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Vincenzo Calvanese's picture

LMCB Junior Group Leader, Wellcome Sir Henry Dale Fellow

v.calvanese@ucl.ac.uk

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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 focuses on 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.
 
 

Selected publications

Calvanese V, et al (2019). MLLT3 governs human haematopoietic stem-cell self-renewal and engraftment. Nature, Dec;576(7786):281-286. doi:10.1038/s41586-019-1790-2. PMID: 31776511
Dou DR, et al (2016). Medial HOXA genes demarcate haematopoietic stem cell fate during human development. Nat Cell Biol , Jun;18(6):595-606. PMCID:PMC4981340.
Calvanese V, et al. (2012). A promoter DNA demethylation landscape of human hematopoietic differentiation. Nucleic Acids Research, Jan 1;40(1):116-131. PMC3245917 
Calvanese V, et al (2010). Sirtuin 1 regulation of developmental genes during differentiation of embryonic stem cells.  Proc Natl Acad Sci USA; Aug 3;107(31):13736-41. PMC2922228. 
 

Funders

Wellcome Trust
Royal Society
 

Research themes

Somatic stem cells
Stemness and differentiation
Epigenetics
Transcriptional regulation
Signaling pathways
Cell-cell interactions
Cellular plasticity
 

Technology

Gene expression
Epigenetic profiling
Flow cytometry
High throughput screening
Transcriptomics
Gene editing
 

Collaborators

Andrew Elefanty, MCRI, Australia
Hanna Mikkola, UCLA Broad Stem Cell Center, USA
Katja Schenke-Leyland, University Women's Hospital Tubingen, Germany