ANASTASIA CHATZIDIMITRIOU

The research group that I coordinate since 2014 at INAB/CERTH has developed and is active with international recognition in the following research areas and applications:

Basic Research | Immunobiology of lymphoid malignancies

• Characterization of interactions with the microenvironment in mature B cell malignancies through a combined molecular and cellular biology approach
• Immunogenetic analysis in lymphomas and pre-lymphoma states, bone marrow failure syndromes, chronic graft-versus-host disease, infections, autoimmune diseases
• Innovative cellular therapies for the treatment of opportunistic infections and Graft versus Host Disease in patients undergoing allogeneic hematopoietic cell transplantation

Translational Research | Precision Oncology

• Analysis of hematological malignancies to detect new predictive biomarkers and therapeutic targets
• Validation of predictive biomarkers
• Functional confirmation of findings from omic studies
• Integration of clinical and biological data and development of predictive models in order to better stratify cancer patients
• Study of the effects of targeted drugs on the tumor microenvironment in patients with hematological malignancies

Clinical Research

• Observational studies on the treatment and outcome of patients with chronic hematological malignancies (chronic lymphocytic leukemia, chronic myeloid leukemia, lymphomas)
• Post-approval studies for the production of indications from daily clinical practice (real-world evidence) in the context of academic research initiatives and collaborations with industry

Applications

• Diagnostics: Accredited molecular diagnostic services (mainly with NGS methodologies) in patients with cancer and viral infections
• Development of new laboratory protocols and bioinformatics tools in immunogenetics
• Certification of laboratories in the field of lymphoid malignancies
• Development of clinical biological data management systems

A) Contribution to the Molecular Classification of Lymphomas

The results of my scientific and diagnostic work in lymphoid malignancies are widely recognized and included in the key references of the World Health Organization Classification and International Guidelines:

• Swerdlow, S.H., Campo, E., Pileri, S.A., Lee Harris, N., Stein, H., Siebert, R., Advani, R., Ghielmini, M., Salles, G.A., Zelenetz, A.D., Jaffe, E.S.
  The 2016 revision of the World Health Organization classification of lymphoid neoplasms (2016) Blood, 127 (20), pp. 2375-2390 | DOI: 10.1182/blood-2016-01-643569
• Hallek, M., Cheson, B.D., Catovsky, D., Caligaris-Cappio, F., Dighiero, G., Döhner, H., Hillmen, P., Keating, M., Montserrat, E., Chiorazzi, N., Stilgenbauer, S., Rai, K.R., Byrd, J.C., Eichhorst, B., O’Brien, S., Robak, T., Seymour, J.F., Kipps, T.J.
  iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL
  (2018) Blood, 131 (25), pp. 2745-2760 | DOI: 10.1182/blood-2017-09-806398
• Eichhorst, B., Robak, T., Montserrat, E., Ghia, P., Hillmen, P., Hallek, M., Buske, C.
  Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
  (2015) Annals of Oncology, 26, pp. vi50-vi54. | DOI: 10.1093/annonc/mdv303
• Giudicelli, V., Brochet, X., Lefranc, M.-P.
  IMGT/V-QUEST: IMGT standardized analysis of the immunoglobulin (IG) and T cell receptor (TR) nucleotide sequences
  (2011) Cold Spring Harbor Protocols, 6 (6), pp. 695-715.

My specific articles referenced are as follows:

• DOI: 10.1182/blood.2020005216
• DOI: 10.1182/blood.2020007039
• DOI: 10.1158/1078-0432.CCR-15-1170
• DOI: 10.1038/leu.2014.196
• DOI: 10.1016/S2352-3026(14)00005-2
• DOI: 10.1158/0008-5472.CAN-12-1615
• DOI: 10.1182/blood-2011-11-393694
• DOI: 10.1182/blood-2011-03-343434
• DOI: 10.1182/blood-2006-03-012948

Β) PARTNER NETWORK (indicative list)

1. Scientific Societies
   
   • Hellenic Hematology Society | Scientific Collaboration, Clinical Studies, Diagnostic Services, Data Management Systems for Real World Evidence
   • European Hematology Association | Scientific Collaboration, Clinical Studies, Diagnostic Services, Data Management Systems for Real World Evidence
2. Industry
   

   Pharma Industry | Scientific Collaboration, Clinical Studies, Diagnostic Services, Data Management Systems for Real World Evidence, Funding

   1. Janssen Cilag
   2. Gilead Sciences
   3. Abbvie Pharmaceuticals
   4. Abbvie Inc
   5. Novartis Hellas
   6. Roche
   7. Astrazeneca

   Biotechnology Companies | Scientific Collaboration, Products Development

   1. Illumina
   2. ThermoFisher Scientific
   3. SafeBlood-Bioanalytica SA
   4. ANTISEL SA
   5. Zafiropoulos SA
   6. Varelas SA

Α) Diagnostics Experience

• 2003 - 2006 | Lab of Molecular Biology, General Hospital G.Papanikolaou Hematology Clinic and Unit of Transplantation of Hematopoietic Cells, Thesssaloniki
• 2016 - today | Founder and Head of the Unit of the Molecular Diagnostics Unit at INAB/CERTH

