Active Projects

NEuromorphic Reconfigurable Integrated photonic Circuits as artificial image processor

Website: https://neoterich2020.eu

Starting date 4 01/01/2020

Duration in months 5 36

Call (part) identifier 6 H2020-ICT-2019-2

Topic ICT-06-2019 Unconventional Nanoelectronics

Summary:
NEoteRIC’s primary objective is the generation of holistic photonic machine learning paradigms that will address demanding imaging applications in an unconventional approach providing paramount frame rate increase, classification performance enhancement and orders of magnitude lower power consumption compared to the state-of-the-art machine learning approaches. NEoteRIC’s implementation stratagem incorporates multiple innovations spanning from the photonic “transistor” level and extending up to the system architectural level, thus paving new, unconventional routes to neuromorphic performance enhancement. The technological cornerstone of NEoteRIC relies on the development and upscaling of a high-speed reconfigurable photonic FPGA-like circuit that will incorporate highly-dense and fully reconfigurable key silicon photonic components (ring resonators, MZIs, etc.). High-speed reconfigurability will unlock the ability to restructure the photonic components and rewire inter-component connections. Through NEoteRIC the integrated photonic FPGAs will be strengthened by the incorporation of novel marginal-power consuming non-volatile high-speed phase shifters that will push the boundaries of energy consumption. NEoteRIC’s “unconventional” chips will be utilized as a proliferating neuromorphic computational platform that will merge the merits of photonic and electronic technology and will allow the alloptical implementation of powerful non-von Neumann architectures such as Reservoir Computing, Recurrent Neural Networks, Deep Neural Networks and Convolutional Neural Networks simultaneously by the same photonic chip. The in-project excellence will be tested through demanding high impact application such as high frame-rate image analysis and in particular single-pixel time-stretch modalities thus pushing the boundaries of state-of-the-art; exhibiting simultaneous high spatial resolution and Gframe/sec processing rate.


Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

Stauroula Ntoufa
Email: sntoufa@certh.gr
Tel: +30 2310 498 472

Neoantigen and tumor-specific T cell discovery in chronilymphocytic leukemia

Summary: Recent next-generation sequencing (NGS) studies by our group documented the clonal architecture of the T cell repertoire in chronic lymphocytic leukemia (CLL), with T cell clones which persist and expand over time in treatment-naive CLL, appear disease-specific and may be shared among different patients, especially those belonging to stereotyped subsets. This indicates selection by restricted antigens that could actually be acting in a CLL subset-specific context. Furthermore, we have shown that B cell receptor (BcR) signaling inhibitors retain T cell clones that may have developed in response to tumor antigens. Ιmportantly, these clones expand and may become activated, possibly contributing in the clinical response, at least in certain cases.
On these grounds, NeoCLL was launched with the aim to formally identify and fully characterize both immunogenic neoepitopes and the CD8 T cells that recognize them. We will take advantage of a novel, high-throughput method for detecting antigen-specific T cells using DNA-barcoded peptide-MHC-I multimers. Our study will focus on neoepitopes within the clonotypic BcR IG that may be conserved amongst CLL patients. The ultimate goal is to explore the possibility for a stratified treatment by means of engineered T cells or by peptide vaccines targeting such conserved epitopes.
Funding: European Hematology Association

Contact
Anna Vardi, Hematologist, Postdoctoral Researcher
E-mail: anna_vardi@yahoo.com
Τηλ.: +302311257525

Type II Diabetes Mellitus Self-Management Platform for all.

Website: https://proempower-pcp.eu/pcp-contractors/dm4all.html
Project at CORDIS: https://cordis.europa.eu/project/rcn/205948_en.html
Funding Body: ProEmpower H2020 PCP project through (https://proempower-pcp.eu/)

Summary: DM4all is developing an integrated mHealth self-management system based on software and hardware (commercial devices) solutions aiming to support type II diabetes mellitus patients. The system focuses on the unobtrusive monitoring of the patient’s health by assessing their physiological parameters and environmental variables, and on assessing the adherence to their treatment plan and the indicated lifestyle choices. Overall, DM4all will provide a personalised guidance platform through transmitting measurements to a prediction engine which will give appropriate feedback to the patients. Patients will be able to receive optimal disease management strategies (through personalised modeling), while estimated disease progression and evolution will be monitored continuously.
Clinicians and practitioners will be also equipped with novel tools to communicate with their patients and offer them the optimal, personalised care.

Contact
Vassilis Koutkias
E-mail: vkoutkias@certh.gr
Tel: +302311257615

Smart Platform for Self-management and Support of Patients with Chronic Respiratory Diseases

Website: Available soon

Funding Body: EPAnEK 2014-2020 Operational Programme co-financed by Greece and the European Union

Grant Agreement No: T1ΕΔΚ-03832

Duration: July 2018 – July 2021

Summary: The project “Take-A-Breath” focuses on the design, research and development of an innovative system of personalized monitoring services for respiratory diseases through the combination of clinical research and new bio-indicators with innovative ICT technologies, such as gamification techniques. Specifically, it enables the guidance of patients to manage their own health, by providing user-friendly tools and applications to increase awareness of the clinical situation and the effectiveness of their health care and compliance to treatment. In particular, the work focuses on clinical research into new biomarkers associated with respiratory diseases, addressing a wide range of parameters of behavioral, environmental and psycho-emotional state of the person. In addition, it adopts and develops an ambitious and innovative approach to monitor the use of inhaled respiratory drugs, combined with techniques to learn how to use it properly, through a holistic approach to self-management, medical assistance and self-improvement. On this basis, a bio-surveillance network with capacity to adapt to any inhaler will be developed using non-intrusive sensors, along with an ICT system which is capable of: (a) to collect a multitude of data relating to the above during everyday activities of the user; (b) to educate patients on the correct use of inhalation devices, using innovative signal processing and computer vision techniques, with gamification techniques and mechanisms, as well as using virtual characters and interactive narrations, and (c) to provide guidance to the patient when it is required in conjunction with a decision support system and appropriate interventions (receiving medical assistance, self-management of asthma attacks etc.).

Contact
Vassilis Koutkias
E-mail: vkoutkias@certh.gr
Tel: +302311257615

Active PharmacoVigilance in the Clinical environment

Website: Available soon

Funding Body: EPAnEK 2014-2020 Operational Programme co-financed by Greece and the European Union

Grant Agreement No: T1ΕΔΚ-03789

Duration: Sep. 2018 – Sept. 2021

Role of CERTH-INEB: Project and Scientific Coordinator

Summary: PVClinical proposes the design and implementation of a novel Information Technology (IT) platform, aiming to facilitate the identification, investigation and management of candidate Adverse Drug Reaction (ADR) signals in the clinical context. An ADR “signal” is defined as a possible causal relationship between a drug and an adverse reaction or medical condition. The PVClinical platform will exploit a number of different information sources that have been relatively neglected in traditional pharmacovigilance practices. The proposed design focuses on the unified and holistic integration of these heterogeneous data sources (international scientific literature, social media, Electronic Health Records and ADR Spontaneous Report Systems). The implementation emphasizes on the capabilities of integrating the proposed platform in existing clinical information systems via an unobtrusive manner, therefore reinforcing drug safety in everyday clinical practice.

Contact
Vassilis Koutkias
E-mail: vkoutkias@certh.gr
Tel: +302311257615

Fostering Palliative Care of Adults and Children with Cancer through Advanced Patient Reported Outcome Systems.

