BrainMap

Anca Botezatu

- INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU"

Researcher

Web of Science ResearcherID: not public

Expertise & keywords

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.

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