cancer cells analyzing the putative tumor markers in both cellular components.

Given the expertise of the consortium and the resources of the coordinating institute – consisting of a rich tumor biobank, an established Center for Cellular Therapies and a genomic platform – the present project will pursue two of the signaling pathways of the pancreatic cancer with the long-term goal to develop new remedies for this highly lethal disease. We will examine the role of the S100 calcium binding protein A4 (S1004) and the mitogen-activated protein 4 kinase 4 (MAP4K4) in pancreatic ductal adenocarcinoma progression. In doing so, we will consolidate the expertise and maintain the critical mass of scientists in areas of excellence and recruit strong external collaborators with significant expertise in these pathways and translational cancer research. Thus, the project is to set up a partnership in a priority research field – cancer genomics – to identify new molecular mechanisms involved in pancreatic ductal adenocarcinoma progression, which may result in rapid design and implementation of new therapeutic approaches targeting these pathways.

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