Haematopoiesis is required for the daily regeneration of blood and immune cells throughout life. This process is tightly regulated by the multipotent properties of haematopoietic stem cells (HSCs) residing in the bone marrow (BM). During ageing, molecular changes in HSCs often lead to a pre-malignant state for blood cancers termed "clonal haematopoiesis", which is characterised by the presence of HSC clones harbouring certain somatic mutations, primarily in genes involved in epigenetic regulation. Clonal haematopoiesis is prevalent in the ageing population and increases the risk of blood cancers and other comorbidities, such as cardiovascular diseases.
Our research group focuses on understanding the biology of these mutations and how they contribute to the development of leukaemia and other age-related blood diseases. Of major interest is the signalling crosstalk between HSCs, immune cells and the BM microenvironment. Our approach is based on multi-modal studies of human and mouse tissues, applying a combination of genomic profiling, functional assays, screening of epigenetic/metabolic modulators, and murine disease models.
We further established a multi-disciplinary collaboration with pathologists curating a large biobank of human BM biopsies from an aged population to study the immunological and transcriptional changes in clonal haematopoiesis and related leukaemia by combining spatial multiplex confocal imaging, single-cell sequencing analysis and BM organoid co-culture assays.
Our aim is to identify the molecular regulatory processes that are dysregulated during HSC ageing and lead to cancer transformation, immune escape and therapy resistance. Our efforts will contribute to the development of novel therapeutic strategies aimed at improving blood-related diseases and patient care.
- Since 2018: Young Group Leader, DKTK Frankfurt/Mainz, University Medical Center (UMC), Mainz
- 2014 - 2017: Research Associate, Stem Cell & Cancer Research Institute, McMaster University
- 2006 - 2014: Postdoctoral Fellow, Stem Cell & Cancer Research Institute, McMaster University
- 2002 - 2006: PhD, Institute de Biologie Paris-Seine, Sorbonne University Pierre and Marie Curie Campus, Paris
- 1999 - 2002: Master thesis, Institute de Biologie Paris-Seine
Selected publications by Borhane Guezguez
Legscha KJ, Antunes Ferreira E, Chamoun A, Lang A, Awwad MHS, Ton GNHQ, Galetzka D, Guezguez B, Hundemer M, Bourdon JC, Munder M, Theobald M and Echchannaoui H (2021) Δ133p53α enhances metabolic and cellular fitness of TCR-engineered T cells and promotes superior antitumor immunity. J Immunother Cancer, 9:e001846 Link
Woods K and Guezguez B (2021) Dynamic changes of the bone marrow niche: mesenchymal stromal cells and their progeny during aging and leukemia. Frontiers Cell Dev Biol, 9:714716 Link
Guezguez B, Almakadi M, Benoit YD, Shapovalova Z, Rahmig S, Fiebig-Comyn M, Casado FL, Tanasijevic B, Bresolin S, Masetti R, Doble BW and Bhatia M (2016) GSK3 deficiencies in hematopoietic stem cells initiate pre-neoplastic state that is predictive of clinical outcomes of human acute leukaemia. Cancer Cell, 29:61–74 Link
Benoit YD*, Guezguez B*, Boyd AL and Bhatia M (2014) Epigenetic modulation of Wnt/Glycogen synthase kinase-3 signaling to target human cancer stem cells. Clinical Cancer Research, 20:5372–5378 (*indicates joint contribution) Link
Guezguez B, Campbell CJV, Boyd AL, Karanu F, Casado FL, Di Cresce C, Collins TJ, Shapovalova Z, Xenocostas A and Bhatia M (2013) Regional localization within the bone marrow influences the functional capacity of human HSCs. Cell Stem Cell, 13:175–89 Link