Academic Center for Hemoglobinopathies and Rare Anemias

Our mission is to improve diagnosis, prognosis, treatment and clinical care for hemoglobinopathy and rare anemia patients.

Academic Center of Excellence

Research Activities

Our mission is to improve diagnosis, prognosis and clinical care for HERA patients. We will integrate internationally renowned fundamental research (De Pater, Philipsen and Van Dijk), clinical genetics (Harteveld, Joosten and Petrij) and biomarker discovery (Russcher and De Rijke) with two nationally recognized Clinical Expertise Centers for pediatric and adult HERA patients (Cnossen, Rijneveld, Van Lom and Van Ommen) and clinical research on HSCT for HERA patients (Lankester and Smiers).

This ACE will facilitate direct interactions between fundamental, translational and clinical research. We aim to optimize implementation of scientific progress in clinical practice. Vice versa, original clinical observations will be investigated in detail using the most up-to-date developments in molecular biology.

Major research topics:

  1. Improving genotype-phenotype correlations in patients using NGS.
  2. Functional analysis of genetic variants using genome editing in the zebrafish model system.
  3. Reactivation of fetal hemoglobin expression to ameliorate the symptoms of HERA patients: to identify druggable targets for gamma-globin reactivation in adults.
  4. Clinical research including adherence studies (TEAM), observational follow-up of neonatally diagnosed patients (FOCUS), patients with neurovascular complications (FIND), prevention of acute chest syndrome, development of antibodies after blood transfusion (STAR), drug trials e.g. Sevuparin placebo-controlled trial, HSCT for HERA patients (SCORE).

Type of


We combine clinical and fundamental research related to hemoglobinopathies and rare anemias.



We are currently teaching fundamental and clinical aspects of Biomedicine at all academic levels (BSc, MSc, MD, PhD,). This includes lectures (for 10-450 students), self-study assignments, "vaardigheidsonderwijs" (VOs), laboratory practicals (3-5 weeks) and laboratory and clinical research projects (5-9 months).
Topics covered include molecular biology (e.g. transcriptional regulation, epigenetics), the human genome and genetics (e.g. genomic variants, genome engineering, molecular cloning), as well as clinical aspects of hemoglobinopathies and rare anemias. We are also active in post-academic teaching to first and second line medical professionals (PAOG, PAOK, NVK congress and Dutch Hematology Conference, European Hematology Association).

To keep these teaching activities in touch with the very rapid developments in biomedical research and clinical care, we review, update and extend our teaching activities annually, in addition to monitoring by SET Q, D-RECT, visitation and educational audit reports.

Number and origin of the international students and/or residents and/or fellows and PhD students:

Brazil 2;
China 1;
Curacao 1;
Cyprus 2;
Germany 2;
Greece 3;
Iran 2;
Italy 4;
Malta 4;
Nigeria 1;
Spain 3;
Surinam 2;
Turkey 3.


Care Activities

In our nationally recognized Clinical Expertise Centers, which were awarded a five year accreditation, all HERA patients are labelled as tertiary care patients according to various ROBIJN criteria. The clinical departments of (pediatric) hematology and clinical genetics are all audited regularly with regard to quality of patient care, education and innovative research. Care is organized according to value-based health care principles as described by M.E. Porter and co-workers (e.g. Harv Bus Rev. 2011 89:46-52, 54, 56-61)

This multidisciplinary concept was recently implemented successfully by the Erasmus MC team under supervision of Prof. J. Hazelzet after construction in close collaboration with professional caretakers and patients. Outcome measures have been established and ICT support has been implemented to actively monitor these end points. A close collaboration is in place with the National Patient Society (OSCAR) with an ACE member (Cnossen) in the medical board. In addition, another ACE member (Rijneveld) is head of the National Clinical Working Party on Hemoglobinopathhies (LWHB). Research results on adherence, complications of blood transfusion, neurovascular complications and others are implemented in daily care as quickly as possible, with adherence to the health care principles outlined above.

Societal Relevance to Research, Education and Patient Care

To provide the best possible multi-disciplinary, value-based health care for our patients, all suffering from a severe chronic disease with a shortened life expectancy due to multi-organ failure. To prevent disease complications by improvement of adherence to current treatment, early diagnosis of suspect symptoms and periodic screening programs of organ functions in collaboration with various medical specialists.

To inform other health care professionals and the public about the diseases and their manifestations in close collaboration with the patient society OSCAR. To provide expert genetic counselling for carriers of hemoglobinopathies and rare anemias, in order to facilitate reproductive autonomy and to be able to start early therapeutic intervention if indicated. To improve care by initiation and participation in scientific research focusing on innovative therapies such as hematopoietic stem cell transplantation, fetal hemoglobin production and (inter)national drug trials.

To enhance public knowledge of these devastating diseases which are endemic in large parts of the world. To enhance public knowledge on inheritance of these disease by genetic counseling and public campaigns on the impact of these diseases. To ensure best possible treatment of HERA patients in The Netherlands as patients and families are often not able to speak up for themselves.

Viability of Research, Education and Patient Care

By combining fundamental, translational and clinical research the viability of best possible patient care, education and research is enhanced. HERA will provide an attractive framework for funding by charitable and commercial third parties. Such funding opportunities are currently underexplored. Our PhD students will participate in at least 2 international scientific meetings during their PhD. The vast majority of publications is in the international peer-reviewed literature (see question 6).

