BIO-MEDICAL RESEARCH

Bio-Medical Research Projects

Biomedical Research at INAB|CERTH revolves around the dissection of disease pathogenesis and the development and validation of innovative methodologies, products and services of medical interest in order to facilitate the transition “from bench to bedside”, in line with the concept of precision medicine for maximizing benefits while at the same time minimizing unnecessary costs and toxicities.

Main focus areas and objectives include:

  • to dissect cancer pathophysiology and identify novel predictive biomarkers and novel therapeutic targets
  • to improve cancer prevention, diagnosis and prognostication
  • to integrate, analyze and interpret different types of biomedical data
  • to develop validated applications for facilitating the collection of real world evidence for patients with non-communicable diseases

INAB | CERTH is one of four nodes in the Precision Medicine Network (PMN) recently established (2018) by the Division for Research and Innovation of the Ministry of Education, Research and Religious Affairs of Greece.

The particular omics studies and related computational approaches currently in progress within INAB|CERTH fall in the biomedical domain include:

1. High throughput immunogenetic analysis in health and disease: Immunoglobulin Gene Repertoire Profiling in Lymphomas and pre-lymphomatous states; T cell Receptor Gene Repertoire Profiling in Lymphomas, Bone Marrow Failure Syndromes, chronic Graft Versus Host Disease, Infections, Autoimmune Disorders; Effects of novel drugs on the tumor microenvironment in hematologic malignancies
2. Integrated omics analysis of hematologic malignancies: DNA methylome and Transcriptome Profiling in patients with hematologic malignancies treated with chemotherapy versus novel agents; Whole exome sequencing of pre-malignant conditions
3. Targeted NGS analysis for improved risk stratification in cancer: novel recurrent gene mutations in hematologic malignancies
4. NGS based analysis of human viruses: NGS analysis of methylation patterns in HPV serotypes
5. NGS analysis of methylation patterns in genes involved in type I diabetes
These studies are complemented by extensive characterization of the findings at both the genetic level (established workflows for gene editing by the CRISPR/Cas9 system, RNA interference and the Sleeping Beauty Transposon approach); and, the cellular/biochemical level.

INAB | CERTH is very active in initiatives related to the standardization and harmonization of diagnostic techniques. Its activities aim to promote and/or advance the assessment of biomarkers for diagnostic purposes through education, standardization of procedures and workflows and the publication of guidelines. Ultimately, this will improve optimal patient care and will increase the availability of relevant tests, allowing clinical study groups, as well as the pharmaceutical industry, to focus on these particularly difficult-to-treat patients and channel them to clinical trials aimed at further improving long-term outcomes.
In more detail, INAB | CERTH:

• supervised the formulation of international recommendations for the determination of the somatic hypermutation status in chronic lymphocytic leukemia (https://www.ncbi.nlm.nih.gov/pubmed/28439111)
• participated in the formulation of international recommendations for the detection of TP53 gene defects in hematologic cancer (https://www.ncbi.nlm.nih.gov/pubmed/29467486)
• participates in the assessment and ranking of clinically relevant mutations in lymphomas (https://www.ncbi.nlm.nih.gov/pubmed/27582569)
• develops free software for bioinformatics analysis for use in a clinical diagnostic setting (https://www.ncbi.nlm.nih.gov/pubmed/26249808; https://www.ncbi.nlm.nih.gov/pubmed/29036643)

INAB | CERTH is an active node in BBMRI-ERIC, the Biobanking and BioMolecular resources Research Infrastructure – European Research Infrastructure Consortium [https://directory.bbmri-eric.eu/menu/main/dataexplorer/details/eu_bbmri_eric_collections/bbmri-eric:ID:GR_clINABdb:collection:all_samples]
In this context, it collaborates in the collection, processing and storage of primary biological material from patients (patient samples) with the Hematology Department and HCT Unit of the G. Papanicolaou Hospital, Thessaloniki, Greece, under a Memorandum of Understanding.

