Professor Constanze Bonifer

Professor Constanze Bonifer

Institute of Cancer and Genomic Sciences
Chair of Experimental Haematology

Contact details

Institute of Cancer and Genomic Sciences
College of Medical and Dental Sciences
University of Birmingham
B15 2TT

Constanze Bonifer is Chair of Experimental Haematology at the Institute of Cancer and Genomic Sciences (ICGS), University of Birmingham, and is Director of the Birmingham Centre of Genome Biology. In their work, they address the question of how the regulators of transcription, the sequence-specific DNA binding proteins or transcription factors, interact with the chromatin template and change its structure. It is known from genetic studies that chromatin modification complexes play essential roles in all phases of the development of multicellular organisms and that transcription factors bring these epigenetic regulatory proteins to specific genes.

One of the great challenges for future biological and medical research will be to understand how all genes and all molecules in a cell work together to generate different cells that each express only one set of genes. To this end, the Bonifer lab employs genome-wide methods such as ChIP-sequencing and DNaseI-sequencing to generate such data. They collaborate with computational biologists to reconstruct models of the molecular interactions driving blood cell development. However, they also study the global consequences of expression of aberrant transcription factors in form of nuclear oncogenes on how the epigenetic landscape is altered in leukaemic cells. The outcome of such studies will shed light on the complex deregulation processes that turn normal into leukaemic cells and will uncover novel therapeutic targets to combat a disease with a high death toll. The results of these experiments are therefore not only important for our understanding of how blood cells form, but are extremely important for how we may diagnose and treat patients in the future.


  • 1995 Habilitation in Molecular Biology and Genetics, University of Freiburg, Germany
  • 1985 PhD in Natural Sciences 1985, University of Heidelberg, Germany



Constanze Bonifer studied Biology at the University of Cologne, Germany and graduated 1980 with a first class degree in Biochemistry, Chemistry and Genetics. She then went on to do a PhD in Biochemistry and Molecular Biology, first at the University of Cologne, then at the Centre for Molecular Biology, University of Heidelberg.

This was followed by Postdoctoral training periods at the Karolinska Institute, Stockholm, and the National Institute for Medical Research in London where she started to work on gene regulation.

1990 she became Assistant Professor and independent group leader at University of Freiburg, Germany, where she worked on gene regulation in the hematopoietic system.

1997 she went back to the UK and became a group leader at the Molecular Medicine Unit, University of Leeds, where she started to work not only on basic mechanisms controlling blood cell development, but also on epigenetic mechanisms controlling leukemogenesis.

She became a Reader in 2000, a Professor in 2003 and in 2004 became a full Professor and Chair of Experimental Haematology. In 2006 she was appointed Head of Section of Expeirmental Haematology at the Leeds Institute of Molecular Medicine.

Since August 2011, Constanze is in Birmingham as Chair of Experimental Haematology at the Institute of Biomedical Research.

Constanze holds a programme grant from Bloodwise, as well as grants from the BBSRC and the Kay Kendall Leukaemia fund, together with several studentships.


Professor Bonifer provides mini-projects and master classes, and gives lectures on haematopoiesis and leukaemia in the MBChB Clinical Sciences haematology module and the Genomic medicine masters programme.

Postgraduate supervision

Constanze has currently five PhD students and is interested in supervising doctoral research in the following areas:

  • Basic mechanisms controlling blood cell development
  • Molecular mechanisms regulating aberrant gene regulation in leukaemia


All blood cells arise from pluripotent stem cells of the bone marrow and develop via different types of precursor cells, which become progressively committed to the different branches of the blood cell system. A number of diseases such as leukaemia affect blood cell development, an understanding of the molecular basis of hematopoietic cell differentiation is therefore of utmost importance for the development of new therapeutic strategies. We want to understand how different genetic programs are activated and silenced at specific stages of haematopoiesis and which factors are involved in this process.

