BrainMap

Mrs. Carmen Cristina Diaconu

Dr., Senior Researcher I

Senior Researcher I - INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU"

Researcher | Manager

Web of Science ResearcherID: https://publons.com/researcher/2806379/carmen-cristina-c-diaconu/

Expertise & keywords

P2X receptors as a therapeutic opportunity Call name:
COST C21130 European Cooperation in Science and Technology 2022 - 2026

Role in this project: Partner team leader

Coordinating institution: University of Ferrara

Project partners: University of Ferrara (); INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" ()

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

Project website: https://www.cost.eu/actions/CA21130/

Abstract:

P2X receptors (P2XRs) are ATP-gated ion channels involved in intercellular communication with an established role in neurodegeneration,

infection, inflammation, cancer growth, and progression. The PRESTO Action aims at accelerating the transition of P2XRs knowledge to clinical applications.

PRESTO will be accomplishing these goals by 1) promoting a coordinated effort by leading basic and clinical science experts and Industry-based investigators

aimed at the selection of the most appropriate pathologies amenable to P2XR-targeted therapy; 2) identifying the best-suited P2XR-directed drugs to take

through the clinical pipeline; 3) establishing validated experimental protocols and tools; 4) setting criteria for the validation of P2XRs as diagnostic and prognostic

biomarkers; 5) promoting dedicated clinical trials; 6) training a new, multicultural, transdisciplinary, generation of young researchers skilled in the P2XR field;

7) disseminating in the scientific community, biomedical students, charities, local and national health authorities and the general public, the awareness

of the importance of P2XR-based research.

Wastewater-based epidemiology concept as an early warning system for SARS-CoV-2 trend and its circulating variants in a defined catchment Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2021-4131 2022 - 2024

Role in this project:

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

Project partners: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO); INSTITUTUL NATIONAL DE CERCETARE -DEZVOLTARE PENTRU ECOLOGIE INDUSTRIALA - ECOIND (RO)

Affiliation:

Project website: https://virology.ro/grant/wastewater-based-epidemiology-concept-as-an-early-warning-system-for-sars-cov-2-trend-and-its-circulating-variants-in-a-defined-catchment/

Abstract:

Covid-19 disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China in December 2019 and gave rise to a worldwide health emergency after only 2 months. Currently, more than 226 million cases have been confirmed and over 4.6 million deaths worldwide. In Romania, the numbers are raising with over 1.1 million confirmed cases and more than 35k deaths. The well-known lineages, B.1.1.7 (Alpha variant), B.1.351 (Beta variant), P.1 (Gamma variant) and B.1.617.2 (Delta variant) assigned as variants of concern (VOCs), show an increased transmissibility and higher infectivity. Lately, it has been observed that the VOCs exhibit an increased resistance towards the vaccines and therapies, especially the Delta variant. Considering the ascending number of infections with SARS-CoV-2 variants and the necessary time for the symptoms onset in infected individuals, a delay of the real active cases reported per day can be observed. Wastewater based epidemiology (WBE) proved to be a powerful tool for the early detection of SARS-CoV-2 concentrations in a certain catchment and to provide a quick snapshot about the circulating variants before they are seen in clinical cases. The scope of the project is to demonstrate that the early detection of an increasing trend in total SARS-CoV-2 concentration and assessment of its circulating variants in wastewater represent the key factor in the pandemic containment. Furthermore, the present proposal aims to demonstrate the infectivity of SARS-CoV-2 in untreated wastewater samples from Bucharest, which is of paramount importance for the public health. Noteworthy, the study aims to support the collective efforts of the EU Sewage Sentinel System by implementing a wastewater based surveillance approach in Romania as recommended by the European Commission. EU strongly encourages the member states to implement the wastewater surveillance system for SARS-CoV-2 and its variants before October 1st 2021.

Molecular Profiling of Myeloproliferative Neoplasms and Acute Myeloid Leukemia for Designing Early Diagnostic, Prognostic and Treatment Strategies Call name:
COP A1.1.4 E/P37_798/SMIS 106774 2016 - 2023

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: https://virology.ro/grant/myeloal/

Abstract:

The objective of the project is to establish a high-level nucleus of competence in studying molecular mechanisms of Myeloproliferative Neoplasms (MPNs), their transformation into Secondary Acute Myeloid Leukemia (sAML), and de novo AML with normal karyotype (dnAML), in a medical institute from Romanian Academy, under the leadership of a researcher with trail-blazing discoveries in the field, and remarkable international experience in the private research sector, as well as in academic research.

