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Role of IL-6/NF-κB/HIF-1 axis in adipose tissue mesenchymal stromal cells-mediated breast cancer cells stemness

Project leader : Dr Trivanović Drenka

Project collaborators:

Dr Aleksandra Jauković, dr Ivana Okić-Đorđević, dr Tamara Kukolj

Project number: SK-SRB-2016-0031

Duration of the project: 2017- 2018

Leading Institution:

Description of the project:

Mesenchymal stromal/ stem cells (MSC) from adipose tissue play an important role in the tumor microenvironment of breast cancer, but the molecular basis of their participation in the regulation of tumor development and progression is insufficiently studied. Persistent inflammation and hypoxia in tumor tissue contribute to the development of cancer stem cells and tumor progression, where transcription factors NF-κB and HIF-1 cooperate to govern the cancer progression.
In order to define potential new targets for the development of antitumor therapeutic strategies, this project aimed to define molecular mechanisms underlying the influence of adipose tissue MSC on stemness properties of breast tumor cells with a special focus on the participation of IL-6/NF-κB/HIF-1 signaling pathway. For these purposes, the effects of MSC adipose tissue or their produced factors on breast tumor cell line MDA-MB-231 were analyzed in terms of mammospheres formation, expression of pluripotency markers, cell cycle/silencing, and modification of NF-κB and/or HIF-1 activation.

Тип пројекта:

International Projects

Genome Editing to Treat Humans Diseases

Project leader: Karim Benabdellah

Project collaborators:

Drenka Trivanović (MC member), Aleksandra Jauković, Sanja Vignjević-Petrinović, Ivana Drvenica

Project number: CA21113

Duration of the project: September 2021. – September 2025.

Leading Institution: Fundación Pública Andaluza, Progreso y Salud, Granada, Španija

Description of the project:

Recent advances on genome editing technologies have opened the possibility of treating diseases through precise modifications of patients’ genomes. However, the translation of the genome editing technologies to address public health needs, require a strong collaboration between basic and clinical research, regulatory bodies and the different stake holders involved for each application. There are several networks to improve or analyse genome editing technologies for different applications, however, no one cover all the actors involved in gene therapy translation. The principal aim of the GenE-HumDi Action is to bring together pharmaceutical companies, academic institution, science and regulatory agencies, biotechnology firms, patient advocacy association and information technology, in order to tackle knowledge fragmentation with the aim to accelerate the translation of GE technologies to the treatment of human diseases.

Тип пројекта:

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New therapeutic strategies for reconstruction of bone defects with optimized RIA-derived autologous grafts and bone substitute materials

Project leader: dr Herrmann Marietta

Project collaborators:

Aleksandra Jauković, Ph.D. (coordinator of the work package WP3 and proof-of-concept with 3D Republika), Kukolj Tamara, Ph.D., Hristina Obradović, Ph.D., Milena Živanović, PhD student

Project number: 01DS21004

Duration of the project: July 2021 – June 2024

Leading Institution: University Hospital Würzburg

Description of the project:

Large bone defects present a common clinical problem where autologous bone grafting is the current gold standard. Autologous bone grafts harvested by the Reamer-Irrigator-Aspirator® (RIA) technique are considered advantageous in terms of larger quantities of graft material and yielding two fractions – a solid graft usually used for the transplantation and a liquid fraction often referred to as a waste material. This highly translational project aims to address the regenerative potential of RIA liquid fraction through in vitro studies of its secretory and cellular content as well as by testing pre-conditioning strategies to improve RIA grafts regenerative potential. Also, the project will provide evidence for the new application possibility of bone substitute material PerOssal® (Osartis GmbH) in combination with RIA-graft material. In vitro experiments will be translated into preclinical and clinical trials in Serbia to optimize currently available therapies. In parallel, proof-of-concept experiments with 3D printing materials will be accomplished with the industrial partner from Serbia 3D Republika d.o.o.

Тип пројекта:

International Projects

The European Network for Stem cell Core Facilities

Project leader : Laura Batlle Morera

Project collaborators:

Aleksandra Jauković (MC member), Ivana Okić Đorđević, Slavko Mojsilović, Tamara Kukolj

Project number: CA20140

Duration of the project: October 2021 – October 2025

Leading Institution: Center for Genomic Regulation, Barselona, Španija

Description of the project:

CorEuStem is formed upon recognizing the need to connect core facilities in European research centers and universities that provide services in such fields as disease modelling, embryology, and novel regenerative therapeutic approaches, to keep track of all advancements in cutting-edge technologies. This network is composed of experts in stem cell, differentiation, organoids, and gene editing technologies with the aim of joining forces and establishing the first European network for harmonizing procedures and protocols, to organise joint training schools for implementing new cutting-edge technologies emerging in the field and to become a reference point in stem cells, differentiation, organoids and gene editing in Europe and beyond. The IMR team, having extensive experience in adult stem cell research, has embraced the opportunity to become a part of this network of experts, hoping of both gaining insights in emerging technologies and providing a competent input to the consortium.