Current research

A large body of evidence from genetic studies demonstrates that genes encoding for chromatin components or chromatin modification complexes play essential roles in all phases of the development of multicellular organisms. At individual genes, these epigenetic regulatory proteins are recruited by sequence-specific transcription factors and influence the transcriptional status and the accessibility to the transcription machinery by altering chromatin structure and the spectrum of biochemical tags attached to individual chromatin components. Such epigenetic events underlay all cell fate decisions and are the basis for the progressive restriction in the developmental potential of all stem cell types. They are also responsible for aberrant cell differentiation in leukaemia. However, very little is known about the molecular details of these processes.

To address the issue of cell specification and cell lineage restriction at the molecular level we study the regulation of chromatin structure of genes expressed in the myeloid lineage of the hematopoietic system. We are identifying the order of events taking place during the developmentally controlled activation of genes and we study how genes are epigenetically silenced. Our research has shown that even before the onset of gene expression and stable transcription factor binding, chromatin of lineage specific genes is partially accessible and transiently bound by transcription factors, and that the silencing of genes during the differentiation of alternative lineages occurs in defined and distinct steps. We have put forward a model of how the balance of transcription factors, chromatin components and chromatin modification complexes lead to the gradual increase and decrease in chromatin accessibility at specific genes during blood cell development. We also have gained a first insight in the epigenetic consequences of the action of nuclear oncoproteins involved in leukaemia. 

To examine the full complexity of regulatory interactions at the genome, we perform research along the following lines:

1)    We study the role of chromatin structure components and specific transcription factors in the activation of genes specific for a given differentiation pathway.

2)    We have developed techniques that are sensitive enough to study the chromatin structure of rare primary precursor cells and we are able to differentiate such cells in vitro.

3)    We are using the differentiation of mouse embryonic stem cells into hematopoietic cells as models to gain insights into early chromatin activation mechanisms and to understand how transcription factors program chromatin. We believe that information of this kind is vital if we want to be able to influence differentiation in a directed fashion.

4)    We are analyzing the impact of mutations in transcription factor and chromatin modifier genes on blood cell development in a system-wide fashion, but to gain mechanistic insights we examine alterations in the chromatin structure of specific target genes.

5)    We have developed high-throughput techniques allowing us to examine the chromatin structure and transcription factor binding site occupancy of extended genomic regions, as regulatory regions of eukaryotic genes can extend over vast regions of DNA and are bound by thousands of transcription factors.

6)    It is now absolutely clear that cancer is an epigenetic disease. A large part of our research that has attracted program grant support is therefore devoted to the question of how the epigenome is reprogrammed in tumour cells. This includes the first description of epigenetic alterations as a function of the expression of a specific leukaemic fusion protein (Follows et al., EMBO J 2003, Ptasinska et al., Cell Reports, 2014) and the first observation of a proto-oncogene being activated by an aberrantly activated repeat element in Hodgkin lymphoma (Lamprecht et al., Nature Medicine, 2010)

7)    Jointly with the lab of Prof Peter Cockerill, we have successfully started to investigate normal and aberrant differentiation processes in a system-wide fashion, using high-throughput sequencing to examine transcription factor occupancy histone modifications (ChIP-seq) and chromatin structure (DNaseI, MNase-seq)

Future plans:

One of the great challenges for future biological research will be to understand in a system-wide fashion how cell fate decisions are regulated. Great progress has been made with respect to identifying individual components of the cell fate decision machinery, such as transcription factors chromatin components and signalling components. However, while recent genome-wide studies allow a first glimpse into the complexities of transcription factor - DNA interactions in specific cell types, we know very little about hierarchical relationships between different network states or how metastable states are established and eventually altered. We do not know how the ordered interplay of transcription factors and specific chromatin states eventually leads to the stable expression of lineage specific genetic programs. We are collaborating with computational biologists to make use of haematopoietic development as particularly powerful system for the reconstruction of dynamic and global models of the molecular interactions governing an entire developmental pathway.

Such information is vital for our translational research program. Interactions between transcription factors and epigenetic regulatory proteins are at the heart of normal and malignant cell differentiation processes and we consider our basic research as a necessary prerequisite to our ongoing efforts to understand and target primary and secondary events in tumour formation at source: in the nucleus of a cell.

Other activities

Constanze Bonifer is the Director of the Birmingham Centre for Genome Biology, a member of the International Society of Experimental Haematology (ISEH) and a member of the Editorial Board of Experimental Hematology.