Website: Available soon
Project at CORDIS: Available soon

Funding Body: EUROPEAN COMMISSION, HORIZON 2020, H2020-SC1-BHC-2018-2020

Grant Agreement No: 825872

Duration: Jan. 2019 – June 2022

Role of CERTH-INEB:
• Project and Scientific Coordinator
• WP2 (“Intervention Design”) and WP8 (“Project Management”) Leader

Summary: MyPal aims to foster early palliative care for cancer patients by leveraging patient reported outcome (PRO) systems through their adaptation to the personal needs of the cancer patient and his/her caregiver(s). Through this intervention, MyPal aspires to empower cancer patients (and their family members) in capturing more accurately their conditions, communicate them with a seamless and effective way to their healthcare providers and, ultimately, foster the time for action through the rapid identification of important deviations in the patient’s state and QoL. Providing this information in a timely and comprehensive manner throughout the disease course will reinforce the potential for applying a patient-centred and integrated palliative care approach for cancer with the participation of all relevant healthcare providers (i.e. oncologists, specialized physicians, psychologists, nurses), which is necessary to cope with the disease. In order to accomplish its mission, MyPal will exploit technological advances in digital health to support patients, family members and healthcare providers in gaining value through this systematic and comprehensive PRO-based intervention. Overall, the foreseen advancement through MyPal reflects a paradigm shift from passive patient reporting based on conventional PRO approaches to active patient engagement and a closed-loop approach (bridging the gap between patient reporting and effective actions by healthcare providers to meet the varying patient needs) for coping with palliative care challenges in cancer. MyPal will demonstrate and validate the proposed intervention in two clinical studies, an RCT for adults with hematologic cancers and an observational study for children suffering from solid tumors and hematologic malignancies, hence targeting different age groups and cancer types. The clinical studies will be conducted in diverse healthcare settings in 6 clinical sites from 5 European countries.

Contact
Vassilis Koutkias
E-mail: vkoutkias@certh.gr
Tel: +302311257615

Microenvironment and transcriptional regulation in chronic lymphocytic leukemia: focus on the transcription factor TAp63 and its role on the anti-apoptotic phenotype of the leukemic cells.

Funding: NSRF – «Researchers support with focus in young researchers»

Chronic lymphocytic leukemia (CLL) is the most common adults’ leukemia in western countries and, despite the major scientific progress, it remains incurable. CLL is a malignancy of B lymphocytes and displays considerable biological and clinical heterogeneity. In our recent study of a well characterized group of CLL patients we demonstrated that TAp63, the prevalent isoform of transcription factor TP63 in Chronic Lymphocytic Leukemia (CLL), is overexpressed in patients with aggressive clinical course. Additionally, ex vivo downregulation of this transcription factor induced apoptosis of the leukemic cells. Also, we noted that TAp63 expression was modulated by both immune signaling and epigenetic modifications. In the present study we will investigate the exact role of the transcription factor TAp63 in CLL, searching for the molecular mechanisms that takes part and acts as a pro-survival gene, with the final aim of identifying new potential therapeutic targets.

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

Nikos Papakonstantinou
E-mail: npapakonstantinou@certh.gr
Tel: 2311 257 525

Immunogenetic and functional analysis of the B-cell receptor in Monoclonal B-cell Lymphocytosis (MBL) and Chronic Lymphocytic Leukemia (CLL): implications for disease ontogeny

Funding: Hellenic Foundation for Research & Innovation (H.F.R.I.). https://www.elidek.gr/en/homepage/

CLLon aims at dissecting the processes related to the B-cell receptor immunoglobulin (BcR IG) that occur throughout the natural history of CLL and contribute to disease ontogeny and evolution through in-depth immunogenetic and functional studies of the clonotypic BcR IG.
To reach solid conclusions, the study group will comprise individuals with MBL of both subtypes: (i) low-count MBL (LC-MBL) and (ii) high-count MBL (HC-MBL), as well as patients with CLL with distinct clinical courses, ranging from ultra-stable (asymptomatic for at least 10 years) to rapidly progressive. A multiparametric characterization of the BcR properties in MBL and CLL will be performed at different levels: (i) IG heavy and light chain sequence composition, (ii) BcR reactivity profile and (iii) (classical and autonomous) BcR signaling capacity.

Contact
Andreas Agathangelidis, Post-doc researcher
E-mail:
Tel:

Blocking the aggregation promoting ATXN1Q82-MED15 protein-protein interaction.

Funding: HFRI
Spinocerebellar ataxia type-1 (SCA1) is an autosomal dominant and lethal neurodegenerative disorder characterized by progressive movement disorders. It belongs to the group of polyglutamine (polyQ) diseases. It is caused by trinucleotide (CAG) expansions in the coding region of ataxin-1 (ATXN1) gene resulting in polyQ chains in the relevant protein. The mutant protein misfolds into toxic oligomers and forms intranuclear aggregates that cause neurodegeneration in the cerebellum. We have previously shown that the interaction between mutant ATXN1 and MED15 promotes polyQ protein aggregation and proteotoxicity. Therefore, suppressing ATXN1-MED15 protein-protein interaction (PPI) may rescue neurons from cell death. Here, we aim to identify the exact PPI site between ATXN1 and MED15 and block it with chemical compounds having a similar structure. These compounds may also suppress polyQ protein aggregation and reduce cytotoxicity. To minimize the experimental workload, we are going to use a combination of computational and experimental techniques. First, we aim to predict the ATXN1-MED15 PPI site using a protein-protein docking algorithm. This prediction will be validated in a quantitative cell-based PPI assay. Then, we are going to perform a virtual screening and select chemical compounds that have similar structure to the ATXN1-MED15 PPI site. These compounds will be tested whether they block ATXN1-MED15 PPI in cell-based assays. Finally, hit compounds will be tested whether they suppress MED15-mediated ATXN1Q82 protein aggregation in a novel stem cell model using automated high-content screening. We expect that compounds blocking ATXN1-MED15 PPI would also suppress polyQ protein aggregation in primary human cells. Such compounds would be candidates for the development of novel anti-aggregating drugs in polyQ diseases.

Contact
Spyros Petrakis
E-mail: spetrak@certh.gr
Tel: +30 2311 257527

Ανοσογενετική ανάλυση με μεγάλης κλίμακας αλληλούχηση νέας γενιάς ασθενών με Χρόνια Λεμφοκυτταρική Λευχαιμία που ανήκουν στο κλινικά επιθετικό στερεότυπο υποσύνολο #2 και ανοσογενετικά παρεμφερών περιπτώσεων

Φορέας Χρηματοδότησης: GILEAD SCIENCES HELLAS LTD
Η παρούσα μελέτη έχει ως αντικείμενο την ανοσογενετική ανάλυση ασθενών με Χρόνια Λεμφοκυτταρική Λευχαιμία (ΧΛΛ) που ανήκουν στο κλινικά επιθετικό στερεότυπο υποσύνολο #2 και το συγγενές υποσύνολο #169. Επιμέρους στόχοι της προτεινόμενης έρευνας είναι: (α) ο ενδελεχής χαρακτηρισμός του προτύπου των σωματικών μεταλλάξεων στα κλωνοτυπικά γονίδια των ανοσοσφαιρινών και (β) η αναγνώριση επαναλαμβανόμενων μεταλλάξεων με πιθανό αντίκτυπο στη λειτουργία του Β κυτταρικού υποδοχέα. Η προτεινόμενη μελέτη θα συμβάλλει στην αναβάθμιση των γνώσεών μας για την οντογένεσης της ΧΛΛ και στην πληρέστερη κατανόηση της κλινικής συμπεριφοράς του στερεότυπου υποσυνόλου #2, το οποίο αντιπροσωπεύει μια από τις πιο επιθετικές υποομάδες ΧΛΛ.