International work experience is obtained in various ways. Many of our PhD students come from abroad in the first place. Once in Rotterdam, they are exposed to an internationally oriented research environment. Secondments are encouraged by our participation in bi-lateral (Collaborative Research Center TRR81, Germany) and European consortia (fp7 THALAMOSS). We have well-established talent monitoring/review systems in place through participation in the research master Molecular Medicine and the research schools MolMed and MGC.

A bibliometric network analysis of the coordinator reveals that he performs well above the median for the field of hematology (median impact factor 2.46, coordinator average citations per item 39.02). HERA is based on new collaborations crossing the boundaries between fundamental, translational and clinical research, a full bibliometric analysis of HERA as a whole is currently not feasible.

Key and relevant publications of the last five years

  • Sins JW, Biemond BJ, van den Bersselaar SM, Heijboer H, Rijneveld AW, Cnossen MH, Kerkhoffs JH, van Meurs AH, von Ronnen FB, Zalpuri S, de Rijke YB, van der Schoot CE, de Haas M, van der Bom JG, Fijnvandraat K (2016) Early occurrence of red blood cell alloimmunization in patients with sickle cell disease. Am J Hematol DOI 10.1002/ajh.24397
  • Keller CC, Joosten M, Middeldorp AM, Knapen MF (2015) Fetal anemia caused by the Guadalajara variant of G6PD deficiency. Prenat Diagn 35: 1255-1257
  • Schimmel M, van Beers EJ, van Tuijn CF, Nur E, Rijneveld AW, Mac Gillavry MR, Brandjes DP, Schnog JJ, Biemond BJ, Curama study group (2015) N-terminal pro-B-type natriuretic peptide, tricuspid jet flow velocity, and death in adults with sickle cell disease. Am J Hematol 90: E75-76
  • Xiao Y, Zijl S, Wang L, de Groot DC, van Tol MJ, Lankester AC, Borst J (2015) Identification of the Common Origins of Osteoclasts, Macrophages, and Dendritic Cells in Human Hematopoiesis. Stem Cell Reports 4: 984-994
  • Paciaroni K, Lucarelli G, Martelli F, Migliaccio AR, von Lindern M, Borg J, Gillemans N, van Dijk TB, Philipsen S (2014) Transfusion-independent beta(0)-thalassemia after bone marrow transplantation failure: proposed involvement of high parental HbF and an epigenetic mechanism. Am J Blood Res 4: 27-32
  • van Zwieten R, Veldthuis M, Delzenne B, Berghuis J, Groen J, Ait Ichou F, Clifford E, Harteveld CL, Stroobants AK (2014) Hemoglobin analyses in the Netherlands reveal more than 80 different variants including six novel ones. Hemoglobin 38: 1-7
  • de Pater E, Kaimakis P, Vink CS, Yokomizo T, Yamada-Inagawa T, van der Linden R, Kartalaei PS, Camper SA, Speck N, Dzierzak E (2013) Gata2 is required for HSC generation and survival. J Exp Med 210: 2843-2850
  • Esteghamat F, Gillemans N, Bilic I, van den Akker E, Cantu I, van Gent T, Klingmuller U, van Lom K, von Lindern M, Grosveld F, van Dijk T, Busslinger M, Philipsen S (2013) Erythropoiesis and globin switching in compound Klf1::Bcl11a mutant mice. Blood 121: 2553-2562
  • Giardine B, Borg J, Higgs DR, Peterson KR, Philipsen S, Maglott D, Singleton BK, Anstee DJ, Basak AN, Clark B, Costa FC, Faustino P, Fedosyuk H, Felice AE, Francina A, Galanello R, Gallivan MV, Georgitsi M, Gibbons RJ, Giordano PC, Harteveld CL, Hoyer JD, Jarvis M, Joly P, Kanavakis E, Kollia P, Menzel S, Miller W, Moradkhani K, Old J, Papachatzopoulou A, Papadakis MN, Papadopoulos P, Pavlovic S, Perseu L, Radmilovic M, Riemer C, Satta S, Schrijver I, Stojiljkovic M, Thein SL, Traeger-Synodinos J, Tully R, Wada T, Waye JS, Wiemann C, Zukic B, Chui DH, Wajcman H, Hardison RC, Patrinos GP (2011) Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach. Nat Genet 43: 295-301
  • Borg J, Papadopoulos P, Georgitsi M, Gutierrez L, Grech G, Fanis P, Phylactides M, Verkerk AJ, van der Spek PJ, Scerri CA, Cassar W, Galdies R, van Ijcken W, Ozgur Z, Gillemans N, Hou J, Bugeja M, Grosveld FG, von Lindern M, Felice AE, Patrinos GP, Philipsen S (2010) Haploinsufficiency for the erythroid transcription factor KLF1 causes hereditary persistence of fetal hemoglobin. Nat Genet 42: 801-805. Best cited (135x).

PhD theses of the last five years

  • Maria Mikropoulou (Ph.D. awarded 21-06-2016) An shRNA screen for the discovery of suppressors of fetal hemoglobin
  • Ileana Cantù (Ph.D. awarded 04-11-2015) KLF1 in erythroid differentiation
  • Divine Kulu (Ph.D. awarded 09-10-2013) The role of Sp1 and Sp3 transcription factors in hematopoiesis
  • Pavlos Fanis (Ph.D. awarded 20-10-2011) Functional proteomics analysis of transcription factor networks in erythroid cells
  • Sahar Esteghamat (Ph.D. awarded 20-10-2011) Erythropoiesis and hemoglobin regulation: a journey from laboratory to disorders

Non-scientific publications related to the ACE

Principal coordinator(s)

Collaborating investigator(s)

Last updated: 365 days ago.