She was the co-organizer of Cancer Epigenetics conference, May 2013 and the Birmingham Centre for Genome Biology meeting on Genome Biology, 2016. 

Prof Bonifer is a frequent reviewer for international journals (Cell, EMBO J, Genes & Development, J. Experimental Medicine, Nature Genetics, Blood, Stem Cells, Leukemia, Mol. Cell. Biology, J. Biol. Chemistry, PNAS, Human Molecular Genetics, Nucleic Acids Research, Gene, Genome Biology), and also reviews national and international grant proposals and as member of site visit panels. 

Between 2009 and 2012 she was a member of the Bloodwise Career and Fellowship panel, between 2012 and 2014 she was Vice-Chair of Committee C of the BBSRC and she is currently serving for the non-clinical fellowship panel for the MRC.


Constanze Bonifer currently lists 115 publications in PubMed. Here are peer reviewed publications from the last six years:

Lamprecht, B., Walter, K., Kreher, S., Kumar, R., Hummel, M., Lenze, D., Köchert, K., Bouhlel, M.A., Richter, J., Soler, E., Stadhouders, R., Jöhrens, C., Wurster, K.D., Callen, C., Harte, M.F., Giefing, M., Barlow, R., Stein, H., Anagnostopoulos, I., Janz, M., Cockerill, P.N., Siebert, R., Dörken, B., Bonifer, C.*, and Mathas, S.* (2010). (*Joint corresponding authors). De–repression of an endogenous long terminal repeat activates the CSF1R proto–oncogene in human lymphoma. Nature Medicine. 16, 571 - 579

Leddin, M., Perrod, C. , Hoogenkamp, M., Ghani, S., Ass, S., Heinz,S., Wilson, N.K., Follows, G., Schönheit,J., Vockentanz,L., Mosamam,A., Chen, W., Tenen, D.G., Westhead, D.R., Göttgens, B., Bonifer, C*. and Rosenbauer, F*. (2011) (*joint corr. authors). Two distinct auto-regulatory loops operate at the Pu.1 locus in B cells and myeloid cells. Blood. Mar 10;117(10):2827-38

Ingram RM, Valeaux S, Wilson N, Bouhlel MA, Clarke D, Krüger I, Kulu D, Suske G, Philipsen S, Tagoh H, Bonifer C (2011) Differential regulation of sense and antisense promoter activity at the Csf1R locus in B cells by the transcription factor PAX5. Exp Hematol.39(7):730-740

Levantini E, Lee S, Radomska HS, Hetherington CJ, Alberich-Jorda M, Amabile G, Zhang P, Gonzalez DA, Zhang J, Basseres DS, Wilson NK, Koschmieder S, Huang G, Zhang DE, Ebralidze AK, Bonifer C, Okuno Y, Göttgens B, Tenen DG. (2011). RUNX1 regulates the CD34 gene in haematopoietic stem cells by mediating interactions with a distal regulatory element. EMBO J. 30 :4059-4070

Ptasinska, A.; Assi, S.A., James, S.R.,Williamson, D.,Hoogenkamp, M., Mengchu, W., Care, M., McNeill, H., Cullen, M., Tooze, R., Tenen, D.G., Cockerill, P.N. Westhead, D.R.,Heidenreich, O. and Bonifer, C. (2012). Reversible genome-wide epigenetic reprogramming by the leukemia-initiating fusion protein RUNX1/ETO. Leukemia 26:1829-41

Lancrin, C., Mazan, M., Stefanska, M., Lichtinger, M., Costa, G., Vargel, O., Wilson, N., Möröy, T., Bonifer, C., Göttgens, B., Kouskoff, V., and Lacaud, G. (2012) Critical function of GFI1 and GFI1B at the onset of hematopoietic development. Blood 120, 314 – 322

Lichtinger, M., Ingram, R.M., Hannah, R., Clarke, D., Müller, D., Lie-A-Ling, M., Noailles, L., Zhang, P., Wu, M., Tenen, D.G., Assi, S., Westhead, D.R., Kouskoff, V., Lacaud, G., Göttgens, B., and Bonifer, C. (2012) RUNX1 reshapes the epigenetic landscape at the onset of hematopoietic development. EMBO J. 31:4318-33