Contact
Αναστασία Χατζηδημητρίου
E-mail: achatzidimitriou@certh.gr
Τηλ: 2310 498 474

Funding: IMI, EFPIA

Blood cancers, or haematologic cancers (e.g. leukaemia, lymphoma and myeloma), affect the production and function of blood cells and account for about one third of cancer cases in children and about one third of cancer deaths. As many blood cancers are rare, and healthcare practice varies across EU, a lack of data on relevant outcomes represents a challenge for clinicians, researchers, and decision-makers alike.

The HARMONY project aims to use ‘big data’ to deliver information that will help to improve the care of patients with these diseases. Specifically, the project will gather together, integrate and analyse anonymous patient data from a number of high quality sources. This will help the team to define clinical endpoints and outcomes for these diseases that are recognised by all key stakeholders. Meanwhile the project’s data sharing platform will facilitate and improve decision making for policy makers and clinicians alike to help them to give the right treatment to the right patient at the right time. More broadly, the project will result in a pan-European network of stakeholders with expertise in this disease area.

The project is part of IMI’s Big Data for Better Outcomes programme, which aims to facilitate the use of diverse data sources to deliver results that reflect health outcomes of treatments that are meaningful for patients, clinicians, regulators, researchers, healthcare decision-makers, and others.

INAB-CERTH is active within HARMONY both as an associated member but also thanks to its participation in ERIC, the European Research Initiative on CLL, full partner of this project.

Webpage: https://www.harmony-alliance.eu

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

Primary HPV screening based on molecular assessment on self-collected cervicovaginal samples from women with limited access to advanced health services

Funding bodies: Bodossaki Foundation, Roche SA

Genital infection by the human papilloma virus (HPV) is considered to be a sine qua non condition for development of cervical cancer. Currently more than 200 HPV types have been identified and those infecting the cervix have been categorized according to their oncogenic potential as high-risk (hr), i.e. with sufficient evidence for the causation of cervical cancer, possible high-risk, i.e. with limited evidence for the causation of cervical cancer, and not classifiable as to their carcinogenicity to humans. Specific types of hrHPV can cause cervical cancer, and more than 95% of cervical cancer biopsies contain DNA from hrHPV genomes.
The discovery of the causative relationship between hrHPVs and cervical cancer has led to a re-evaluation of the screening strategies used to prevent this disease. Widespread screening of women with the Papanicolaou test has led to a substantial decrease in incidence and mortality due to cervical cancer in countries where it has been systematically implemented. However, cervical cancer screening methods based on cytology have yielded significantly poorer results in countries where screening was not implemented systematically, especially in the developing world. This has been attributed to various reasons such as low coverage, poor patient compliance or subjective interpretation of the results, in conjunction with factors concerning public health and legal issues.
The fact that hrHPV types are detected in more than 99% of invasive cancer cases and in the vast majority of high-grade pre-invasive cases, has gradually led to the introduction of various molecular biomarkers, such as hrHPV DNA, hrHPV mRNA, or hrHPV oncoproteins, as cervical cancer screening candidates. Such methodologies have been approved by the U.S. Food and Drug Administration (FDA) as a primary technique for cervical cancer screening.
Besides the molecular techniques that aim to provide a better tool for cervical cancer screening than the standard one, i.e. cytology, recently, protocols have been developed in order to improve the sampling collection itself, in order to be more accessible, easy and cost effective than the clinician-based collection method. This alternative method should have as a target group those women not participating in national screening programmes and, especially, women living in low-income settings with poor access to health services.
The GRECOSELF study is grounded on the use of a self-sampling device by underscreened women residing in rural areas of Greece and the identification of hrHPV DNA on the cervicovaginal self-collected samples using a FDA-approved method for primary cervical cancer screening. The aims of the study are (i) to expand cervical cancer screening in populations with limited access to health-care or who do not wish to undergo the usual cervical cancer screening procedures due to various reasons; and, (ii) to assess the acceptability of the novel collection method.
The study will enroll women between 25-60 years old who do or do not attend cervical cancer screening and reside in rural areas of Greece. Approximately 12,700 women will be enrolled over a period of 30 months.

Scientific supervisors:
Theodore Agorastos
Professor of Obstetrics and Gynecology, Aristotle University of Thessaloniki

Kostas Stamatopoulos
Director INAB-CERTH

p63: a novel player underlying clinical aggressiveness in chronic
lymphocytic leukemia, regulated by B cell receptor signaling and linked to NF-‘?’B
activation

Funding Body: Janssen Research & Development LLC

This project is prompted by preliminary results from our group which highlight p63 as a novel pro-survival factor in Chronic Lymphocytic Leukemia (CLL), regulated by B
cell receptor (BcR) signaling and leading to NF-‘?’B activation. Hence, the primary objective of this study is to define and understand the links between immune signaling, p63 and NF-‘?’B deregulation in CLL, which will assist in identifying optimal combinations of signaling inhibitors for a subgroup of patients with adverse prognosis, thus refining patient management.

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

COmbatting disorders of adaptive immunity with Systems MedICine

Funding Body: EC – ΗORIZON 2020, Marie Skłodowska-Curie Innovative Training Networks (ITN/ETN)

COSMIC develops and integrate experimental and computational approaches and establish a unique crossfertilization between oncology and auto-immunity. In addition to transferable skills, the training program focuses on establishing a double expertise in laboratory and computational to address clinical questions. It involves a wide-range of stakeholders: (pre)clinical departments, companies, patient groups, students, and the general public. COSMIC will establish a link with the leading European EASyM and ISBE initiatives, and aims to harmonize systems medicine training throughout Europe by connecting to other EU (Marie Curie systems medicine) training initiatives. Impact: COSMIC (i) significantly improves ESR career perspectives (ii) leads to new public-private collaborations increasing competitiveness for companies; (iii) contributes to future oncology and immunology medical care; (iv) contributes to the EU systems medicine best practices.

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

Dissecting the functional pathways of B cell receptor immunoglobulin in antigen driven mature B cell lymphomas

Funding Body: EC – ΗORIZON 2020, Marie Skłodowska-Curie Individual Fellowships (IF-EF)

The B cell receptor immunoglobulin (BcR IG) is important for the ontogeny and evolution of malignancies of mature B cells (B cell non-Hodgkin lymphomas, B-NHLs), mediating critical interactions with the microenvironment, including recognition of and selection/activation by antigens. Of note, inhibition of BcR IG-mediated signaling has emerged as a highly efficacious treatment mode for these tumors, highlighting their dependence on extrinsic triggering. Nevertheless, open issues abound regarding the precise role of the BcR IG in lymphomagenesis, particularly regarding the range of interactions with antigens and their functional impact on clonal behaviour and patient outcome. IGpath is an original multidisciplinary project combining innovative methodologies with the aim of dissecting BcR IG-related mechanisms and processes implicated in the pathogenesis of mature B-NHLs. The focus will be on splenic marginal zone lymphoma (SMZL) and chronic lymphocytic leukemia (CLL), and monoclonal B lymphocytosis, a pre-malignant condition that is considered as a potential precursor state to CLL. IGpath is grounded on the combination of the applicant’s scientific background and skills with the expertise and infrastructure of the Host, thus guaranteeing the bidirectional transfer of knowledge. Therefore, it is anticipated to lead to novel insight into the fundamental mechanisms of lymphomagenesis, holding the potential to identify novel actionable targets and novel prognostic/predictive biomarkers. Moreover, thanks to a carefully designed research strategy and implementation plan, the applicant will acquire valuable skills in novel techniques, project management, and networking, thus setting the basis for an independent career in science

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

Search for TP53 Mutations in Chronic Lymphocytic Leukemia Patients

Funding Body: GILEAD SCIENCES HELLAS LTD

In chronic lymphocytic leukemia (CLL), TP53 gene defects, due to deletion of the 17p13 locus and/or mutation(s) within the TP53 gene, are associated with resistance to chemoimmunotherapy and a particularly dismal clinical outcome. On these grounds, molecular analysis of TP53 aberrations has been incorporated into routine clinical diagnostics to improve patient stratification and optimize therapeutic decisions. Within this context, the aim of this project is to offer state-of-the-art molecular diagnostics of TP53 mutations for CLL patients in need for treatment with the aim of tailoring treatment decisions, along the lines of precision medicine.

