BrainMap

Mrs. Marinela Bostan

Senior researcher I

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

Researcher

Web of Science ResearcherID: AAC-5658-2019

Curriculum Vitae (05/11/2024)

Expertise & keywords

Proteomic screening of bronchoscopic biopsies-on-chip for improved prediction of anti-PD-1 responses in real-time Call name: P 3 - SP 3.2 - Proiecte ERA.NET
ERANET-PERMED-BronchoBOC 2020 - 2023

Role in this project:

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

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

Affiliation:

Project website: https://virology.ro/grant/bronchoboc/

Abstract:

Anti-PD-1 monotherapy first-line is indicated for patients with advanced non-small-cell lung cancer (NSCLC), accompanied by non-targetable driver mutations and >50% PDL1 expression. Still, more than half of patients do not respond or become resistant after an initial response. Identifying patients who will benefit from anti-PD-1 monotherapy or need more aggressive combinatorial therapy is an unmet need. Three-dimensional primary microfluidic cultures may capture the dynamic tumor-immune interplay and guide treatment through reverse translation. CCL19 and CXCL13 released in melanoma-derived microfluidic cultures correlate with clinical responses. Whether and how similar approaches can be applied to lung cancer, is to be defined. We aim to interrogate the applicability of an innovative 3D microfluidic device, i.e. organ-on-chip, in predicting real-time response to PD1-blockade in NSCLC patients.

Bronchoscopic tumor biopsies are minimally invasive, routinely obtained from advanced NSCLC patients and are thus ideal for personalized drug screening. We will develop and validate the first bronchoscopic biopsies-on-chip (bronchoBOC). We will conduct a prospective multicentric exploratory co-clinical trial by studying in parallel clinical responses (complete/partial remission, progression, overall survival, and progression-free survival) to a-PD1 monotherapy in treatment-naive advanced NSCLC patients (n≈48) matched to their bronchoBOCs. We will profile proteome responses to a-PD1 using mass spectrometry (LC-MS/MS), FACS, cytometric bead arrays, together with immunofluorescence and imaging. Artificial intelligence/machine learning approaches will be allied to bronchoBOC profiles and clinical data, to identify the best predictive biomarker patterns and validate them in a multi-feature model. The predictive model will be hosted in an easy to use interface to predict response to a-PD1.

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.

Multi-disciplinary platform for regional institutional capacity enhancing in dermatooncology and dermato-pathology domains Call name: P 1 - SP 1.2 - Proiecte complexe realizate in consorții CDI
PN-III-P1-1.2-PCCDI-2017-0341 2018 - 2021

Role in this project: Partner team leader

Coordinating institution: SPITALUL CLINIC "COLENTINA" BUCURESTI

Project partners: SPITALUL CLINIC "COLENTINA" BUCURESTI (RO); INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE IN DOMENIUL PATOLOGIEI SI STIINTELOR BIOMEDICALE "VICTOR BABES" (RO); INSTITUTUL DE BIOCHIMIE (RO); UNIVERSITATEA BUCURESTI (RO); UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" (RO); UNIVERSITATEA DE MEDICINA SI FARMACIE "CAROL DAVILA" (RO)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE IN DOMENIUL PATOLOGIEI SI STIINTELOR BIOMEDICALE "VICTOR BABES" (RO)

Project website: http://cdpcolentina.ro/buton11pathderm.html

Abstract:

Dermato-oncology and dermato-pathology address the most frequent pathology, but the medical training is scarce, hence the new diagnosis and treatment approaches in skin cancers are frugaly tought in residency and in post-universitary training. Thus, the medical act is hindered by the “in-house” training of the clinicians that can lead to low quality medical serivces for the patient. The project re-unites 6 prestigious institutes that have prior collaborated (Bucharest, Cluj): an university hospital, a national institute, a Romanian Academy national institute and 3 universities (two medical ones) that propose for the first time on national level a research and training platform for dermato-oncology and dermato-pathology developing 4 multi-disciplinary projects. Project 1 developps an improved diagnostic and prognostic markers for the most frequent skin cancers- squamous cell and basal cell carcinomas. Project 2 identify the markers for improved prognosis and therapy monitoring in cutaneous melanoma. Project 3 develops new methologies for therapy testing in dermato-oncology and dermato-pathology. Project 4 completes the training slope of young researchers and medical doctors to increase the medical services quality (decrease social costs of the dermato-oncology pathology) and to increase the research results in the biomedical domain. We estimate a significant impact of the results on the institutional capacity consolidation regarding human resources (13 new research positions, several training stages, several work visits) and infrastructure (upgrading of the existent infrastructure); 3 patents, 3 new sets of biomarkers for diagnostic/prognostic/monitoring for the increase of the health care system, RD services, and international visibility improvement.