Baxter EW, Mirabella F, Bowers SR, James SR, Bonavita AM, Bertrand E, Strogantsev R, Hawwari A, Bert AG, Gonzalez de Arce A, West AG, Bonifer C, and Cockerill PN (2012). The inducible tissue-specific expression of the human IL-3/GM-CSF locus is controlled by a complex array of developmentally regulated enhancers. J. Immunol. 189 (9):4459-69

The function of the conserved regulatory element within the first intron of the mammalian Csf1r locus. Sauter, K.A., Bouhlel, M.A., O’Neala, J. 1, Sester, D.P., Tagoh, H. Ingram, R.M., Pridansa, C., Bonifer, C.+, and Hume, D.A. + (2013) (joint corr. Authors). PlosOne.;8(1):e54935

The histone methyltransferase KMT2B is required for RNA polymerase II association and protection from DNA methylation at the MagohB CpG island promoter. Ladopoulos, V., Hofemeister, H., Hoogenkamp, M., Riggs, A.D. Stewart, A.F. and Bonifer, C (2013). Mol Cell Biol. 33(7):1383-1393

Ray, D., Kwon, S.Y., Tagoh, H., Heidenreich, O., Ptasinska, A. and Bonifer, C (2013). Lineage inappropriate PAX5 expression in t(8;21) acute myeloid leukemia requires signalling mediated abrogation of polycomb repression. Blood. 122(5):759-69

Zhang H, Alberich-Jorda M, Amabile G, Yang H, Staber PB, Di Ruscio A, Welner RS, Ebralidze A, Zhang J, Levantini E, Lefebvre V, Valk PJ, Delwel R, Hoogenkamp M, Nerlov C, Cammenga J, Saez B, Scadden DT, Bonifer C, Ye M, Tenen DG. (2013). Sox4 is a key oncogenic target in C/EBPα mutant acute myeloid leukemia. Cancer Cell. 24(5):575-88.

Piper, J., Elze. MC., Cauchy, P., Cockerill, P.N*., Bonifer,C*., Ott, S*. (*joint corr authors) Wellington: A novel method for the accurate identification of digital genomic footprints from DNase-seq data. Nucleic Acids Res. 2013 Nov;41(21):e201.

Gilmour, J., Assi, S.A., Jaegle, U., Kulu, D., van der Werken, H., Clarke, D., Westhead, D.R., Philipsen, S. and Bonifer,C. (2014) A crucial role of the ubiquitously expressed transcription factor Sp1 at early stages of hematopoietic specification. Development. Jun;141(12):2391-401

Lie-A-Ling M, Marinopoulou E, Li Y, Patel R, Stefanska M, Bonifer C, Miller C, Kouskoff V, Lacaud G. RUNX1 positively regulates a cell adhesion and migration program in murine hemogenic endothelium prior to blood emergence. Blood. 2014 Sep 11;124(11):e11-20.

Ptasinska A, Assi SA, Martinez-Soria N, Imperato MR, Piper J, Cauchy P, Pickin A, James SR, Hoogenkamp M, Williamson D, Wu M, Tenen DG, Ott S, Westhead DR, Cockerill PN, Heidenreich O, Bonifer C. Identification of a dynamic core transcriptional network in t(8;21) AML that regulates differentiation block and self-renewal. Cell Reports. 2014 Sep 25;8(6):1974-88.

Kreher S, Bouhlel MA, Cauchy P, Lamprecht B, Li S, Grau M, Hummel F, Köchert K, Anagnostopoulos I, Jöhrens K, Hummel M, Hiscott J, Wenzel SS, Lenz P, Schneider M, Küppers R, Scheidereit C, Giefing M, Siebert R, Rajewsky K, Lenz G, Cockerill PN, Janz M, Dörken B, Bonifer C*, Mathas S* (joint corr. authors). Mapping of transcription factor motifs in active chromatin identifies IRF5 as key regulator in classical Hodgkin lymphoma. Proc Natl Acad Sci U S A. 2014 Oct 21;111(42):E4513-22.

