BrainMap

Mrs. Adriana Plesa

Senior researcher

Senior researcher - INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU"

Researcher

Curriculum Vitae (02/10/2019)

Expertise & keywords

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: Key expert

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: Key expert

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: Key expert

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.

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: Key expert

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: Key expert

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.

STUDY ON THE USE OF HPV E4 GENE EXPRESSION IN THE CERVICAL TRANSFORMATION ZONE AS A MARKER FOR EXCLUSION OF THE RISK OF PROGRESSION TO CANCER Call name:
PC 4.1.3. - 41-081 2007 - 2010

Role in this project: Partner team leader

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

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

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

Project website:

Abstract:

Proving the presence of papillomavirus DNA in the target tissue is not enough to discern between productive or persistent infection, and less so to prove the imminent neoplasia. The virus-host cell interplay is multilayered and thus, the risk averse patient selection just by detecting viral DNA can lead to overdiagnosis. Some of these patient’s immunity will not allow the viral replication to take place and thus, the viral clearance will appear sooner, while others will develop productive infections in a tissue that sustains viral replication. In both cases, the risk for neoplasia is negligible. Stopping the events in an early stage, either through tissue non-permissiveness (how it is believed to be the case of persistent immature metaplasia) or through the incapability of the viral variant to engage the late stage of infection can lead to the apparition of the tumor. We will investigate the presence of HPV E4 protein and the nucleic acids behind it (taking into account the anti-oncogenic effect and that E4 protein activity is a hallmark of differentiation) in HPV positive patients. We will use molecular biology and immunohistochemistry techniques on cytological samples obtained during screening, and the results will be compared with the histological examination of the immunohistochemical treated samples, with focus on immature metaplasia. From high grade lesions, we will isolate and sequence ORF E4, searching for possible structural alterations that might explain the abortive infection. The cytological and histological study will be performed using a new fixing substance (HOPE), famed to preserve proteins and nucleic acids, allowing for a better detection in both fresh samples and paraffin embedded ones.

THE EXPRESSION OF THE L1 HPV18 MAJOR CAPSID PROTEIN IN THE EUKARYOTIC SYSTEM AND ITS USE IN THE PROPHYLAXIS AND MONITORING OF CERVICAL CARCINOMA Call name:
VIASAN nr 006 2001 - 2003

Role in this project: Project coordinator

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

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

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

Project website:

Abstract:

The assessment of antibody responses against HPVs (previously hampered by the lack of viral source) was enabled by the expression of the LI major capsid viral protein type 18 (HPV 18) into L929 murine cells using the pTARGET mammalian expression vector system (MEVS). The cloning was validated by PCR with specific primers for the LI gene, as well as by enzyme restriction and in situ hybridization. The evidence for the viral cloned gene expression was acquired by RT-PCR. Presence and antigenic properties of the recombinant LI protein were shown using it as antigen in an indirect enzyme linked immunosorbent assay (ELISA) system. Significantly higher reactivity was noted when the sera samples were from persons infected with HPV 18 as compared with the non-infected individuals but a moderately different reactivity was observed when the sera from patients infected with other HPV genotypes were tested. The results showed that the murine transfected cells could be used as antigen in order to delect the presence of the specific antibodies in HPV infected persons.

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