Our research aims to understand the biology of leukaemia stem cells and identify the mechanisms they use to escape treatments.
Targeting the RNA m6A Reader YTHDF2 Selectively Compromises Cancer Stem Cells in Acute Myeloid Leukemia. Cell Stem Cell (2019) S1934-5909(19)30120-1. PMID: 31031138
Fumarate hydratase (Fh1) is a critical metabolic regulator of haematopoietic stem cell functions. J Exp Med (2017) 214(3), 719-735. PMID: 28202494
Hif-1α and Hif-2α synergise to suppress AML development but are dispensable for disease maintenance. J Exp Med (2015) 212, 2223-2234. PMID: 26642852
Cited2 is an essential regulator of adult hematopoietic stem cells. Cell Stem Cell (2009) 5, 659-665. PMID: 19951693
Functional epistasis on a common MHC haplotype associated with multiple sclerosis. Nature (2006) 443, 574-577. PMID: 17006452
Cancer stem cells (CSCs) form a distinct population of tumour cells that self-renew and drive cancer formation. Because CSCs are difficult to eradicate using currently available treatment regimens they are responsible for therapeutic resistance in cancer patients. It is therefore of paramount importance to understand how CSCs are generated, why they are treatment-resistant and what pathways they use to self-renew and fuel the disease. Our aim is to address these fundamental questions to provide novel therapeutic targets for CSC eradication.
Our laboratory employs multidisciplinary approaches to understand how HSCs chose to self-renew or differentiate and how these cell fate decisions are affected under pathological conditions to generate leukaemic stem cells. This knowledge is central to clinical applicability of stem cells and will be harnessed to achieve stem cell expansion for transplantation purposes and leukaemic stem cell eradication.
While HSCs reside in the hypoxic (low in oxygen) bone marrow microenvironment, the impact of hypoxia and hypoxia signalling pathways on normal HSC/progenitor fate decisions and leukaemogenesis remains largely unexplored. Our laboratory investigates the impact of hypoxia signalling pathways on HSC functions and addresses how these pathways are subverted to generate leukaemic stem cells. We hope to not only discover therapeutically targetable intrinsic characteristics of leukaemic stem cells, but also use leukaemic stem cells as a model to explore important mechanisms operating in other cancer stem cells.
The mRNA m6A reader YTHDF2 supresses pro-inflammatory pathways and sustains hematopoietic stem cell function Mapperley C, Van De Lagemaat L, Lawson H et al. Journal of Experimental Medicine 218(1) 20200829-20200829
Hypoxia-inducible factor 1 (HIF-1) is a new therapeutic target in JAK2V617F-positive myeloproliferative neoplasms Baumeister J, Chatain N, Hubrich A et al. Leukemia (2020) 34(7) 1062-1074
Divide and Rule: Mitochondrial Fission Regulates Quiescence in Hematopoietic Stem Cells Luis TC, Lawson H, Kranc KR Cell Stem Cell (2020) 26(7) 299-301
Systemic silencing of Phd2 causes reversible immune regulatory dysfunction Yamamoto A, Hester J, Macklin PS et al. Journal of Clinical Investigation (2019) 129(7) 3640-3656
Gata2 as a Crucial Regulator of Stem Cells in Adult Hematopoiesis and Acute Myeloid Leukemia Menendez-Gonzalez JB, Vukovic M, Abdelfattah A et al. Stem Cell Reports (2019) 13(7) 291-306
Targeting the RNA m6A Reader YTHDF2 Selectively Compromises Cancer Stem Cells in Acute Myeloid Leukemia Paris J, Morgan M, Campos J et al. Cell Stem Cell (2019) 25(7) 137-148.e6
Erratum: Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR (Cell (2019) 177(5) (1201–1216.e19), (S0092867419302806), (10.1016/j.cell.2019.03.018)) Mogilenko DA, Haas JT, L'homme L et al. Cell (2019) 178(7) 263
Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR Mogilenko DA, Haas JT, L'homme L et al. Cell (2019) 177(7) 1201-1216.e19
CpG binding protein (CFP1) occupies open chromatin regions of active genes, including enhancers and non-CpG islands 06 Biological Sciences 0601 Biochemistry and Cell Biology 06 Biological Sciences 0604 Genetics Van De Lagemaat LN, Flenley M, Lynch MD et al. Epigenetics and Chromatin (2018) 11(7)
Ca2+tapulting HSCs into action Guitart AV, Finch AJ, Kranc KR Journal of Experimental Medicine (2018) 215(7) 1971-1973For additional publications, please click here
Andrea Tavosanis, David Wotherspoon, Jasmin Paris, Kay Kong, Elise Chloé Cécile Georges
Aimee Susan Paterson
I obtained my medical degree in Poland (1994-2000) and pre-doctoral research training at the University of Oxford (1998-2000). I was awarded DPhil in Biochemistry from Lincoln College at the University of Oxford (2000-2003) where I held a Wellcome Prize PhD Studentship, Overseas Research Studentship and a Keith Murray Senior Scholarship. I obtained my postdoctoral training at the MRC Human Immunology Unit in Oxford (2003-2007). I was then a Junior Principal Investigator and a Beit Memorial Fellow at the MRC Molecular Haematology Unit at Oxford (2007-2010) and subsequently a Group Leader at the Paul O’Gorman Leukaemia Research Centre at the University of Glasgow (2010-2013). I joined the MRC Centre for Regenerative Medicine in 2013 as a CRUK Senior Fellow and Chair of Molecular Haematology. I was a member of the Edinburgh Cancer Research Centre.
I joined Barts Cancer Institute in 2018.