Katrin Ottersbach
Professor of Developmental Haematology / Cancer Research UK Fellow

- Centre for Regenerative Medicine
Contact details
- Tel: +44 (0)131 651 9500
- Email: katrin.ottersbach@ed.ac.uk
Address
- Street
-
Centre for Regenerative Medicine
Institute for Regeneration and Repair
The University of Edinburgh
Edinburgh BioQuarter
5 Little France Drive - City
- Edinburgh
- Post code
- EH16 4UU
Background
2015 - Current: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK - Principal Investigator
2012 - 2015: Wellcome Trust – MRC Cambridge Stem Cell Institute, Cambridge, UK - Principal Investigator
2006 - 2015: Department of Haematology, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, UK - Principal Investigator
2001 - 2006: Group of Prof. Elaine Dzierzak, Erasmus MC, Rotterdam, The Netherlands - Postdoctoral Fellow
Qualifications
1997 - 2001: CRC Beatson Institute for Cancer Research, Glasgow, UK - PhD: MIP-1a: A Structure-Function Study, supervisor Prof. Gerard Graham
1993 - 1997: University of Edinburgh, Edinburgh, UK - BSc with Honours in Biochemistry: First Class
Open to PhD supervision enquiries?
Yes
Current PhD students supervised
Eric Antunes
Alasdair Duguid
Leslie Nitsche
Past PhD students supervised
Vasiliki Symeonidou
Nada Zaidan
Chrysa Kapeni
Wendi Bacon
Neil Barrett
Maria Mascarenhas
Bahar Mirshekar-Syahkal
Research summary
Developmental origins of blood stem cells and leukaemia
Blood stem cells have the ability to produce every blood cell type and are therefore of immense clinical importance. Our group investigates how these cells are first generated during foetal development, how they can be maintained and what their unique properties are. A further interest of our group is how these early blood cells are targeted by mutations that can lead to cancer development in infant patients.
Aims and areas of interest
One major part of my group's research is to understand how the first haematopoietic stem cells (HSCs) are generated during development and how their subsequent expansion, migration and differentiation are regulated. A particular focus in this context is the identification of the cellular and molecular composition of the microenvironment that facilitates the emergence of HSCs and how this composition changes as HSCs mature and migrate in the developing foetus. The ultimate aim is to dissect out the specific components required for particular HSC functions so that the right conditions can be recreated to achieve HSC generation, expansion and differentiation in vitro. We have recently demonstrated that the transcription factor Gata3 via its role in the sympathetic nervous system is required for HSC production, thus functionally linking these two co-developing systems. We are continuing our studies on how exactly catecholamines, the mediators of the sympathetic nervous system, act on emerging HSCs. We also have evidence that Gata3 performs additional functions during HSC emergence which we are currently investigating.
Embryonic and foetal haematopoietic cells have unique properties with respect to proliferation response and differentiation bias. These are important in the context of HSC expansion and certain types of infant leukaemia that have a prenatal origin, and are another area of interest in the lab. We are particularly interested in infant leukaemias that have chromosomal rearrangements at the MLL locus as these have a particularly poor prognosis. Using MLL-AF4 and MLL-AF9 as examples, our aim is to characterise the foetal-specific context that contributes to disease development and how these oncofusions compromise normal blood development. The overall aim is to identify more specific therapeutic targets and to develop faithful in vivo models in which these can be tested.
Affiliated research centres
Current project grants
Cancer Research UK Programme Foundation Award
Kay Kendall Leukaemia Fund project grant
Blood Cancer UK project grant
Past project grants
LLR Bennett Senior Fellowship
Kay Kendall Leukaemia Fund Intermediate Fellowship
British Society of Haematology Early Stage Investigator Fellowship
University of Edinburgh Chancellor's Fellowship
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p57Kip2 regulates embryonic blood stem cells by controlling sympathoadrenal progenitor expansion
In:
Blood, vol. 140, pp. 464-477
DOI: https://doi.org/10.1182/blood.2021014853
Research output: Contribution to Journal › Article (Published) -
Endothelial-specific Gata3 expression is required for hematopoietic stem cell generation
In:
Stem Cell Reports
DOI: https://doi.org/10.1016/j.stemcr.2022.06.008
Research output: Contribution to Journal › Article (Published) -
Infant leukaemia – faithful models, cell of origin, and the niche
In:
Disease Models and Mechanisms, vol. 14
DOI: https://doi.org/10.1242/dmm.049189
Research output: Contribution to Journal › Article (Published) -
Defining the fetal origin of MLL-AF4 infant leukemia highlights specific fatty acid requirements.