Psychosis polygenic risk score in the Romanian population and participation to the PGC international genetic study of bipolar disorder Call name: P 4 - Proiecte de Cercetare Exploratorie, 2020
PN-III-P4-ID-PCE-2020-2269 2021 - 2023

Role in this project:

Coordinating institution: SPITALUL CLINIC DE PSIHIATRIE PROF.DR.ALEXANDRU OBREGIA

Project partners: SPITALUL CLINIC DE PSIHIATRIE PROF.DR.ALEXANDRU OBREGIA (RO)

Affiliation:

Project website: https://www.bio.unibuc.ro/index.php/departamente/anatomie-fiziologie-animala-si-biofizica/47-proiecte-de-cercetare/458-prsbp-pgc

Abstract:

Bipolar disorder (BP) is a severe psychiatric disorder with chronic course that affects 2% of every population. No efficient treatment exists at present. The project continues our efforts of disentangling the genetic basis of BP in international collaboration using genomewide scanning of patients and healthy controls with the following objectives: 1) identification of new genes and replication of genes previously found associated with BP (our publications in Nature Genetics, 2019; Cell, 2018, Mol. Psychiatry, 2018, Lancet, 2016, etc); 2) the influence of BP subphenotypes on the lithium maintenance treatment response (age of onset, onset polarity, chronicity); 3) use of polygenic risk scores (PRS) SNP-sets for schizophrenia (SCZ) (2020) and BP (SNP-set 2021) derived from large scale GWAS of Psychiatric Genomics Consortium (PGC) ( where the Romanian sample is integrated) for phenotypic risk prediction in Romanian and UK patients and treatment response; 4) extention of the Romanian sample integrated in international consortia (PGC and ConLiGen). The methods include clinical investigation of the subjects with psychiatric genetic interviews (DIGS, FIGS), genomewide genotyping and use of statistical genetic methods (PLINK/ PREsci , GCTA, MAGMA, mendelian randomization, other methods if needed) for detecting new genome-phenom associations, genetic overlap between two major psychoses (BP and SCZ) and drug-able genes with potential for improving the pharmacological treatment o

Pan-European Response to the ImpactS of COVID-19 and future Pandemics and Epidemics Call name: EC - H2020
H2020-231779-101016233 2020 - 2023

Role in this project: Partner team leader

Coordinating institution: UNIVERSITA DEGLI STUDI DI PAVIA

Project partners: UNIVERSITA DEGLI STUDI DI PAVIA (IT); INSTITUT FUER HOEHERE STUDIEN - INSTITUTE FOR ADVANCED STUDIES (AT); INSTITUTUL DE VIRUSOLOGIE STEFAN S. NICOLAU (RO); FONDAZIONE IRCCS POLICLINICO SAN MATTEO (IT); INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (FR); CENTRE FOR EUROPEAN POLICY STUDIES (BE); FORUM DES PATIENTS EUROPEENS (BE); UNIVERSITEIT GENT (BE); LONDON SCHOOL OF ECONOMICS AND POLITICAL SCIENCE (UK); SOCIEDADE PORTUGUESA DE INOVACAO CONSULTADORIA EMPRESARIAL E FOMENTO DA INOVACAO SA (PT); TECHNISCHE UNIVERSITAET MUENCHEN (DE); NARODNI USTAV DUSEVNIHO ZDRAVI (CZ); GENEGIS GI SRL (IT); ASSISTANCE PUBLIQUE HOPITAUX DE PARIS (FR); FEDERATION EUROPEENNE DES ACADEMIESDE MEDECINE (BE); HANDELSHOGSKOLAN I STOCKHOLM (SE); UNIVERSITA DELLA SVIZZERA ITALIANA (CH); AGENCIA DE QUALITAT I AVALUACIO SANITARIES DE CATALUNYA (ES); JOHANN WOLFGANG GOETHE-UNIVERSITAET FRANKFURT AM MAIN (DE); EUROPEAN REGIONAL AND LOCAL HEALTH AUTHORITIES ASBL (BE); MENTAL HEALTH EUROPE - SANTE MENTALE EUROPE (BE); POLITECNICO DI MILANO (IT); UNIVERSITA DEGLI STUDI DI TRENTO (IT); KAROLINSKA INSTITUTET (SE); ISTITUTO PER L'INTERSCAMBIO SCIENTIFICO (IT); PREDUZECE ZA INFORMACIONE TEHNOLOGIJE I ELEKTRONSKO TRGOVANJE BELIT DOO (RS); AGORA SA (PL); UNIVERSIDAD POLITECNICA DE MADRID (ES); FEDERATION EUROPEENNE DES HOPITAUX ET DES SOINS DE SANTE (BE); TECHNISCHE UNIVERSITEIT DELFT (NL); ECOLE DES HAUTES ETUDES EN SANTE PUBLIQUE (FR); MODEFINANCE SRL (IT)