1. Biosafety Level 3, BSL-3
2. ISO15189 and UKAS certification for the molecular analysis of biomarkers including next generation sequencing (NGS)
3. Responsible for the Biobank at INAB/CERTH, a Greek Node of the Biobanking and Biomolecular Resources Research Infrastructure – European Research Infrastructure Consortium [BBMRI-ERIC]
4. The Molecular Diagnostics Unit operates as a Reference Laboratory of the European Society of Hematology for lymphoid malignancies (certification of > 150 laboratories) and as a member of the European Euroclonality-NGS Network for the development of protocols and the standardization of antigen receptor analysis with next generation sequencing (NGS methodology) and its applications in hematology, oncology and immunology. Agathangelidis, A. Chatzidimitriou, T. Chatzikonstantinou, C. Tresoldi , Z. Davis, V. Giudicelli, S. Kossida, C. Belessi, R. Rosenquist, P. Ghia, A. W. Langerak, F. Davi, K. Stamatopoulos and on behalf of ERIC, the European Research Initiative on CLL
   Immunoglobulin gene sequence analysis in chronic lymphocytic leukemia: the 2022 update of the recommendations by ERIC, the European Research Initiative onCLL. Leukemia (2022) 36:1961–1968
5. Oncology and Infectious diseases (HPV, SARS CoV-2 viruses): the following accredited molecular tests are carried out:
   • Determination of gene mutations in hematological malignancies and solid tumors | targeted NGS
   • Determination of hereditary cardiovascular disease gene variants | targeted NGS
   • Molecular detection of the HPV virus in the population of Greece (11,000 women) in the context of a study evaluating the self-sampling methodology of cervical material - "Greco self" screening program for cervical cancer | The GRECOSELF Study. Cancer Prev Res (Phila). 2019 Oct;12(10):701-710. doi: 10.1158/1940-6207.CAPR-19-0192
   • Studies of the repertoire of gene rearrangements of the B cell receptor (BcR) in the context of international clinical trials
   • Studies of the repertoire of gene rearrangements of the T cell receptor (TcR) in the context of international clinical trials
   • Molecular detection of the SARS-CoV-2 virus in collaboration with the National Public Health Organization (EODY)
   • Analysis of the SARS-CoV-2 virus genome to detect virus variants - Reference Laboratory for N. Greece

Β) Management Systems for Real World Data

• 2012 - today | Design and supervision of the development of data collection and integration systems for real world data with built-in validation mechanisms to control data quality based on individual needs and different usage scenarios A. Chatzidimitriou, E. Minga, T. Chatzikonstantinou, C. Moreno, K. Stamatopoulos, P. Ghia; on behalf of ERIC, the European Research Initiative on CLL
  Challenges and Solutions for Collecting and Analyzing Real World Data: The Eric CLL Database as an Illustrative Example
  HemaSphere: October 2020, Volume 4, Issue 5 – p e425
• 2017 - today | Collaboration with the Pharmaceutical Industry to conduct post-approval studies from daily clinical practice (Novartis, Jannsen Cilag, Abbvie Inc)
• 2018 - today | Collaboration with the Hellenic Hematology Society and the European Hematology Association for multicenter studies

C] Students Supervision

5 PhD students | 6 MsC theses | 4 Post-doc Researchers

D] Teaching Experience

Undergraduate studies

• 2007 - 2011 | Assistant professor fixed term | Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupoli | Molecular Biology, Human Genetics, Genetics I & II
• 03/2005 - 02/2010 | Assistant professor fixed term | International Hellenic University, Faculty of Technology of Agriculture, Thessaloniki | Genetics

Postgraduate studies

• 2021 & 2022 | Lecturer at the Master's Degree Program "TRANSLATIONAL RESEARCH IN BIOMEDICINE
• Molecular Diagnostics, Biomarkers and Targeted Therapies"| Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupoli

