Professor Simón Méndez-Ferrer
Professor Simón Méndez-Ferrer
Blood stem cell niches
Email: sm2116@cam.ac.uk | Departmental Affiliation: Haematology
Research
Plain English: The Méndez-Ferrer Group's research focuses on the regulation of the environment (‘niche’) in which the blood stem cells reside both in health and disease. Blood stem cells are located in specialised niches which allow them to function according to the organism's requirements. They study the mechanisms of how the stem cell niche fulfils these complex functions. Through this, they aim to understand how the disruption of these mechanisms contributes to blood disorders.
Research Focus: The Méndez-Ferrer laboratory research focuses on the regulation of the haematopoietic stem-cell niche in health and disease. Blood stem cells reside in specialised niches which allows them to self-renew, proliferate, differentiate and migrate according to the organism’s requirements.
The group studies multisystem regulatory mechanisms by which the haematopoietic stem cell niche fulfils these complex functions and how the deregulation of these mechanisms contributes to haematological disorders. A connection was established between the bone marrow, the brain and other systemic signals, which regulate the behaviour of haematopoietic stem cells (HSCs). Additionally, the group has demonstrated that mesenchymal stem cells (MSCs) are very important in supporting and regulating HSCs. This is also the case for malignant HSCs that can cause myeloproliferative disorders, such as myeloproliferative neoplasms (MPNs) and acute myeloid leukaemia (AML).
The group found that malignant HSCs damage their niche to drive disease progression, prompting for strategies targeting the niche, which have been tested in multicentre clinical Phase-II studies. Current group’s efforts focus on the regulation of the HSC niches to improve HSC transplantation procedures and the treatment of myeloproliferative neoplasias.
Main features of anatomically-defined haematopoietic stem cell niches in the mouse bone marrow.
Méndez-Ferrer group photo
Key Publications
Khatib-Massalha E, Di Buduo CA, Chédeville AL, Ho Y-H, Zhu Y, Grockowiak E, Date Y, Khuat LT, Fang Z, Quesada-Salas J, Carrillo-Félez E, Migliavacca M, Montero I, Pérez-Simón JA, Balduini A and Méndez-Ferrer S. Defective neutrophil clearance in JAK2V617F myeloproliferative neoplasms drives myelofibrosis via immune checkpoint CD24. Blood 2025 Aug 7;146(6):717-731. doi: 10.1182/blood.2024027455. PMID: 40373279.
Lisi-Vega LE, Pievani A, García-Fernández M, Forte D, Williams TL, Serafini M and Méndez-Ferrer S. Bone marrow mesenchymal stromal cells support translation in refractory acute myeloid leukemia.Cell Rep 2025 Jan 28;44(1):115151. doi: 10.1016/j.celrep.2024.115151. Epub 2024 Dec 28. PMID: 39932190.
Fang Z, Corbizi Fattori G, ... Méndez-Ferrer S. Tamoxifen for the treatment of myeloproliferative neoplasms: A Phase II clinical trial and exploratory analysis. Nat Commun 2023 Nov 25;14(1):7725. doi: 10.1038/s41467-023-43175-5. PMID: 38001082.
Grockowiak E, Korn C, ... Méndez-Ferrer S. Different niches for mutant stem cells affect pathogenesis and therapy response in myeloproliferative neoplasms. Nat Cancer. 2023 Aug;4(8):1193-1209. doi: 10.1038/s43018-023-00607-x. PMID: 37550517.
- Gadomski S, Fielding C, García-García A, Korn C, Kapeni C, Ashraf S, Villadiego J, del Toro R, Domingues O, Skepper JN, Michel T, Zimmer J, Sendtner R, Dillon S, Poole K, Holdsworth G, Sendtner M, Toledo-Aral JJ, De Bari C, McCaskie AW, Robey RG and Méndez-Ferrer S. A cholinergic neuroskeletal interface promotes bone formation during postnatal growth and exercise. Cell Stem Cell 29, 2022; doi: 10.1016/j.stem.2022.02.008. PMID: 35276096.
- Fielding C, García-García A, Korn C, Gadomski S, Fang Z, Reguera JL, Pérez-Simón JA, Göttgens B and Méndez-Ferrer S. Cholinergic signals preserve haematopoietic stem cell quiescence during regenerative haematopoiesis.Nat Commun. 2022 Jan 27;13(1):543. doi: 10.1038/s41467-022-28175-1. PMID: 35087060.
- Méndez-Ferrer S§, Michurina TV, Ferraro F, Mazloom AR, MacArthur BD, Lira SA, Scadden DT, Ma’ayan A, Enikolopov GN and Frenette PS§. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche.Nature 2010;466:829-834 (§corresponding authors). PMID: 20703299
- Forte D, García-Fernández M, Sánchez-Aguilera A, Stavropoulou V, Fielding C, Martín-Pérez D, López JA, Costa ASH, Tronci L, Nikitopoulou E, Barber M, Gallipoli P, Marando L, Fernández de Castillejo CL, Tzankov A, Dietmann S, Cavo M, Catani L, Curti A, Vázquez J, Frezza C, Huntly BJ, Schwaller J and Méndez-Ferrer S. Bone marrow mesenchymal stem cells support acute myeloid leukemia bioenergetics and enhance antioxidant defense and escape from chemotherapy. Cell Metabolism. 2020 Sep 16:S1550-4131(20)30479-4. doi:10.1016/j.cmet.2020.09.001 PMID: 32966766
- Ho YH, Del Toro R, Rivera-Torres J, Rak J, Korn C, García-García A, Macías D, González-Gómez C, Del Monte A, Wittner M, Waller AK, Foster HR, López-Otín C, Johnson RS, Nerlov C, Ghevaert C, Vainchenker W, Louache F, Andrés V and Méndez-Ferrer S. Remodelling of bone marrow hematopoietic stem cell niches promotes myeloid cell expansion during premature or physiological aging. Cell Stem Cell 2019 Sep 5;25(3):407-418.e6. doi:10.1016/j.stem.2019.06.007. PMID: 31303548
- García-García A, Korn C, García-Fernández M, Domingues O, Villadiego J, Martín-Pérez D, Isern J, Bejarano-García JA, Zimmer J, Pérez-Simón JA, Toledo-Aral JJ, Michel T, Airaksinen MS, Méndez-Ferrer S. Dual cholinergic signals regulate daily migration of hematopoietic stem cells and leukocytes. Blood. 2019 Jan 17;133(3):224-236. doi: 10.1182/blood-2018-08-867648. PMID: 30361261
- Sánchez-Aguilera A, Arranz L, Martín-Pérez D, García-García A, Stavropoulou V, Kubovcakova L, Isern J, Martín-Salamanca S, Langa X, Skoda RC, Schwaller J, Méndez-Ferrer S. Estrogen signaling selectively induces apoptosis of hematopoietic progenitors and myeloid neoplasms without harming steady-state hematopoiesis. Cell Stem Cell 15: 791-780, 2014. PMID:25479752
- Arranz L, Sánchez-Aguilera A, Martín-Pérez D, Isern J, Langa X, Tzankov A, Lundberg P, Muntión S, Tzeng Y-S, Lai D-M, Schwaller J, Skoda RC, Méndez-Ferrer S. Neuropathy of haematopoietic stem cell niche is essential for myeloproliferative neoplasms. Nature 512: 78-81, 2014. PMID:25043017