Regha K, Assi SA, Tsoulaki O, Gilmour J, Lacaud G, Bonifer C. (2014) Developmental-stage-dependent transcriptional response to leukaemic oncogene expression. Nature Commun. 2015 May 28;6:7203.

Cauchy P, James SR, Zacarias-Cabeza J, Ptasinska A, Imperato MR, Assi SA, Piper J, Canestraro M, Hoogenkamp M, Raghavan M, Loke J, Akiki S, Clokie SJ, Richards SJ, Westhead DR, Griffiths MJ, Ott S, Bonifer C*, Cockerill PN* (joint corr. Authors). Chronic FLT3-ITD Signaling in Acute Myeloid Leukemia Is Connected to a Specific Chromatin Signature. Cell Rep. 2015 Aug 4;12(5):821-36.

van Oevelen C, Collombet S, Vicent G, Hoogenkamp M, Lepoivre C, Badeaux A, Bussmann L, Sardina JL, Thieffry D, Beato M, Shi Y, Bonifer C, Graf T. C/EBPα Activates Pre-existing and De Novo Macrophage Enhancers during Induced Pre-B Cell Transdifferentiation and Myelopoiesis. Stem Cell Reports. 2015 Aug 11;5(2):232-47.

Susumu Goyama*, Janet Schibler, Anjelika Gasilina, Shan Lin1 Kevin A. Link, Mahesh Shrestha, Jianjun Chen, Susan P. Whitman Clara D. Bloomfield, Salam Assi, Anetta Ptasinska, Olaf Heidenreich, Constanze Bonifer, Nicolas Nassar, James C. Mulloy (2015). UBASH3B (Sts-1)-CBL axis regulates myeloid proliferation in human AML1-ETO-induced leukemia. Leukemia 30, 728 – 739

Jason Piper, Salam A. Assi, Pierre Cauchy, Christophe Ladroue, Peter N. Cockerill*, Constanze Bonifer*, Sascha Ott,* (*Joint corr. Authors). (2015). Wellington-bootstrap: Differential DNase-seq footprinting identifies cell-type determining transcription factors. BMC Genomics. 16; 1000

Bevington SL, Cauchy P, Piper J, Bertrand E, Lalli N, Jarvis RC, Gilding LN, Ott S, Bonifer C, Cockerill PN. (2016). Inducible chromatin priming is associated with the establishment of immunological memory in T cells. EMBO J.;35(5):515-35.

Goode DK, Obier N, Vijayabaskar MS, Lie-A-Ling M, Lilly AJ, Hannah R, Lichtinger M, Batta K, Florkowska M, Patel R, Challinor M, Wallace K, Gilmour J, Assi SA, Cauchy P, Hoogenkamp M, Westhead DR, Lacaud G, Kouskoff V, Göttgens B, Bonifer C. (2016). Dynamic Gene Regulatory Networks Drive Hematopoietic Specification and Differentiation. Dev Cell. 36(5):572-87

Forster VJ, Nahari MH, Martinez-Soria N, Bradburn AK, Ptasinska A, Assi SA, Fordham SE, McNeil H, Bonifer C, Heidenreich O, Allan JM. (2016). The leukemia-associated RUNX1/ETO oncoprotein confers a mutator phenotype. Leukemia. 30(1):251-4.

Illendula, A., Gilmour,J., Grembecka,J., Sesha Srimath Tirumala,V., Boulton, A., Kuntimaddi, A., Schmidt, C., Wang, L., Pullikan, J.A., Zong, H., Parlak, M., Kuscu, C., Pickin, A., Zhou, Y., Gao, Y., Mishra, L., Adli, M., Castilla, L.H., Rajewski, R.A., Janes, K.A., Guzman, M.L., Bonifer, C. and Bushweller, J.H. (2016). Small Molecule Inhibitor of CBFβ-RUNX Binding for RUNX Transcription Factor Driven Cancers. eBiomedicine. Epub May 2016

Bonifer C, Cockerill PN (eds) Transcriptional and Epigenetic Mechanisms Regulating Normal and Aberrant Blood Cell Development. Epigenetics and Human Health, Springer, Heidelberg, 2014. ISBN 978-3-642-45198-0