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

Heads Lab Services

Funding Body: Health Data Specialist IRELAND LIMITED

INAB-CERTH will perform during the study the following assessments:
1. NGS Immunoprofiling experiments
2. WES experiments
3. RNA seq experiments
4. Peptide pools. Functional T cell assays

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

Anastasia Chatzidimitriou
E-mail: achatzidimitriou@certh.gr
Tel: 2310 498 474

Data management and analysis in hematologic malignancies

Funding Body: Novartis (Hellas) S.A.C.I.

Development of bio-informatics tools and databases for the analysis, interpretation and management of results in hematologic malignancies

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

Sensing and predictive treatment of frailty and associated co-morbidities using advanced personalized models and advanced interventions

Funding Body: EU – HORIZON 2020 – Personalizing Health and Care

Ageing population is steeply increasing worldwide. A consequence of age related decline is the clinical condition of frailty. Frailty is a biological syndrome of decreased reserve and resistance to stressors, resulting from cumulative declines across multiple physiologic systems and causing vulnerability to adverse outcomes. Susceptibility to stressors is influenced by biological, behavioral, environmental, and social risk factors, with the main consequence being an increased risk for multiple adverse health outcomes, including disability, morbidity, falls, hospitalization, institutionalization, and death. However, frailty is a dynamic and not an irreversible process; it seems preventable, may be delayed, or reversed. Our understanding of frailty has markedly improved over the last five years, yet there are many issues yet to be resolved. FrailSafe aims to better understand frailty and its relation to co-morbidities; to identify quantitative and qualitative measures of frailty through advanced data mining approaches on multiparametric data and use them to predict short and long-term outcome and risk of frailty; to develop real life sensing (physical, cognitive, psychological, social) and intervention (guidelines, real-time feedback, AR serious games) platform offering physiological reserve and external challenges; to provide a digital patient model of frailty sensitive to several dynamic parameters, including physiological, behavioural and contextual; this model being the key for developing and testing pharmaceutical and non-pharmaceutical interventions; to create “prevent-frailty” evidence-based recommendations for the elderly; to strengthen the motor, cognitive, and other “anti-frailty” activities through the delivery of personalised treatment programmes, monitoring alerts, guidance and education; and to achieve all with a safe, unobtrusive and acceptable system for the ageing population while reducing the cost of health care systems.

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

Medical Genomics and Epigenomics Network

Funding Body: EU – HORIZON 2020 – COORDINATION AND SUPPORT ACTIONS (CSA)

The main goal of MEDGENET consortium is to use synergies and existing expertise in EU leading institutions such as EMBL, Uppsala University and CERTH to reinforce the productivity and competitiveness of the CEITEC in the field of medical genomics and epigenomics. We propose clear strategy based on combination of unique complementary skills present in partner institutions that will transform CEITEC into a key leader in the field. ERA Chair who recently joint CEITEC already initiated the transformational change of the institute and TWINNING framework will further support sharing her international contacts with other CEITEC researchers. MEDGENET aims to create well-educated taskforce of biomedical researchers, who will notably contribute to the development of new genomics and bioinformatics tools and their application in clinical practice. Proposed project will enable to establish the best practices for performing innovative and high-quality biomedical research and to strengthen CEITEC´s competence to translate the research results into high value-added clinical applications. Stimulation of knowledge exchange, implementation of cutting edge technologies and mastery of modern genomics and bioinformatics methodologies will have a direct impact on the overall research and innovation potential of CEITEC and will increase its visibility in the international scientific community.

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

Innovative risk assessment for individualizing treatment in chronic lymphocytic leukemia

Funding Body: ΕC – ΗORIZON 2020, Marie Skłodowska-Curie Individual Fellowships (IF-EF) 2015 (MSCA-IF-2015-EF)

Τhe scientific proposal CLLassify was successfully evaluated within the framework of the European Actions Marie Skłodowska-Curie Individual Fellowships IF-EF (MSCA-IF-2015-EF). The proposal with full name “Innovative risk assessment for individualizing treatment in chronic lymphocytic leukemia” was submitted by the Postdoctoral Researcher, Dr. Theodoros Moysiadis (fellow), under the supervision of the Director of the INAB, Dr. Kostas Stamatopoulos (Supervisor-Coordinator). The funding of the program refers to the period 2016-2018. The high evaluation of the proposal reflects both its scientific excellence and the dynamic of INAB in a pan-European level.
CLLassify is a highly innovative project that aspires to face the high-challenging and timely problems related to chronic lymphocytic leukemia, and in particular the classification and efficient prognosis of patients at the time of diagnosis and the attempt to personalize the treatment. CLLassify addresses these issues in a pioneering fashion within a multidisciplinary collaboration, proposing an improved classification of the patients, based on innovative statistical techniques as well as the novel aspect of personalized prediction of the need for treatment at a specific time point for the individual patient.

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

Genetic and cellular intratumor heterogeneity as predictor of chronic lymphocytic leukemia outcome and treatment resistance.

Funding Body: ΕC – ΗORIZON 2020

The clinical course and eventual outcome of Chronic Lymphocytic Leukemia (CLL) patients is highly variable. It is accepted that intratumor genetic and cellular heterogeneity is the main force driving both tumor development and treatment resistance. At the genetic level, there is no single gene mutation characteristic of the disease and CLL cells in a given patient may carry different burden of different mutations affecting different pathways. At the cellular level, leukemic cells remain responsive to multiple stimuli originating from microenvironment but with different intensity and effect. Available biomarkers aiming at predicting both the disease course and the response to treatment exist, but none of the current models capture the complexity of intratumor heterogeneity. Intratumor genetic and cellular heterogeneity of CLL has tremendous implications for treatment and outcome, but is currently poorly understood. Novel means of observing and quantifying this heterogeneity together with integrative and predictive mathematical modeling will help identifying strategies to prevent treatment resistance.

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

Detailed functional characterization of Splenic Marginal Zone Lymphoma:
uncovering molecular and cellular markers for prognosis and treatment
optimization

Funding Body: Janssen Research & Development LLC

Splenic Marginal Zone Lymphoma (SMZL) is a rare chronic B-cell lymphoproliferative
disorder that predominantly affects elderly patients. Although the median survival
is around 10 years, approximately 70% of SMZL patients require treatment for
progressive, symptomatic disease and 5% undergo transformation into a large B-cell
lymphoma.
Despite recent advances in our understanding of Splenic Marginal Zone Lymphoma
(SMZL), the available evidence about therapeutic options is mostly based on
retrospective series or translated from experience in other indolent B-cell
lymphomas. Additionally, tailoring of treatment is limited by the lack of sufficient
pre-clinical information (especially regarding novel agents) and paucity of robust
predictive factors.