Real-world evidence (RWE) research is an increasingly important component of biopharmaceutical product development and commercialization. RWE also has the potential to improve the quality and delivery of medical care, reduce overall costs and improve outcomes by accelerating the understanding of how best to incorporate new therapies and technologies into everyday clinical practice.
At INAB |CERTH we have developed a standardized and centralized biomedical data repository and management system for RWE in cancer, with a strong focus on hematologic malignancies, that enhances the power of analysis, allowing unified access, thus improving research and clinical routine efficiency and quality on multiple levels. Since the amount of available biomedical and genomic data is continuously increasing due to technological advances, we employed new methodologies and data management systems to allow creation of data warehouses with high-quality data.
INAB |CERTH is supervising the ERICLL db (https://www.ericll.org/ongoing-projects/) project of ERIC, The European Research Initiative on CLL, Scientific Working Group of the European Haematology Association. This is a large-scale initiative aimed at addressing the outstanding basic, translational and clinical research questions in chronic lymphocytic leukemia (CLL).
INAB |CERTH is also active in the collection, management and analysis of heterogeneous data from patients with other hematological malignancies (e.g. chronic myelogenous leukemia, splenic lymphomas etc.) but also, more frequently, other types of NCDs (e.g. chronic obstructive pulmonary disease). Moreover, it coordinates the IMGT/CLL-DB (https://www.imgt.org/CLLDBInterface/query), a joint academic initiative started by IMGT and ERIC, devoid of any commercial interest, focusing on the molecular epidemiology of lymphoid cancer and currently holding immunogenetic data from >32,000 patients from 23 different Institutions worldwide.

INAB|CERTH engages in pharmacological research, with major emphasis on drug safety and pharmacovigilance, focusing on the following aspects:

• Development of advanced Knowledge Bases for pharmacovigilance by linking multiple data, evidence and knowledge sources.
• Efficient use (and assessing the value of) emerging data sources for “active” post-marketing drug surveillance.
• Development of modern tools to support drug safety experts in systematic safety signal assessment.
• Prevention of adverse drug events in the hospital environment and safer e-prescription.
• Understanding healthcare professionals’ needs for decision support in Computerized Provider Order Entry systems.

In particular, INAB|CERTH develops new mechanisms for active, post-marketing drug safety surveillance. These mechanisms combinedly exploit established data sources for pharmacovigilance, i.e. spontaneous reporting systems, as well as new/emerging data sources, such as Electronic Health Records (EHRs), bibliographic databases and social media platforms [https://www.ncbi.nlm.nih.gov/pubmed/28270198]. ΙΝAΒ|CERTH extends the use of the above methods exploiting big data to additional public health issues, e.g. to identify trends / views of patients expressed in social media about new therapeutic approaches [https://dx.doi.org/10.1007/978-3-319-55014-5_4]. In addition, ΙΝAΒ|CERTH exploits its know-how in the domain of knowledge engineering and linked data for: (a) knowledge discovery regarding drug safety [https://dx.doi.org/10.1007/978-3-319-70284-1_24] and drug repositioning, and (b) the enrichment of public pharmacological data [https://dx.doi.org/10.3389/fphar.2018.00609], to be compliant with FAIR (Findable, Accessible, Interoperable and Reusable [https://dx.doi.org/10.1038/sdata.2016.18]) data principles.
In addition, ΙΝAΒ|CERTH develops clinical decision support systems for safe e-prescription in the clinical environment, integrated in Computerized Provider Order Entry (CPOE) and EHR systems. The integration of decision support functions in the above-mentioned systems has been identified as a major advancement by health professionals. In particular, an international, comparative study involving 1,018 clinicians from 9 countries and 11 hospitals with the participation of INAB|CERTH researchers showed that clinicians’ view on decision support services in e-prescription systems is positive, recognizing significant benefits for patient safety and quality of care regardless of the country, the work environment and the personal experience of those involved in the study with such systems or services [https://dx.doi.org/10.3414/ME12-02-0007/].

The use of mHealth applications, personal health devices, sensors and standardized questionnaires constitutes an important data collection tool for patients and their carers. The “digital patient” is an emerging paradigm engaging patients in self-managing their disease. The goal is to improve various aspects of the patient’s life and health through personalized assessment of response to treatment, disease progression, and behavioural issues utilizing the recorded data, empowering this way the patient as an active participant in his / her disease management. Large-scale “digital patient” applications pose significant challenges related to the management and analysis of a large volume of heterogeneous data.
ΙΝAΒ|CERTH develops patient empowerment systems in close collaboration with patients and their carers [https://doi.org/10.1093/tbm/iby017, https://doi.org/10.1136/bmjopen-2017-016781]. It focuses also on cybersecurity of eHealth systems and services [https://doi.org/10.1016/j.jnca.2018.05.012], with major emphasis on the impact that cybersecurity risks may have for patient safety and interoperability in cross-border health data exchange within EU

The INAB patient empowerment program focuses on chronic non-communicable diseases in order to:

• create effective and structured protocols and tools for doctor-patient communication
• analyze the potential effect of various patient empowerment tools on treatment outcomes
• develop guidance on the approach of patients suffering from chronic non-communicable diseases
• update clinical practice guidelines on chronic non-communicable diseases about ways to improve (self) management of chronically ill patients
• determine the financial implications of such an approach to the health system