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.
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
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:
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.
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.