SMZL-Ibru-EZH2 aims at:

detailed characterization of immune signaling capacity of SMZL B cells, in order
to obtain deeper insight into the precise role of signaling inhibitors in SMZL
management
screening and functional characterization of EZH2, a marker of clinical
aggressiveness and druggable target in lymphoma, in well a characterized cohort of
SMZL cases
investigation of the effects and potential synergism of combined EZH2 and
signaling inhibition in SMZL cells ex vivo

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

TP53 Mutant Microclones in CLL – Implementation Of A Robust NGS – Based Detection Workflow And Investigation Of Subclonal Dynamics And Clinical Significance

Funding Body: GILEAD SCIENCES

The project aims at advancing and standardizing the detection of TP53 mutant microclones in CLL by a robust NGS methodology utilizing a large series of well-characterized cases of different progression status and cytogenetic profiles. Ultimately, this will ensure optimal patient care, interaction with clinical study groups and the pharmaceutical industry to focus on this particularly difficult-to-detect biomarker of clinical significance.

Contact
Anastasia Chatzidimitriou
E-mail: achatzidimitriou@certh.gr
Tel: 2310 498 474

Employing NGS technology for improved, non-invasive early detection, staging and prediction of progression in lymphoma patients

Funding Body: ERA-NET: Aligning national/regional translational cancer research programmes and activities, TRANSCAN-2

The project is expected to achieve validated and implemented procedural and analytical pipelines for NGS profiling of B-NHL/CLL-specific biomarkers in liquid biopsies. We will also define validated and implemented bioinformatics workflows and tools for widespread use in a diagnostic setting. The successful completion of the NOVEL proposal will allow to achieve accurate outcome prediction and improved survival through risk stratification of individuals carrying pre-lymphomatous or indolent conditions for evolution to overt lymphoma and refined molecular diagnosis/staging in the aggressive forms. Potentially, the procedural and analytical pipelines could be utilized also for the management of other neoplastic conditions.

Contact
Anastasia Chatzidimitriou
E-mail: achatzidimitriou@certh.gr
Tel: 2310 498 474

Secure and Trusted Paradigm for Interoperable eHealth Services

Funding Body: EUROPEAN COMMISSION, HORIZON 2020, H2020-DS-SC1-2016

KONFIDO advances the state of the art of eHealth technology with respect to four key dimensions of digital security, namely: data preservation, data access and modification, data exchange, and interoperability and compliance. To address the challenges of secure storage and exchange of eHealth data, protection and control over personal data, and security of health related data gathered by mobile devices, KONFIDO takes a holistic approach – i.e. one targeting all the architectural layers of an IT infrastructure, and specifically: storage, dissemination, processing, and presentation. KONFIDO builds on and extends the results of a best of breed selection of successful projects, notably: epSOS, STORK, DECIPHER, EXPAND, and ANTILOPE. The approach will be implemented in a technological framework that relies on six technology pillars: 1) security extensions provided by main CPU vendors; 2) security solutions based on photonic technologies; 3) homomorphic encryption mechanisms; 4) customised STORK-compliant eID support; 5) customized extensions of selected SIEM solutions; and 6) disruptive logging and auditing mechanisms. The usability of the proposed solutions will be tested in a realistic setup, deployed on top of a federated cloud infrastructure, where data will be exchanged and services interoperate cross-border. Experimental evidence will be collected, proving that KONFIDO solutions provide effective protection even against attacks by privileged software (e.g. the Operating System or the Hypervisor) or privileged users (e.g. the System Administrator or the Cloud Provider). Since i) it builds on results that were already widely accepted, and ii) it relies on a handful of complementary technologies (some of which are already at a high level of maturity), KONFIDO has a dramatic potential in terms of innovation in the field of coordinated care towards improved quality of healthcare solutions.
Web site: https://konfido-project.eu/

Contact
Vassilis Koutkias
E-mail: vkoutkias@certh.gr
Tel: 2311 257 615

Joint Action on integrating prevention, testing and link to care strategies across HIV, Viral Hepatitis, TB & STIs in Europe

Funding Body: EUROPEAN COMMISSION, 3rd Health Programme, HP-JA-01-2016

The “Joint Action on integrating prevention, testing and link to care strategies across HIV, Viral Hepatitis, TB & STIs in Europe” (INTEGRATE) has the overall objective to increase Integrated early diagnosis and linkage to prevention and care of HIV, viral hepatitis, TB and STIs in EU Member States by 2020. A number of tools have been developed to reduce transmission, optimize early diagnosis and linkage to care for one or more of these four diseases. INTEGRATE will map relevant existing tools for cross-linking. A peer-review process will identify which of these tools are complimentary or redundant for other disease(s), and which could be adapted or require further innovation. HIV, viral hepatitis, TB and STIs are cross-borders public health threats of concern to Europe that affect vulnerable populations disproportionately and require personalised interventions. As multiple dimensional approaches are required to reduce the public health burden, the most optimal profile of approaches that provide additive effects (and that are reasonably cost-effective) should be identified and implemented broadly. INTEGRATE provides a platform to disseminate and exchange best practice among Member States and facilitate discussions on innovations and emerging issues within the four diseases. In this respect, INTEGRATE is a shared European effort that extends beyond the partners and can create important synergies across European stakeholders, projects and initiatives. INTEGRATE supports the implementation of the Commission Communication on ‘Combating HIV/AIDS in the European Union and neighboring countries’ and the ‘Action Plan on HIV/AIDS in the EU and neighboring countries’ by ensuring better preparedness across the EU and by identifying innovative evidence-based testing and prevention tools to reduce new cases of HIV, viral hepatitis, TB and STIs in priority groups.
Web site: https://IntegrateJA.eu/

Contact
Vassilis Koutkias
E-mail: vkoutkias@certh.gr
Tel: 2311 257 615

Implementing good practices for chronic diseases

Funding Body: EUROPEAN COMMISSION, 3rd Health Programme, HP-JA-02-2016

Europe is paying a heavy price for chronic diseases (CD): it has been estimated that CD cost EU economies 115 billion € or 0.8% of GDP annually; and this figure does not include the additional loss in terms of lower employment rates and productivity of people living with chronic health problems. However, the aspiration is a health-promoting Europe, free of preventable CD, premature death and avoidable disability could be possible. Initiatives on CD should build on four cornerstones: health promotion and primary prevention as a way to reduce the burden of CD; patient empowerment; tackling functional decline and quality of life as the main consequences of CD, and making health systems sustainable and responsive to the aging of our populations associated with the epidemiological transition (an increase in incidence of CD and extended life expectancy) whose consequence is an increasing prevalence of CD. In this Joint Action, CHRODIS-PLUS, our goal is to support Member States through cross-national initiatives identified in JA-CHRODIS to reduce the burden of CD, while assuring health systems sustainability and responsiveness. CHRODIS-PLUS aims to promote the implementation of policies and practices with demonstrated success in each of the four cornerstones mentioned, in closely monitored implementation experiences that can be validated before scaling them up. For this, a total of 42 beneficiaries representing 20 European countries will collaborate to implement pilots and generate practical lessons that could contribute to the uptake and use of CHRODIS-PLUS results. Practices to be implemented will be based on the collection of policies, strategies and interventions that started in JA-CHRODIS and in its outputs such as the Integrated Multimorbidity Care Model or the Recommendations for Diabetes Quality criteria or national plans. During the 36-month life CHRODIS-PLUS will disseminate its activities and monitor and evaluate them to verify the progress and impact of the action. CHRODIS-PLUS will look for synergies with international/ regional/local policy initiatives in CD. CHRODIS-PLUS will count on the Governing Board of representatives from European Ministries of Health, key to CHRODIS-PLUS development and sustainability, an Executive Board and a General Assembly where all associated partners will gather. A proposal for the EU added value of cross-country collaboration in the field of CD and the sustainability of the results from JA-CHRODIS and CHRODIS-PLUS beyond 2020, when this project ends, will be approved.
Web site: https://chrodis.eu/