In:
Cell Reports, vol. 37
DOI: https://doi.org/10.1016/j.celrep.2021.109900
Research output: Contribution to Journal › Article (Published) -
MiR-130b and miR-128a are essential lineage-specific co-drivers of t(4;11) MLL-AF4 acute leukemia
In:
Blood
DOI: https://doi.org/10.1182/blood.2020006610
Research output: Contribution to Journal › Article (Published) -
Single cell analyses and machine learning define hematopoietic progenitor and HSC-like cells derived from human PSCs
(12 pages)
In:
Blood, vol. 136, pp. 2893–2904
DOI: https://doi.org/10.1182/blood.2020006229
Research output: Contribution to Journal › Article (Published) -
HOXA9/IRX1 expression pattern defines two sub-groups of infant MLL-AF4-driven Acute Lymphoblastic Leukemia
In:
Experimental Hematology
DOI: https://doi.org/10.1016/j.exphem.2020.10.002
Research output: Contribution to Journal › Article (Published) -
The MLL/SET family and haematopoiesis
In:
BBA - Gene Regulatory Mechanisms
DOI: https://doi.org/10.1016/j.bbagrm.2020.194579
Research output: Contribution to Journal › Review article (E-pub ahead of print) -
Gata3 targets Runx1 in the embryonic haematopoietic stem cell niche
In:
Iubmb life
DOI: https://doi.org/10.1002/iub.2184
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Fetal liver Mll-AF4+ hematopoietic stem and progenitor cells respond directly to poly(I:C), but not to a single maternal immune activation
In:
Experimental Hematology, vol. 76, pp. 49-59
DOI: https://doi.org/10.1016/j.exphem.2019.07.004
Research output: Contribution to Journal › Article (Published) -
Endothelial-to-haematopoietic transition: an update on the process of making blood
(11 pages)
In:
Biochemical Society Transactions, vol. 47, pp. 591-601
DOI: https://doi.org/10.1042/BST20180320
Research output: Contribution to Journal › Review article (Published) -
DNA damage signalling from the placenta to foetal blood as a potential mechanism for childhood leukaemia initiation
(17 pages)
In:
Scientific Reports, vol. 9
DOI: https://doi.org/10.1038/s41598-019-39552-0
Research output: Contribution to Journal › Article (Published) -
The Multi-faceted role of GATA3 in developmental haematopoiesis
In:
Open Biology
DOI: https://doi.org/10.1098/rsob.180152
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Hematopoietic stem cell transplantation alters susceptibility to pulmonary hypertension in Bmpr2-deficient mice
In:
Pulmonary circulation, vol. 8, pp. 2045894018801642
DOI: https://doi.org/10.1177/2045894018801642
Research output: Contribution to Journal › Article (Published) -
The “Never-Ending” Mouse Models for MLL-Rearranged Acute Leukemia Are Still Teaching Us
In:
HemaSphere, pp. 1
DOI: https://doi.org/10.1097/HS9.0000000000000057
Research output: Contribution to Journal › Editorial (Published) -
The fetal liver lymphoid-primed multipotent progenitor provides the prerequisites for the initiation of t(4;11) MLL-AF4 infant leukemia
In:
Haematologica
DOI: https://doi.org/10.3324/haematol.2018.191718
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Molecular processes involved in B cell acute lymphoblastic leukaemia
(30 pages)
In:
Cellular and Molecular Life Sciences
DOI: https://doi.org/10.1007/s00018-017-2620-z
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Mll-AF4 Confers Enhanced Self-Renewal and Lymphoid Potential during a Restricted Window in Development
In:
Cell Reports, vol. 16, pp. 1039-1054
DOI: https://doi.org/10.1016/j.celrep.2016.06.046
Research output: Contribution to Journal › Article (Published) -
Analysis of Jak2 signaling reveals resistance of mouse embryonic hematopoietic stem cells to myeloproliferative disease mutation
In:
Blood
DOI: https://doi.org/10.1182/blood-2015-08-664631
Research output: Contribution to Journal › Article (Published) -
SMAD1 and SMAD5 Expression Is Coordinately Regulated by FLI1 and GATA2 during Endothelial Development
In:
Molecular and Cellular Biology, vol. 35, pp. 2165-2172
DOI: https://doi.org/10.1128/MCB.00239-15
Research output: Contribution to Journal › Article (Published)
Organiser
Annual Molecular Haemopoiesis meeting
- Cancer Research UK
- Blood Cancer UK (formerly LLR; Bloodwise)
- Kay Kendall Leukaemia Fund
- Prof. Juerg Schwaller, University Hospital Basel, Switzerland
- Prof. Bertie Göttgens, University of Cambridge, UK
- Dr. Chris Halsey, University of Glasgow, UK
- Dr. Kristina Kirschner, University of Glasgow, UK
- Prof. Rose Zamoyska, University of Edinburgh, UK
- Dr Karen Keeshan, University of Glasgow, UK
- Prof. Pablo Menendez, University of Barcelona, Spain
- Prof. Thomas Milne, University of Oxford, UK