LMCB Junior Group Leader, Wellcome Sir Henry Dale Fellow
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Stem cell self-renewal in haematopoiesis
Research synopsis
Haematopoietic stem cells (HSC) provide a lifelong supply of blood and immune cells. While they continuously produce specialised cells, they also replenish a pool of stem cells in the bone marrow, a property known as self-renewal. Thanks to this property, bone marrow or cord blood transplantation provide a life-saving treatment for blood and immune-related diseases. Unfortunately, donor-matching or insufficient number of cells still render these therapies unfeasible or unsuccessful for certain patients.
Attempts to overcome these limitations have been unable to create or expand in a dish a reliable source of blood stem cells for patients, mostly because of defective self-renewal. Our research focusesÌýon understanding the establishment and maintenance mechanisms that endow human HSC self-renewal, as determined by the expression of specific genes sets that define HSC function. We investigate the regulation of the expression of such HSC-defining genes, how the environment and the metabolism affect this regulation, and how attempts to make or maintain these cells in vitro can be improved to preserve their stemness. By gaining a better understanding of HSC biology, our studies aim to contribute to the development of novel HSC-based therapies.
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Selected publications
Calvanese V, et al (2022). .ÌýNature,Ìý604,Ìý534–540.ÌýPMID: 35418685 ÌýDOI: 10.1038/s41586-022-04571-x
Calvanese V, et al (2019). . Nature, Dec;576(7786):281-286. doi:10.1038/s41586-019-1790-2. PMID: 31776511
Ng ES, et al (2016). . Nature Biotech, Nov;34(11):1168-1179. PMID: 27748754.Ìý
Dou DR, et al (2016). . Nat Cell Biol , Jun;18(6):595-606. PMCID:PMC4981340.
Calvanese V, et al. (2012). . Nucleic Acids Research, Jan 1;40(1):116-131. PMC3245917Ìý
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Funders
WellcomeÌý
Royal Society
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Research themes
Somatic stem cells
Stemness and differentiation
Epigenetics
Transcriptional regulation
Signaling pathways
Cell-cell interactions
Cellular plasticity
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Technology
Gene expression
Epigenetic profiling
Flow cytometry
High throughput screening
Transcriptomics
Gene editing
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People
Chiara Perrod (Postdoctoral associate)
Sazia Rahman (PhD student)
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Collaborators
Andrew Elefanty, MCRI, Australia
Hanna Mikkola, ¹û¶³Ó°ÔºA Broad Stem Cell Center, USA
Katja Schenke-Leyland,ÌýUniversity Women's Hospital Tubingen, Germany
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