Contact
Vassilis Koutkias
E-mail: vkoutkias@certh.gr
Tel: 2311 257 615

Maximising Impact of research in NeuroDevelopmental DisorderS

Funding Body: CA COST Action CA16210

This Action focuses on patients with rare neurodevelopmental disorders (NDD) whose study have the potential for major impact on our understanding and treatment of NDD in general, including schizophrenia and Autism Spectrum Disorder (ASD). NDD affect 1 in 25 individuals in Europe, and have high impact on healthcare systems, economic development and society. Lack of mechanistic knowledge hampers development of improved treatments. New knowledge from psychiatric genomics provides for the first time a route to identify neurobiological mechanisms underlying NDD. The key challenge is to link genetic risk to altered brain biology.
Although highly informative, substantial variability and severity of psychiatric symptoms means that genomic studies based on the general NDD patient population experience significant difficulties in assigning individual gene mutations to clinical phenotype. A solution to this challenge is the study of subgroup of NDD patients where deletions or duplications of DNA segments (Copy Number Variants, CNV) alter gene dosage and have a strong causal relationship with NDD. These pathogenic CNV present a major opportunity to establish mechanistic understanding and develop new therapies. However, NDD patients with these CNV are rare and require a coordinated, international collaboration to find and study them in large numbers.
MINDDS will create a pan-European network of clinical scientists, preclinical researchers and patient representatives to advance studies of NDD patients for these pathogenic CNV. It will create a legal and ethical framework for effective transnational NDD patient cohort building; develop standardized protocols and establish effective mechanisms for effective data sharing and knowledge exchange.
Web site: https://www.cost.eu/COST_Actions/ca/CA16210

Contact
Vassilis Koutkias
E-mail: vkoutkias@certh.gr
Tel: 2311 257 615

Spyros Petrakis
E-mail: spetrak@certh.gr
Tel: 2311 257 527

Mechanisms of action of the methyltransferase EZH2 in Chronic Lymphocytic Leukemia

Funding Body: GILEAD SCIENCES HELLAS LTD

We have recently identified the histone methyltransferase EZH2 as a new therapeutic target in Chronic Lymphocytic Leukemia (CLL).
Moreover, we have showed that microenvironmental stimuli further augment EZH2 protein expression. In this study we will investigate how EZH2 affect CLL cell behavior.
The aims of this study include: i) clarification of EZH2 impact on CLL cells at molecular level and ii) study of how microenvironmental stimuli affect EZH2 function.

Contact
Nikos Papakonstantinou
E-mail: npapakonstantinou@certh.gr
Tel: 2311 257 525

Ανοσογενετική ανάλυση υγιών ατόμων με/χωρίς μονοκλωνική Β λεμφοκυττάρωση: οντογενετικές προεκτάσεις για τη χρόνια λεμφοκυτταρική λευχαιμία

Φορέας Χρηματοδότησης: GILEAD SCIENCES ΕΛΛΑΣ Μ.Ε.Π.Ε.

Η ανάπτυξη της τεχνολογίας αλληλούχησης νέας γενιάς έχει βοηθήσει σημαντικά στη βελτίωση της κατανόησης της βιολογίας της χρόνιας λεμφοκυτταρικής λευχαιμίας (ΧΛΛ). Όμως, σημαντικά ερωτήματα παραμένουν όσον αφορά την προέλευση της νόσου. Το ρεπερτόριο των Β κυτταρικών υποδοχέων σε ασθενείς με χρόνια λεμφοκυτταρική λευχαιμία (ΧΛΛ) χαρακτηρίζεται από την παρουσία υποσυνόλων ασθενών που εκφράζουν σχεδόν πανομοιότυπες, «στερεότυπες» αναδιατάξεις. Σκοπός της προτεινόμενης εργασίας είναι η ανίχνευση ΧΛΛ-εδικών, «στερεότυπων» αναδιατάξεων σε υγιείς δότες με μονοκλωνική Β λεμφοκυττάρωση (ΜΒΛ). Η παρουσία «στερεότυπων» αναδιατάξεων θα υποδείκνυε ότι η πίεση επιλογής στα συγκεκριμένα Β λεμφοκύτταρα θα μπορούσε να αποτελεί έναν από τους παράγοντες εμφάνισης της ΧΛΛ.

Επικοινωνία
Ανδρέας Αγαθαγγελίδης,
Email: aagathangelidis@certh.gr,
Τηλ: 2311 257 525

Past Projects

CLL patient empowerment for active participation in decision-making

Funding Body: Janssen-Cilag Greece and Gilead Sciences Hellas

Society is faced with a massive health and social care challenge: in addition to demographic changes that will see the proportion of those over 60 years of age rise dramatically in coming years, we will face unmanageable costs associated with the increased prevalence of non-communicable diseases (NCD). This, combined with a global shortage of qualified healthcare professionals, highlights the need to find new ways of managing health and social care. Focusing on CLL, we aim to lay the cornerstone for a novel paradigm in NCDs’ management through patient empowerment for active participation in decision-making by: (i) providing multi-level support to patients and caregivers during the course of the disease; and (ii) designing a special training program to guide health professionals through different disease time-points (diagnosis, treatment initiation, breaking bad news etc) and different behavioral responses (non-adherence, denial etc).

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

HEM 2017 ERIC patient empowerment program

Funding Body: JANSSEN PHARMACEUTICA EMEA

HEM 2017 ERIC Patient Empowerment framework aims to achieve:
improved interaction between patients, caregivers and healthcare professionals, facilitating the stratification and active participation of patients in disease management processes
reinforced medical knowledge with respect to efficient disease management
increased confidence in decision support systems for disease/patient management
increased and accurate level of education, knowledge and acceptance by patients and healthcare professionals of ICT solutions for personalized care
reduced admissions in care institutions as a result of improved disease management and treatment at the point of need
reduced absences from work for patients as well as their caregivers and improvements in the daily activities of patients
empowerment of patients towards active participation in disease management, which may possibly inspire them into a more active participation in society as well: more active patients is synonymous to more active citizens, more active professionals, more active parents, more active friends.

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

Funding Body: Lymphoma Coalition (LC)

In early 2008, Lymphoma Coalition (LC) launched its first Global Patient Survey to its member organisations. This has since occurred every two years since. It is imperative that we understand the patient experience in lymphomas and CLL in order to manage their care the best as possible as well as understand the impact of treatment and care. Through this survey, LC and its global members can respond to the results and bring the patient voice forward.

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

An analytics framework for integrated and personalized healthcare services in Europe

Funding Body: EU
HORIZON 2020 – INNOVATION ACTIONS (IA)

AEGLE (Ancient Greek: Αἴγλη)

AEGLE aims to generate value from the healthcare data value chain data with the vision to improve translational medicine and facilitate personalized and integrated care services overall improving healthcare at all levels, to promote data-driven research across Europe and to serve as an enabler technology platform enabling business growth in the field of big data analytics for healthcare.
Web site: https://www.aegle-uhealth.eu

Contact
Vassilis Koutkias
E-mail: vkoutkias@certh.gr
Tel: 2311 257 615

More Information

Technology enabled behavioural change as a pathway towards better self-management of cardio-vascular disease

Funding Body: EU
HORIZON 2020, 2014-2018 42 month project

PATHway will provide individualized rehabilitation programs that use regular, socially inclusive exercise sessions as the basis upon which to provide a personalized comprehensive lifestyle intervention program (exercise/physical activity (PA), smoking, diet, stress management, alcohol use, medication compliance) to enable patients to both better understand and deal with their own condition and to lead a healthier lifestyle in general. This will be made possible by the provision of an internet-enabled sensor-based home exercise platform that allows remote participation in CR exercise programs at any time, by a small number of patients from the comfort of their own living room.
Web site:https://pathway2health.eu

