Dr Miguel Ganuza

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Overview
Team
Research
Key Publications
Major Funding
Other Activities
Biography
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Reader in Haematopoietic Stem Cell Biology

Overview

Our goal is to identify mechanisms that support haematopoietic stem cell function and understand how the leukaemic stem cells “play” with these mechanisms to thrive.

Team

Research

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.

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:

Develop novel niche-based therapies to maintain HSC fitness during ageing (to prevent the emergence of clonal haematopoiesis, BM failure and other conditions)
Successfully target LSCs in leukaemia treatments.
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.

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.

Key Publications

The global clonal complexity of the murine blood system declines throughout life and after serial transplantation. Blood (2019) 133(18):1927-1942. PMID: 30782612

Murine hematopoietic stem cell activity is derived from pre-circulation embryos but not yolk sacs. Nature Communications (2018) 9(1):5405. PMID: 30573729

Life-long hematopoiesis is established by hundreds of precursors throughout mammalian ontogeny. Nature Cell Biology (2017) 19(10):1153-1163. PMID: 28920953

Genetic Inactivation of Cdk7 Leads to Cell Cycle Arrest and Induces Premature Aging Due to Adult Stem Cell Exhaustion. EMBO J (2012) 31(11):2498-510. PMID: 22505032

See recent publications

Major Funding

2022-2024 -The Kay Kendall Leukaemia Fund, £137,792
2021 American Society of Hematology (ASH) Global Research Award, $150,000
2021-2025 – 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
2020-2022 – Leukaemia UK, John Goldman Fellowship, ‘Deconvoluting novel pathways leading to clonal haematopoiesis,’ £123,856
2020-2022 – Barts Charity

Other Activities

Member of the American Society of Hematology (ASH)
Member of the European Hematology Association (EHA)
Member of the International Society of Experimental Hematology (ISEH)
Member of the Spanish Society for Biochemistry and Molecular Biology (SEBBM)

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.

Related News

Miguel Ganuza receives ASH Global Research Award

Congratulations to Dr Miguel Ganuza from Barts Cancer Institute, Queen Mary University of London, who has been selected by the American Society of Hematology (ASH) to receive the 2021 ASH Global Research Award. Dr Ganuza is one of twelve talented early-career investigators selected for this award.

General News 24 August 2021

Understanding the role of the bone marrow in blood cell health and disease

Congratulations to Dr Miguel Ganuza from Barts Cancer Institute’s Centre for Haemato-Oncology who is the recipient of a Career Development Award from the Medical Research Council. The award of approximately £1.5 million over 5 years will fund a research project that will investigate how the bone marrow supports blood stem cells and how changes within the bone marrow can drive the development of diseases, such as leukaemia.

General News 3 December 2020