ORCID: 0000-0002-8106-1846

Indicative list of important research publications

1. Gemenetzi K, Psomopoulos F, Carriles AA, Gounari M, Minici C, Plevova K, Sutton LA, Tsagiopoulou M, Baliakas P, Pasentsis K, Anagnostopoulos A, Sandaltzopoulos R, Rosenquist R, Davi F, Pospisilova S, Ghia P, Stamatopoulos K, Degano M, Chatzidimitriou A. Higher-order immunoglobulin repertoire restrictions in CLL: the illustrative case of stereotyped subsets 2 and 169. Blood. 2021 Apr 8;137(14):1895-1904. PMID: 33036024.
2. Agathangelidis A, Galigalidou C, Scarfò L, Moysiadis T, Rovida A, Gounari M, Psomopoulos F, Ranghetti P, Galanis A, Davi F, Stamatopoulos K, Chatzidimitriou A, Ghia P. Infrequent "chronic lymphocytic leukemia-specific" immunoglobulin stereotypes in aged individuals with or without low-count monoclonal B-cell lymphocytosis. Haematologica. 2021 Apr 1;106(4):1178-1181. PMID: 32586905.
3. Agathangelidis A, Chatzidimitriou A, Gemenetzi K, Giudicelli V, Karypidou M, Plevova K, Davis Z, Yan XJ, Jeromin S, Schneider C, Pedersen LB, Tschumper RC, Sutton LA, Baliakas P, Scarfò L, van Gastel EJ, Armand M, Tausch E, Biderman B, Baer C, Bagnara D, Navarro A, Langlois de Septenville A, Guido V, Mitterbauer- Hohendanner G, Dimovski A, Brieghel C, Lawless S, Meggendorfer M, Brazdilova K, Ritgen M, Facco M, Tresoldi C, Visentin A, Patriarca A, Catherwood M, Bonello L, Sudarikov A, Vanura K, Roumelioti M, Skuhrova Francova H, Moysiadis T, Veronese S, Giannopoulos K, Mansouri L, Karan-Djurasevic T, Sandaltzopoulos R, Bödör C, Fais F, Kater A, Panovska I, Rossi D, Alshemmari S, Panagiotidis P, Costeas P, Espinet B, Antic D, Foroni L, Montillo M, Trentin L, Stavroyianni N, Gaidano G, Francia di Celle P, Niemann C, Campo E, Anagnostopoulos A, Pott C, Fischer K, Hallek M, Oscier D, Stilgenbauer S, Haferlach C, Jelinek D, Chiorazzi N, Pospisilova S, Lefranc MP, Kossida S, Langerak AW, Belessi C, Davi F, Rosenquist R, Ghia P, Stamatopoulos K. Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL. Blood. 2021 Mar 11;137(10):1365-1376. PMID: 32992344.
4. Vardi, A, Vlachonikola E, Karypidou M, Stalika E, Bikos V, Gemenetzi K, Maramis C, Siorenta A, Anagnostopoulos A, Pospisilova S, Maglaveras N, Chouvarda I, Stamatopoulos K, Hadzidimitriou A. Restrictions in the T-cell repertoire of chronic lymphocytic leukemia: high-throughput immunoprofiling supports selection by shared antigenic elements. Leukemia. 2017 Jul; 31(7): 1555-1561. PMID: 27904140.
5. Sutton LA, Hadzidimitriou A, Baliakas P, Agathangelidis A, Langerak AW, Stilgenbauer S, Pospisilova S, Davis Z, Forconi F, Davi F, Ghia P, Rosenquist R, Stamatopoulos K; European Research Initiative on CLL (ERIC). Immunoglobulin genes in chronic lymphocytic leukemia: key to understanding the disease and improving risk stratification. Haematologica. 2017 Jun;102(6):968-971. PMID: 28566340.
6. Rosenquist R, Ghia P, Hadzidimitriou A, Sutton L-A, Agathangelidis A, Baliakas P, Darzentas N, Giudicelli V, Lefranc M-P, Langerak AW , Belessi C, Davi F , Stamatopoulos K. Immunoglobulin gene sequence analysis in chronic lymphocytic leukemia: updated ERIC recommendations. Leukemia. 2017 JUL;31(7):1477-1481. PMID: 28439111.
7. Bikos V, Karypidou M, Stalika E, Baliakas P, Xochelli A, Sutton LA, Papadopoulos G, Agathangelidis A, Papadopoulou E, Davis Z, Algara P, Kanellis G, Traverse-Glehen A, Mollejo M, Anagnostopoulos A, Ponzoni M, Gonzalez D, Pospisilova S, Matutes E, Piris MA, Papadaki T, Ghia P, Rosenquist R, Oscier D, Darzentas N, Tzovaras D, Belessi C, Hadzidimitriou A, Stamatopoulos K. An Immunogenetic Signature of Ongoing Antigen Interactions in Splenic Marginal Zone Lymphoma Expressing IGHV1-2*04 Receptors. Clin Cancer Res. 2016 Apr 15;22(8):2032-40. PMID: 26647217.
8. Vardi A, Agathangelidis A, Stalika E, Karypidou M, Siorenta A, Anagnostopoulos A, Rosenquist R, Hadzidimitriou A, Ghia P, Sutton LA, Stamatopoulos K. Antigen Selection Shapes the T-cell Repertoire in Chronic Lymphocytic Leukemia. Clin Cancer Res. 2016 Jan 1;22(1):167-74. PMID: 26338994.
9. Baliakas P, Hadzidimitriou A, Agathangelidis A, Rossi D, Sutton LA, Kminkova J, Scarfo L, Pospisilova S, Gaidano G, Stamatopoulos K, Ghia P, Rosenquist R. Prognostic relevance of MYD88 mutations in CLL: the jury is still out. Blood. 2015 Aug 20;126(8):1043-4. PMID: 26294719.
10. Hadzidimitriou A, Stamatopoulos K, Belessi C, Lalayianni C, Stavroyianni N, Smilevska T, Hatzi K, Laoutaris N, Anagnostopoulos A, Kollia P, Fassas A. Immunoglobulin genes in multiple myeloma: expressed and non-expressed repertoires, heavy and light chain pairings and somatic mutation patterns in a series of 101 cases. Haematologica. 2006 Jun;91(6):781-7. PMID: 16769580.