Contact

Vassilis Koutkias
E-mail: vkoutkias@certh.gr
Tel: 2311 257 615

More Information

INdependent LIving support Functions for the Elderly

Funding Body: EU
HORIZON 2020 – INNOVATION ACTIONS (IA)

IN LIFE aims to prolong and support the independent living of seniors with cognitive impairments, through interoperable, open, personalised and seamless ICT solutions that support home activities, communication, health maintenance, travel, mobility and socialisation tasks, with novel, scalable and viable business models, based on feedback from large-scale and multi-country pilot applications.
Web site: https://www.inlife-project.eu

Contact
Vassilis Koutkias
E-mail: vkoutkias@certh.gr
Tel: 2311 257 615

More Information

Molecular and functional analysis of Toll-like receptors (TLR) in acute and chronic graft versus host disease (GvHD) after allogenic hematopoietic cell transplantation in patients with hematologic malignancies

Funding Body: Janssen Pharmaceuticals

The development of methodologies that target exclusively the clinical manifestations of Graft vs Host Disease (GvHD) sustaining the desirable activity against the malignant cells of the recipient and the pathogens, could be a crucial intervention in order to improvement of the survival of patients with hematologic malignancies that undergo allogeneic transplantation. In this study, we will investigate the expression of TLR2, TLR4, TLR5, TLR7 and TLR9 at basal level and after activation with their cognate ligands.

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

Funding Body: Novartis Hellas

Chronic myelogenous leukemia (CML) is a type of cancer that starts in hematopoietic progenitors in the bone marrow. CML is caused by a genetic aberration occurring in an early hematopoietic cell forming an abnormal gene called BCR-ABL, which turns the cell into a CML cell. A landmark in CML clinical research, indeed a milestone in cancer therapy at large, was the development of remarkably efficacious tyrosine kinase inhibitors (TKIs) that target BCR-ABL which have been established as the standard treatment for CML, leading to dramatic improvements in patient outcomes. Advances in CML treatment with the use of TKIs mandate regular updating of concepts and management and, for this reason, the European LeukemiaNet recently updated recommendations for 1st line of treatment, monitoring of response to treatment by molecular and cytogenetic techniques, including definitions for optimal or suboptimal response or even failure.
The CMLab-GR project concerns the establishment of a lab network for clinicobiological data of CML patients from major hematology centers in Greece with the following objectives:
To provide a unified platform with molecular data of CML patients in order to correlate clinical and laboratory data from different medical centers and laboratories
To develop an efficient management system with integration and validation mechanisms and thus eliminating data inconsistency and redundancy and improving data mining, data sharing and statistical analysis
To study the evolution of molecular results overtime in relation to treatment

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

Registry of cases with Chronic Lymphocytic Leukemia (CLL) in Greece

Funding Body: Glaxo SmithKline SA

Creation of a registry of patients with CLL from major hematology centers in Greece aiming at: (a) enabling multi-center projects on clinical association studies, (b) providing accurate information about the state-of-the-art in CLL diagnosis, prognostic assessment and management in Greece and (c) facilitating the design of clinical trials.

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

Understanding mechanisms of clinical aggressiveness and treatment failure in Chronic Lymphocytic Leukemia (CLL) focusing on patients treated with the FCR Regimen: the role of DNA Methylation

Funding Body: Roche S.A.

Study description: 1] DNA methylation profiling of additional CLL patients relapsing after FCR, with a strong focus on cases carrying del11q and cases with stereotyped B-cell receptors. 2] Gene expression profiling using microarrays in paired samples with pronounced DNA methylation changes at diagnosis and relapse and pathway enrichment analysis of differentially methylated and differentially expressed genes. 3] siRNA screens for hypomethylated and over-expressed genes.

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

Immune Signaling in Chronic Lymphocytic Leukemia and Ibrutinib response

Funding Body: Janssen Pharmaceuticals

In this project we will explore two major mechanisms that may underlie less than optimal responses to BcR inhibition by ibrutinib, namely: (i) “bypass” activation from non-BcR immune pathways, in particular the TLRs; and, (ii) resistance to signaling inhibitor-induced apoptosis in a context of BcR anergy associated with decreased dependence on proximal BcR signaling.

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

A multidisciplinary investigation into the pathogenesis of chronic lymphocytic leukemia (CLL) for the identification of novel molecular therapeutic targets

Funding Body: FONAZIONE CARIPLO

In this project, we are aiming at characterizing the interactions occurring with the CLL immunoglobulin receptor that are likely responsible for the clinical-biological behavior of subsets of CLL cases expressing stereotyped BCRs. The specific aims are two-fold: 1) to decipher the nature and identity of the antigen(s) binding to stereotyped receptors, and 2) to characterize the structure of the leukemic stereotyped receptors. Both aims will concur to provide crucial information that will integrate in order to achieve targeted therapeutic strategies for each particular subset of the disease.
The definition of the nature and identity of the binding elements to the leukemic BCR combined with the knowledge about the actual structure of the receptor, will be instrumental to find natural ligands or design compounds that might be used to target CLL cells with therapeutic purposes, either by blocking crucial survival stimuli or by directly inducing apoptosis, or by delivering cytotoxic agents.
The proposed project will take advantage of: a) a multi-disciplinary approach, through the integration of the different yet complementary professional expertise at the two partner institutions, including basic immunology, hematology, biophysics, structural biology and bioinformatics; b) a European based collection of cases with “stereotyped” BCRs, the largest of its kind worldwide, developed as part of a long-standing established co-operative effort which was pioneered by the proponents of research. The integration of research efforts in a way capable of providing a new perspective and added-value to existing infrastructure will allow the proponents of research to make important steps towards obtaining a wider, biologically and clinically relevant, picture of the disease.

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

Complete genotypic and phenotypic analysis of acquired diseases of the hemopoietic tissue: pathogenetic, diagnostic and therapeutic extensions

Funding Body: General Secretariat for Research and Technology of Greece – SYNERGASIA – ACTION 1 – National Strategic Reference Framework 2007 – 2013

The present proposal concerns the support and conduct of an interdisciplinary research on the analysis of “representative” disorders for major disease entities in the field of Hematology.
Chronic Lymphocytic Leukemia (an archetyic lymphoprolipherative disorder) and Chronic Idiopathic Neutropenia (an exemplary of bone marrow deficiencies) are disorders with unclear underlying pathogenic mechanisms and great heterogeneity in terms of clinical presentation, course and final outcome. This proposal aims at the improved fundamental understanding of the aforementioned entities, focusing on genotype-phenotype associations, the recognition of new molecular diagnostic and prognostic markers, and on the identification of new therapeutic targets.
All of the above mainly rely on the synthesis and analysis of clinicobiological data from these representative hematologic disorders, using advanced bioinformatics methods.

Visit ENosAI website

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

Clinical and Molecular Parameters in the Treatment of Chronic Lymphocytic Leukemia

Funding Body: ROCHE HELLAS SA

Contact
Anastasia Chatzidimitriou
E-mail: achatzidimitriou@certh.gr
Tel: 2310 498 474

Funding Body: GILEAD SCIENCES HELLAS LTD

Consulting services on recent developments in the biology and treatment of hematologic malignancies, preparation of educational material on B cell biology and B cell neoplasia and relevant educational initiatives.