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

Project website:

Abstract:

Mechanisms and biomarkers of response and resistance to current targeted therapies in gastric cancer Call name: P 4 - Proiecte Complexe de Cercetare de Frontieră
PN-III-P4-ID-PCCF-2016-0158 2018 - 2022

Role in this project:

Coordinating institution: INSTITUTUL CLINIC FUNDENI

Project partners: INSTITUTUL CLINIC FUNDENI (RO); UNIVERSITATEA DE MEDICINA SI FARMACIE CRAIOVA (RO); INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO)

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

Project website: https://cemt.ro/proiect/therres/

Abstract:

Gastric cancer (GC) is a heterogeneous disease with almost one million new cases occurring annually worldwide. Recent developments provide the unprecedented opportunity to make substantial progress in GC therapy. Targeted therapies have revolutionized the therapy of GC, but the benefits remain limited to a few months of increased survival.

The challenge is now how to best stratify patients for therapy, and to identify ‘druggable’ primary and acquired resistance.

Limited studies have been performed to evaluate biomarkers for predicting response to anti-HER2, anti-MET, anti-VEGFR2 therapy in GC, and immune checkpoints that contribute to tumor resistance. Moreover, combining targeted strategy with immune checkpoint inhibition – the most exciting and active area of research currently because of durable responses seen in melanoma and lung cancer – are among the new frontiers of research in the cancer treatment and could represent a quantum leap in the therapy of GC.

The project specific objectives are:

Objective 1: To explore potential biomarkers and targets for therapy in GC subtypes defined based on contemporary disease classifications

Objective 2: To examine biomarkers of response and resistance to standard anti-HER2, anti-MET, and anti-VEGF therapy in GC

Objective 3: Characterization of the particular features of GC vascular stroma, including the study of the potential role of immune checkpoints in GC subtypes

As a key output, the project will generate decision making tools for treatment and management of GC patients in a personalized approach. The results of the present project will help improve the performance, quality and international visibility of Romanian scientific results in oncological field.

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:

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.

Regression-based characterization of mechanisms involving CEACAM-1 in melanoma – an innovative approach for optimizing the management of patients with thin melanomas Call name: P 4 - Proiecte de Cercetare Exploratorie
PN-III-P4-ID-PCE-2016-0641 2017 - 2019

Role in this project:

Coordinating institution: UNIVERSITATEA DE MEDICINA SI FARMACIE "CAROL DAVILA"

Project partners: UNIVERSITATEA DE MEDICINA SI FARMACIE "CAROL DAVILA" (RO)

Affiliation: UNIVERSITATEA DE MEDICINA SI FARMACIE "CAROL DAVILA" (RO)

Project website: https://umfcd.ro/en/research-and-development/national-projects/ceacammel/

Abstract:

Melanoma has overall rising incidence with increased incidence in young patients and high mortality rate in metastatic stage. The extreme variation in natural and therapeutic evolution and unexplained mortality of thin melanomas classified in the same TMN stage highlight the need of new biomarkers and ultrastaging.

The project brings in focus carcinoembyonic antigen cell adhesion molecule 1 (CEACAM1), key molecule involved in tumorigenesis, mainly in epithelial-mesenchymal transition (being responsible for gaining invasiveness and metastatic capacity) and immune escape (by inhibiting effector functions of tumor infiltrating lymphocytes). To decipher CEACAM1 role in modulating aggressive thin melanoma behavior, we chose to study it for the first time in regressing melanoma (RM) vs non-regressing melanoma (nRM), regression phenomenon being used as a valuable model for understanding antitumor immunity.