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In vitro total cell guidance and fitness

Project leader: Tiziana Brevini

Project collaborators:

Aleksandra Jauković (MC member), Drenka Trivanović (MC substitute), Tamara Kukolj, Hristina Obradović, Ivana Okić Đorđević

Project number: CA16119

Duration of the project: March 2017. – September 2021.

Leading Institution: Universita degli studi di Milano, Milano, Italija

Description of the project:

The aim of this COST Action is to refine the present understanding of in vivo micro/macro-environment in order to reproduce in vitro the physiological system in the best possible way: surface topography, substrate stiffness, mechanical stimulation, chemical cues and localized density will be analyzed. This will allow to develop reliable “3D total guidance” in vitro models reducing the number of animals used and allowing a safe translation of the present basic knowledge in cell repair and regeneration from the laboratory bench to the clinical application, with a positive impact on every day’s life patients and general Health costs. Researches in this field are being performed by different groups in the EU, but efforts need to be coordinated in order to avoid duplication, set targets and guidance for future research and to standardize protocols through a large interdisciplinary collaborative EU network. These goals can only be achieved under a COST program.

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Converting molecular profiles of myeloid cells into biomarkers for inflammation and cancer

Project leader : Sven Brandau

Project collaborators:

Juan F. Santibañez (MC Member), Slavko Mojsilović, Milica Vukotić

Project number: CA20117

Leading Institution: октобар 2021. – октобар 2025

Водећа институција: University Hospital Essen, Esen, Nemačka

Description of the project:

Myeloid immune cells are important mediators in the pathology of many diseases, especially in diseases associated with chronic inflammation (DACI). Recent advancements in molecular profiling technologies have led to the generation of large data sets, many of those not fully explored yet, but accessible to the entire scientific community via public data repositories. It is the aim of this COST Action to repurpose those data sets, retrieve and curate myeloid cell-specific information, and apply this information to develop novel biomarkers for DACI. To this end, Mye-InfoBank utilise COST networking tools to enable the interaction of molecular biologists, bioinformaticians, immunobiologists, biobank coordinators and clinicians. The concerted activity of these experts on myeloid cell biology (either basic or clinical research), bioinformatics, and bio-banking, will transform complex molecular information into standardised and applicable biomarkers, which have the potential to improve clinical decision making in a number of socio-economically important diseases.

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European Network of Investigators Triggering Exploratory Research on Myeloid Regulatory Cells

Project leader: Sven Brandau

Project collaborators:

Juan F. Santibañez (MC Member), Vladan Čokić (MC Substitute), Slavko Mojsilović, Jelena Krstić, Sunčica Bjelica

Project number: BM1404

Duration of the project: November 2014 – November 2018

Leading Institution: University Hospital Essen, Esen, Nemačka

Description of the project:

This Action formed a network of researchers and clinicians with the aim to establish a gold standard of common protocols and harmonize guidelines for the analysis and clinical monitoring of myeloid regulatory cells (MRCs). There is also a deficit in the translation of findings from animal models to humans, and Mye-EUNITER built an analytical mouse-monkey-man correlation line. Standardized and validated tools for MRC analysis aid the development of cellular biomarkers of disease and guide the design of novel therapies to manipulate the functions of MRCs. Members of the Action from IMR actively engaged in the activities of working groups through attending meetings, workshops, short-term scientific missions, and writing papers.

Тип пројекта:

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Regenerative and modulatory potential of adult stem cells

Project leader: Diana Bugarski

Project collaborators:

Aleksandra Jauković, Slavko Mojsilović, Drenka Trivanović, Ivana Okić Đorđević, Tamara Kukolj, Hristina Obradović, Jelena Krstić, Juan F. Santibañez, Sanja Vignjević Petrinović, Sanja Momčilović, Irina Maslovarić

Project number: OI 175062

Duration of the project: January 2011 – December 2020

Leading Institution: Институт за медицинска истраживања, Универзитет у Београду

Description of the project:

This project aimed to investigate the cellular and molecular aspects of the biology and function of multipotent adult stem cells, specifically hematopoietic stem cells and mesenchymal stromal cells. At the beginning of the project period, mesenchymal stromal cells were isolated and characterized (phenotypically and functionally) from various tissues of human and animal origin, including bone marrow, adipose tissue, umbilical cord, dental pulp, and periodontal ligament. In the following phase, the role and mode of action of various factors, primarily the inflammatory microenvironment, on the functional properties of adult stem cells were investigated, as well as the interaction of mesenchymal stromal cells with hematopoietic, immune, and tumor cells, with a particular focus on their role in immunoregulation and tumorigenesis. This project resulted in over 60 publications and presentations at scientific conferences (including 35 in JCI-indexed journals).

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National Projects

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