Developmental biology lab focused on normal and malignant hematopoiesis
We employ synthetic biology to tackle fundamental biological and medical questions.
RESEARCH FOCUS
Our goal is to identify mechanisms that support haematopoietic stem cell function and understand how leukaemic stem cells “play” with these mechanisms to thrive.
Next Generation Technologies
Improving technologies to provide new research approaches.
We have a strong interest in technical innovation and our laboratory is developing novel in vitro and in vivo experimental genetic systems to address critical questions in hematology.
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We aim to provide the research community with novel universally applicable technologies.
Haematopoietic stem cells (HSCs) sit at the top of the haematopoietic hierarchy and replenish all blood cell lineages to support lifelong haematopoiesis. Adult HSCs reside in specialised bone marrow (BM) niches, which support their functions. During leukaemogenesis, HSCs and progenitor cells can acquire mutations that lead to the emergence of leukaemic stem cells (LSCs). LSCs are able to alter the BM niches to thrive. Importantly, quiescent LSCs are resistant to cytotoxic therapies and responsible for leukaemia relapses.
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A clear understanding of the cellular and molecular composition of the BM niches that support and regulate HSC function, and how LSC exploit these niches is fundamental to:
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Develop novel niche-based therapies to maintain HSC fitness during ageing (to prevent the emergence of clonal haematopoiesis, BM failure and other conditions)
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Successfully target LSCs in leukaemia treatments.
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Develop protocols for the efficient in vitro expansion of HSCs for widespread transplantation purposes to improve BM transplantation outcomes, reduce the need of BM donors, model blood conditions and simplify genetic therapy approaches.
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Among the effects of ageing in HSCs, we are interested in unveiling and modelling the mechanisms that drive clonal haematopoiesis (CH, i.e. the expansion of clones harbouring certain mutations that confer them with a particular increase in fitness) and to explore niche-based therapies to prevent it. CH has been recently linked to an increase in the development of leukaemia and cardiovascular conditions.
Our lab combines cutting-edge technologies including state-of-the-art genetic mouse models, multiplex-flow cytometry and single-cell RNA-sequencing to identify and characterise specific bone marrow populations critical to support HSC and LSC functions and to expose mechanisms in CH.
Publications
2022
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Ganuza M*, Hall T, Myers J, Nevitt C, Sánchez-Lanzas R, Chabot A, Ding J, Kooienga E, Caprio C, Finkelstein D, Kang G, Obeng E and McKinney-Freeman S* (2022). Murine fetal liver supports little detectable expansion of life-long hematopoietic progenitors. Nature Cell Biology, Oct 6. doi: 10.1038/s41556-022-00999-5. (*Corresponding authors).
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Sánchez-Lanzas R, Kalampalika F, Ganuza M. ‘Cell-ebrating’ diversity in the bone marrow niche: novel strategies to uncover niche composition (2022). British Journal of Haematology, Jul 15. doi: 10.1111/bjh.18355.
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Ganuza M, Clements W and McKinney-Freeman S (2022). Specification of hematopoietic stem cells in mammalian embryos: A rare or frequent event? Blood, Jul 28;140(4):309-320.
Bogeska R, Mikecin AM, Kaschutnig P, Fawaz M, Büchler-Schäff M, Le D, Ganuza M, Vollmer A, Paffenholz SV, Asada N, Rodriguez-Correa E, Frauhammer F, Buettner F, Ball M, Knoch J, Stäble S, Walter D, Petri A, Carreño-Gonzalez MJ, Wagner V, Brors B, Haas S, Lipka DB, Essers MAG, Weru V, Holland-Letz T, Mallm JP, Rippe K, Krämer S, Schlesner M, McKinney Freeman S, Florian MC, King KY, Frenette PS, Rieger MA, Milsom MD (2022). Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging. Cell Stem Cell, Jul 12:S1934-5909(22)00261-2.
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2020
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Ganuza M, Hall T, Obeng E and McKinney-Freeman S (2020). Clones assemble! The clonal complexity of blood during ontogeny and disease. Experimental Hematology. Jan 29. pii: S0301-472X(20)30030-8.
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2019
Ganuza M, Hall T, Chabot A, Kang G, Finkelstein D and McKinney-Freeman S (2019). The global clonal complexity of the murine blood system declines throughout life and after serial transplantation. Blood, May 2;133(18):1927-1942. Plenary paper. Commented in the same Blood issue (Beerman I. Blood 2019 133:1921-1922).
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2018
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Ganuza M, Chabot A, Tang X, Bi W, Natarajan S, Carter R, Gawad C, Kang G, Chen Y, McKinney-Freeman S (2018). Murine hematopoietic stem cell activity is derived from pre-circulation embryos but not yolk sacs. Nature Communications, Dec 20;9(1):5405.