We will assess CEACAM1 isoforms expression using IHC, RT-PCR and WB in thin RM&nRM melanomas and ELISA for serologic tests. Retrospective studies [tissue microarrays from archived tumor tissue of 90 cases of RM, 90 nRM, 30 halo nevi and 30 common nevi (as benign control)] and prospective studies (plasma, frozen and paraffin-embedded tumor tissue from 30 cases of thin RM, 30 thin nRM, 10 halo nevi and 30 common nevi) will be performed. We assembled a multidisciplinary team including senior and junior researchers under the supervision of a highly experienced researcher with extensive expertise in multiple enzymatic and fluorescent IHC and complex morphometric analysis. We will analyze the correlation between CEACAM1 deregulation and prognosis, intratumor inflammatory infiltrate and consecrated progression-related tissue markers.

This approach will clarify the mechanisms through which CEACAM1 isoforms are involved in progression and regression of thin melanomas, as a starting point for new risk stratification of early melanomas and a better management of these patients.

Rationally designed therapeutic vaccine against HIV-1 based on a novel formulation of nanoparticle-protected mRNA Call name: P 3 - SP 3.2 - Proiecte ERA.NET
HIVERA-HIV-NANOVA 2016 - 2018

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/ro/hiv-nanova-home

Abstract:

Recent data demonstrate the feasibility of dendritic cell based therapeutic vaccines to control HIV-1 infection. Nevertheless, their patient specific nature, the specialized infrastructure, the high level of expertise required for preparation and the high demands for storage and transportation preclude widespread application and commercialization. Therefore novel vaccine candidates that retain the power of a DC-based vaccine but at the same time overcome its limitations need to be developed. mRNA-based vaccines offer significant promise in this respect. It was shown that mRNA is selectively taken up by dendritic cells upon injection in the lymph node and induces strong antigen specific immune responses. Therefore, an interesting vaccine candidate could be an mRNA-based vaccine able to deliver both a rationally designed HIV antigen sequence and on the other hand potent activation signals. An important drawback of this approach is the fact that intranodal immunization is not easily applicable in clinical settings. Therefore, more standardized routes of administration need to be explored. Given the inherent sensitivity of RNA to ambient RNases, these approaches will require protection of mRNA. In this project we will evaluate the feasibility of delivering an mRNA based therapeutic vaccine with biodegradable nanoparticles loaded with RNA entrapped at their surface through a lysine-derived poly-lactic acid based polymer.

Composite hydrogels based on inorganic nanoparticles and collagen with prolonged antimicrobial activity for the prevention of wound infections Call name: P 2 - SP 2.1 - Proiect de transfer la operatorul economic
PN-III-P2-2.1-PTE-2016-0177 2016 - 2018

Role in this project: Key expert

Coordinating institution: SANIMED INTERNATIONAL IMPEX S.R.L.

Project partners: SANIMED INTERNATIONAL IMPEX S.R.L. (RO); UNIVERSITATEA BUCURESTI (RO); UNIVERSITATEA POLITEHNICA DIN BUCURESTI (RO); INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO)

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

Project website: http://nanocolagel.sanimed.ro/

Abstract:

Chronic wounds represent a good niche for biofilm development because the impaired immune response promotes infection susceptibility whilst necrotic tissue and debris favor bacterial attachment. Collagen hydrogels represent one of the most efficient treatments in case of both chronic and acute wounds due to their ability to maintain optimal humidity and aeration parameters. Currently, at a national level there is no production of collagen hydrogels aimed for the treatment of chronic wounds, hence these types of products are being imported. In this context, the present project proposal aims to design and obtain new types of multifunctional collagen hydrogels harboring antimicrobial properties in order to favor the healing process of chronic wounds. As a novelty element in comparison to products currently available on the international market, we will design and produce collagen hydrogels containing nanoparticles. Thus, Sanimed International Impex S.R.L will develop a simple and rapid technology to obtain hydrogels functionalized with metalic and oxidic nanoparticles (collagen hydrogels with Ag nanoparticles, collagen hydrogels with ZnO hydrogels and collagen hydrogels with SiO2@ZnO nanoparticles). The novel hydrogels will be tested for their antimicrobial and antibiofilm properties using in vitro and in vivo methods and also for the host response after hydrogel treatment on wounded cells and in vivo lesion murine models, for achieving market preparation.