Multi-disciplinary platform for regional institutional capacity enhancing in dermatooncology and dermato-pathology domains Call name:
PN-III-P1-1.2-PCCDI-2017-0341 2018 - 2020

Role in this project: Partner team leader

Coordinating institution: SPITALUL CLINIC "COLENTINA" BUCURESTI

Project partners: SPITALUL CLINIC "COLENTINA" BUCURESTI (); INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE IN DOMENIUL PATOLOGIEI SI STIINTELOR BIOMEDICALE "VICTOR BABES" (); UNIVERSITATEA BUCURESTI (); INSTITUTUL DE BIOCHIMIE (); UNIVERSITATEA DE MEDICINA SI FARMACIE "CAROL DAVILA" (); UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" ()

Affiliation:

Project website:

Abstract:

Dermato-oncology and dermato-pathology address the most frequent

pathology, but the medical training is scarce, hence the new diagnosis

and treatment approaches in skin cancers are frugaly tought in

residency and in post-universitary training. Thus, the medical act is

hindered by the “in-house” training of the clinicians that can lead to low

quality medical serivces for the patient. The project re-unites 6

prestigious institutes that have prior collaborated (Bucharest, Cluj): an

university hospital, a national institute, a Romanian Academy national

institute and 3 universities (two medical ones) that propose for the first

time on national level a research and training platform for

dermato-oncology and dermato-pathology developing 4

multi-disciplinary projects. Project 1 developps an improved diagnostic

and prognostic markers for the most frequent skin cancers- squamous

cell and basal cell carcinomas. Project 2 identify the markers for

improved prognosis and therapy monitoring in cutaneous melanoma.

Project 3 develops new methologies for therapy testing in

dermato-oncology and dermato-pathology. Project 4 completes the

training slope of young researchers and medical doctors to increase the

medical services quality (decrease social costs of the dermato-oncology

pathology) and to increase the research results in the biomedical

domain. We estimate a significant impact of the results on the

institutional capacity consolidation regarding human resources (13 new

research positions, several training stages, several work visits) and

infrastructure (upgrading of the existent infrastructure); 3 patents, 3 new

sets of biomarkers for diagnostic/prognostic/monitoring for the

increase of the health care system, RD services, and international

visibility improvement.

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

Design and development of transport and delivery systems for new ruthenium compunds with antitumor activity Call name: Joint Applied Research Projects - PCCA-2011 call, Type 2
PN-II-PT-PCCA-2011-3.2-1454 2012 - 2016

Role in this project:

Coordinating institution: UNIV.DE MEDICINA SI FARMACIE - CAROL DAVILA

Project partners: UNIV.DE MEDICINA SI FARMACIE - CAROL DAVILA (RO); INSTITUTUL ONCOLOGIC PROF.DR.ALEXANDRU TRESTIOREANU BUCURESTI (RO); UNIVERSITATEA BUCURESTI (RO); INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO); PHARMA SERV INTERNATIONAL SRL (RO)

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

Project website: http://cercetare-umf.ro/uploads_ro/592/Pagina_web_136_2012-actualizata_2016.pdf

Abstract:

The proposed cooperative study is a complex interdisciplinary approach aimed at developing pharmaceutical product models with significant antitumor action and minimal side effects. During the project, three pharmaceutical systems that include some ruthenium complexes will be studied regarding solubility, capacity to transport and deliver the active substance at the final site of action, the antitumor activity and the side effects. The final scope of the project is to select the system (or systems) who best meet the requirements regarding bioavailability and pharmaco-toxicological properties for a possible inclusion in the clinical trials of the studied ruthenium complexes.

The proposed project has least three main goals. First, we want to develop pharmaceutical systems for improve the solubility of some ruthenium compounds in order to achieve a better pharmacokinetic profile for these compounds. Second, we intend to evaluate the antitumor activity of the developed systems using various cell lines from solid tumors and in vivo, comparing to cisplatin as reference substance. Third, we intend to evaluate the general toxicity of the developed systems, comparing to cisplatin. Additionally, we want to explore the possibility of development of these products as oral drugs and to establish what kind of cancer can be treated with these agents.

Use of genetic markers for establishing targeted therapies for laryngeal and oropharyngeal human cancer Call name:
PNCDI II Grant no. 41-084/2007 2007 - 2011

Role in this project: Partner team leader

Coordinating institution: UNIVERSITATEA BUCURESTI

Project partners: UNIVERSITATEA BUCURESTI ()

Affiliation: UNIVERSITATEA BUCURESTI ()

Project website:

Abstract:

Study of the dynamics of expression of some genes involved in cell cycle control and apoptosis in the evolution of laryngeal and oropharyngeal cancer in humans Call name:
CEEX Viasan 3255 2006 - 2008

Role in this project: Partner team leader

Coordinating institution: UNIVERSITATEA BUCURESTI

Project partners: UNIVERSITATEA BUCURESTI (RO)

Affiliation: UNIVERSITATEA BUCURESTI (RO)

Project website:

Abstract:

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