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

TP53 mutation screening in Chronic Lymphocytic Leukemia patients

In chronic lymphocytic leukemia (CLL), TP53 gene defects, due to deletion of the 17p13 locus and/or mutation(s) within the TP53 gene, are associated with resistance to chemoimmunotherapy and a particularly dismal clinical outcome. On these grounds, molecular analysis of TP53 aberrations has been incorporated into routine clinical diagnostics to improve patient stratification and optimize therapeutic decisions. Within this context, the aim of this project is to offer state-of-the-art molecular diagnostics of TP53 mutations for CLL patients in need for treatment with the aim of tailoring treatment decisions, along the lines of precision medicine.

Funding Body: GILEAD SCIENCES HELLAS LTD

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

Design and development of a database of biological and clinical data and a data entry system

Funding Body: ROCHE HELLAS SA

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

Epigenetic modifications of the genome in patients with haematological malignancies.

Funding Body: NOVARTIS HELLAS S.A.C.I.

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

Functional annotation and comparative analysis of genome sequences

Funding Body:

Contact
Kostas Stamatopoulos
E-mail: kostas.stamatopoulos@certh.gr
Tel: 2310 498 271

Molecular profiling of the Immunoglobulin Gene Repertoire with Next Generation Sequencing in HIV-associated B cell lymphoproliferations

Funding Body: GILEAD SCIENCES HELLAS LTD

The risk of developing a lymphoproliferative disorder is increased with immunosuppression of any cause, whether congenital, acquired through infection with the human immunodeficiency virus (HIV) or following solid organ transplant, hematopoietic stem cell transplant or pharmacological immunosuppression for autoimmune disorders. The heterogeneity of HIV?associated lymphoproliferations reflects several pathogenetic mechanisms: chronic antigen stimulation, genetic abnormalities, cytokine deregulation and the role of the Epstein Barr virus (EBV) and the Human Herpes Virus 8 (HHV8); however EBV?positive lymphomas decreased in the HAART era. Studies over the past two decades have established that immunogenetic analysis can offer important insight into the ontogeny and evolution of B cell lymphoproliferations. In particular, the presence of somatic hypermutation (SHM) in the clonotypic immunoglobulin (IG)
receptors is widely considered as evidence of affinity maturation within the context of antigen encounter, while IG gene repertoire are regarded as a “molecular signature” of selection by antigen. However, the analytical depth afforded by Sanger sequencing is limited, hindering definitive conclusions.


Contact
Anastasia Chatzidimitriou
E-mail: achatzidimitriou@certh.gr
Tel: 2310 498 474

Development of an electronic platform for the data registration of patients with Chronic Lymphocytic Leukemia

The purpose of this project was the creation of a data registration platform for clinicobiological data of patients with Chronic Lymphocytic Leukemia (CLL) in order to (a) enable multi?center projects on clinical association studies, (b) provide accurate information about the state of the art in CLL diagnosis, prognostic assessment and management in Greece and (c) facilitate the design of clinical trials. The steps in order to design and develop the CLL registry included a number of meetings with scientists, clinicians and technicians involved in the diagnosis and treatment of CLL patients. Exchange of information leaded to the selection of the data types to be collected, the description and organization of the data categories and furthermore the description of the data relationships in order to define rules and constraints and design the database in a way to allow and facilitate data correlations. Based on the acquired information and the system design, the following steps were the implementation in the data catalogue, the design of template spreadsheets for the data registration and a relational database design and development for the data organization and storage. The collection and curation of data were designed by using semi?automated methods according to the defined rules and constraints. The final version of the registration system helped with the collection of test data that were used in order to validate database analytics.

Funding Body: GILEAD SCIENCES HELLAS LTD

Contact
Anastasia Chatzidimitriou
E-mail: achatzidimitriou@certh.gr
Tel: 2310 498 474

Chronic Lymphocytic Leukemia (CLL) leukemic B cells are highly dependent on signals emanating from the microenvironment and received by their immune receptors, for their survival and proliferation. The present study focused on the analysis of the signaling capacity through the B cell receptor and the Toll-Like Receptors in subgroups of CLL patients with different clinical course, aiming to identify a distinct biochemical signature for each group of patients. By correlating the biochemical data with patient clinicobiological data we will investigate if these biochemical signatures have prognostic power for differential responses to therapy with signaling inhibitors.

Funding Body: GILEAD SCIENCES HELLAS LTD

Contact
Stavroula Ntoufa
E-mail: sntoufa@certh.gr
Tel: 2310 498 472

Ecosystem infrastructure for smart and personalised inclusion and PROSPERITY for ALL stakeholders

Funding Body: EU
7 F.P. – Collaborative Project (CP)

Over 2 billion people worldwide have different types, degrees, or combinations of disability, literacy, digital literacy or aging related barriers that impede or prevent use of ICT. Not long ago you could live without access to ICT quite well. However today access to ICT is required for most education, employment, and commerce, and is increasingly required for travel, health, safety, daily living and participation in most of our society. Yet we currently only reach 3 to 15% of these – in developed countries. We cannot socially, economically or politically afford to have this cumulatively large percentage of our society offline going forward. Yet there is no way to reach them with our current model. Proposed is phase II of an effort to create a paradigm shift in eInclusion. Part I was the FP7 project Cloud4all for creating instant, ubiquitous auto-personalization of interfaces and materials based on user needs and preferences. Part II, Prosperity4all, focuses on developing the infrastructure to allow a new ecosystem to grow; one that is based on selfrewarding collaboration, that can reduce redundant development, lower costs, increase market reach and penetration internationally, and create the robust cross-platform spectrum of mainstream and assistive technology based access solutions required. This will be done through a process based on true value propositions for all stakeholders and resulting in a system that can profitably serve markets as small as one, at a personally and societally affordable cost. This infrastructure will use cloud, crowd, game and smart technologies, to bring new players with both low and high technical skills into the development and delivery ecosystem, introduce accessibility as a ubiquitous service, and combine auto-configured access features built into mainstream products with assistive technologies and services to create the rich milieu of options needed to bring this diverse population of populations into our digital future.
Web site:https://www.prosperity4all.eu

Contact

Nicos Maglaveras
E-mail: nicmag@certh.gr
Tel: +302310999281

More Information

Cloud platforms Lead to Open and Universal access for people with Disabilities and for All

Funding Body: EU
7 F.P. – Collaborative Project (CP)

As we move more inextricably into a digital economy there is a looming crisis for a growing number of increasingly marginalized individuals. The accessibility technologies we have are meeting the needs of only some, at high cost – and will not work with many new technologies. In addition, the pace and path of technological change predestines these approaches to fail in the very near future. At the same time the incidence of disabilities is increasing as our population ages. The same technical advances however hold the key for a radical paradigm shift in our approach to accessibility that can harness the pace of innovation and have it work for us rather than against us. The Cloud4All project taps the unprecedented ability to pool resources and match demand with supply enabled by the Cloud to deliver accessibility to every individual where they need it, when they need it and in a way that matches their unique requirements; automatically so that they do not need to negotiate, explain, qualify or justify. Cloud4All pulls together a large multi-sector international community including stakeholders, industry leaders and experts in emerging technologies to thoughtfully design, research and develop the necessary software infrastructure, pilot implementation and evaluation needed to explore this promising approach to digital inclusion. The project will test this with a wide range of delivery options, contexts and platforms including auto-personalization of different OSs, browsers, phones, web apps, kiosks, ITMs, DTVs, smart homes and assistive technologies (cloud and installed). This approach can enable us to reach the large group of users that do not qualify for or choose not to avail themselves of special services but nonetheless face barriers to access, including individuals with literacy challenges and individuals who are aging. Cloud4All will create a sustainable system that ensures that all individuals can participate in our rapidly advancing digitally enabled society.

Contact

Nicos Maglaveras
Email: nicmag@certh.gr
Tel: +302310999281

More Information