Knowledge Transfer on investigation of the anti-infective and antitumoral activity of novel cosmetic and pharmaceutical formulations based on natural extracts Call name: P 2 - SP 2.1 - Transfer de cunoaștere la agentul economic „Bridge Grant”
PN-III-P2-2.1-BG-2016-0369 2016 - 2018

Role in this project: Key expert

Coordinating institution: UNIVERSITATEA BUCURESTI

Project partners: UNIVERSITATEA BUCURESTI (RO); INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO); HOFIGAL EXPORT IMPORT SA (RO)

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

Project website: https://icubresearch.wordpress.com/2018/10/19/bg-369/

Abstract:

The present project proposal aims the development of an innovative methodology for testing the antimicrobial, antiviral, anti-tumor and immunomodulatory activity, and to elucidate the mechanisms of action at the cellular and molecular level of natural bee and plant extracts with the purpose of introducing them în new cosmetic and pharmaceutical formulations, for expanding the marketed products range of the economic agent participating în the project - Hofigal S.A.

The addressed strategy is based on abundant scientific literature and original experimental results of all involved partners regarding the characterization and marketing of natural products / compounds with therapeutic or prophylactic value.

The proposed project falls into a major research direction aimed at the discovery of complementary therapeutic solutions based on natural compounds, for the treatment of different pathologies (i.e., infectious diseases and cancer), which are currently found în the top of causes of global morbidity and mortality.

The therapeutic alternatives that will be investigated în this project are based on natural compounds of vegetal and bee origin, with high therapeutic and preventive potential, due to the following properties: complex composition that allows simultaneous action on multiple biological targets; decreased risk for selecting resistance, both în case of infectious agents, such as viral, bacterial and fungal, and în the case of tumor cells; immunomodulatory effect; high biocompatibility; minimal or no side effects.

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.

GENOMEWIDE STUDY OF BIPOLAR I DISORDER AND GUIDE FOR ASSESSING THE GENETIC RISK FOR BIPOLAR I DISORDER IN THE ROMANIAN POPULATION Call name: Joint Applied Research Projects - PCCA-2011 call, Type 2
PN-II-PT-PCCA-2011-3.2-1628 2012 - 2016

Role in this project:

Coordinating institution: SPITALUL CLINIC DE PSIHIATRIE PROF.DR.ALEXANDRU OBREGIA

Project partners: SPITALUL CLINIC DE PSIHIATRIE PROF.DR.ALEXANDRU OBREGIA (RO); INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO); UNIVERSITATEA BUCURESTI (RO); PERSONAL GENETICS S.R.L. (RO)

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

Project website: http://www.bio.unibuc.ro/index.php?option=com_content&view=article&id=212%3

Abstract:

Medicine develops into three directions: prevention, prediction and personalization. Bipolar I disorder (BPI) is a chronic major psychiatric disease with a polygenic basis not yet elucidated. The objectives of the project are: 1) fine mapping of two haplotypes in NCAN and MAD1L1 genes found associated with BPI in a previous genomewide association study (GWAS) (Cichon et al, Am J Hum Genet, 2011) in which the project coordinator was involved; 2) a GWAS of the response to lithium therapy aiming at detecting the genotypes linked to positive response; 3) estimating morbid risks (MR) for relatives of BPI patients valid for the Romanian population; 4) determining the structure of Mad1 and Mad2 molecules and their neurobiological consequences with potential impact on drug development; 5) development of a guide for genetic counseling containing genotypes associated with BPI in the Romanian population, MR for relatives of patients, phenotypic variables that increase MR and genotypes predicting the positive response to lithium. The study will be conducted in an international consortium including Romanian partners. A Romanian sample of about 550-570 patients and 550-570 controls will be integrated in an international sample of several thousands of patients and controls that will be genotyped with high-throughput methods (Illumina, Sequenom) by Romanian researchers at the German partner and with next generation sequencing technology atone of the Romanian partners. Probands and their available first degree relatives will be investigated with DIGS and FIGS interviews and will provide psychiatric family history necessary for estimating MR. The response to lithium therapy in patients treated at least one year will be rated with the Alda scale. Our sample of lithium-patients will be integrated in the international lithium sample for genotyping. The biometric and molecular results of the study will be implemented in personalized medicine by a private health care company and disseminated among specialists.

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

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.

FILE DESCRIPTION	DOCUMENT
List of research grants as project coordinator
List of research grants as partner team leader
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