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Hall T, Walker M, Ganuza M, Holmfeldt P, Bordas M, Kang G, Bi W, Palmer LE, Finkelstein D and McKinney-Freeman S (2018). Nfix promotes hematopoietic stem and progenitor cell survival via regulation of c-Mpl. Stem Cells, Jun;36(6):943-950.
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2017
Ganuza M, Hall T, Finkelstein D, Chabot A, Kang G, McKinney-Freeman S (2017). Life-long hematopoiesis is established by hundreds of precursors throughout mammalian ontogeny. Nature Cell Biology, Oct;19(10):1153-1163.
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Ganuza M, Chabot A, Hadland B, Bernstein I, and McKinney-Freeman S (2017). Hemogenic endothelial precursors display heterogeneous hematopoietic potential ex vivo. Experimental Hematology, July; 51:25-35.
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Ganuza M and McKinney-Freeman S (2017). Hematopoietic stem cells under pressure. Current Opinions in Hematology. July. 24940:314-321.
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2016
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Holmfeldt P*, Ganuza M*, Marathe H, He B, Hall T, Pardieck J, Saulsberry AC, Cico A, Gaut L, McGoldrick D, Finkelstein D, Tan K, McKinney-Freeman S (2016). Functional screen identifies novel regulators of hematopoietic stem cell repopulation. Journal of Experimental Medicine, March 7, 213:3 (*equal contribution). Selected as a “Highlight of the Year” by Journal of Experimental Medicine.
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2012
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Ganuza M, Sáiz-Ladera C, Cañamero M, Gómez G, Schneider R, Blasco M, Pisano D, Paramio JM, Santamaría D and Barbacid M (2012). Genetic Inactivation of Cdk7 Leads to Cell Cycle Arrest and Induces Premature Aging Due to Adult Stem Cell Exhaustion. EMBO J. May 30;31(11):2498-510.
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Ganuza M and Santamaría D (2012). Cdk7: Open questions beyond the prevailing model. Cell Cycle Oct 1;11(19):3519-20.
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MEET THE TEAM
Welcome to the
Ganuza laboratory!
We are committed to excellence in research.
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Miguel Ganuza
Group Leader
Biography
Miguel Ganuza was awarded his PhD from the Universidad Autónoma de Madrid (Spain) in 2009. His dissertation focused on understanding the roles of Cdk7 in cell cycle and transcriptional regulation. He worked as a PhD student in the laboratory of Prof Mariano Barbacid under the guidance of Dr David Santamaría (2004-2011, Spanish National Cancer Center, CNIO, Spain). In 2012 he joined the laboratory of Prof Shannon McKinney-Freeman (2012-2020, St. Jude Children’s Research Hospital, Memphis, USA) to study the molecular processes that govern embryonic haematopoiesis and adult bone marrow transplantation. He joined Barts Cancer Institute in 2020 as a Group Leader..
Raúl Sánchez Lanzas
Postdoctoral Research Associate
Amanda Jiménez Pompa
Postdoctoral Research Associate
Foteini Kalampalika
PhD student
Justin Barclay
Research Technician
NEWS
September 15, 2022
Foteini is awarded the best poster prize during the PhD day at Barts Cancer Institute, Queen Mary University of London.
Congratulations Foteini!
September 1-4, 2022
The lab attends the International Society of Hematology 2022 Annual Meeting in Edinburgh.
July 15, 2022
The lab publishes a Review Article on the cellular composition of the bone marrow niche in the British Journal of Haematology.
We provide a historical perspective on the evolution of techniques used to unveil the cellular components that support hematopoietic stem cells and our view on new tools required to advance the field.
Sánchez-Lanzas R, Kalampalika F, Ganuza M. Br J Haematol. 2022 Jul 15. doi: 10.1111/bjh.18355.
September 26, 2022
Amanda joins the lab as a postdoctoral research associate.
Welcome Amanda!
October 6, 2022
Together with the McKinney-Freeman lab (St. Jude Children's Research Hospital), in our recent article in Nature Cell Biology, we challenge the widely accepted dogma that the haematopoietic stem cell pool expands in the fetal liver.
Our works has important implications into where (which tissue) and when (developmental stage) to search for signals that can be used for the in vitro expansion of blood stem cells for broad bone marrow transplantation purposes. https://www.nature.com/articles/s41556-022-00999-5
OUR FUNDERS
2022-2024 -The Kay Kendall Leukaemia Fund, £137,792.
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2021-2024 - American Society of Hematology (ASH) Global Research Award, $150,000.
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2021-2026 - Medical Research Council, Career Development Award,
'Genetic identification and functional dissection of the bone marrow
niches that support haematopoietic stem cells
and leukaemic stem cells,' £1,528,102
2020-2023 - Leukaemia UK, John Goldman Fellowship,
'Deconvoluting novel pathways leading to clonal haematopoiesis,' £123,856
2020-2024 - Barts Charity
