Professor Kamil R. Kranc

MD, DPhil
Clinical Professor of Haematology
CRUK Senior Cancer Research Fellow
Deputy Centre Lead, Group Leader
Email Staff Directory
Research Focus

Our research aims to understand the biology of leukaemia stem cells and identify the mechanisms they use to escape treatments.

Key Publications

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 

Major Funding
  • 2018-2023- Cancer Research UK (Programme Grant), Targeting RNA metabolism to expand haematopoietic stem cells and eradicate acute myeloid leukaemia, £1,822,455
  • 2018-2021- Blood Cancer UK (Project Grant), RNA splicing regulator Jmjd6 as a new tumour suppressor in acute myeloid leukaemia, £250,000
  • 2017-2020- Medical Research Council (Project Grant), Therapeutic targeting of HIF prolyl hydroxylases in acute myeloid leukaemia, £480,000
  • 2013-2019- Cancer Research UK (Senior Fellowship), Hypoxia signalling pathways in normal and leukaemic stem cell functions, £1,679,467
Themes/Keywords
Cancer Cell Biology Stem Cells Leukaemia Centre for Haemato-Oncology
Research

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.

Major Funding
  • 2018-2023- Cancer Research UK (Programme Grant), Targeting RNA metabolism to expand haematopoietic stem cells and eradicate acute myeloid leukaemia, £1,822,455
  • 2018-2021- Blood Cancer UK (Project Grant), RNA splicing regulator Jmjd6 as a new tumour suppressor in acute myeloid leukaemia, £250,000
  • 2017-2020- Medical Research Council (Project Grant), Therapeutic targeting of HIF prolyl hydroxylases in acute myeloid leukaemia, £480,000
  • 2013-2019- Cancer Research UK (Senior Fellowship), Hypoxia signalling pathways in normal and leukaemic stem cell functions, £1,679,467
Recent Publications

JMJD6 promotes self-renewal and regenerative capacity of hematopoietic stem cells Lawson H, Sepulveda C, van de Lagemaat LN et al. Blood Advances (2021) 5(7) 889-899

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)

For additional publications, please click here
Team

Postdoctoral Researchers
Dr Ali Anvari Azar, Dr Joana Monteiro De Campos, Dr Natacha Bohin, Dr Louie Van De Lagemaat, Dr Hannah Lawson, Dr Christopher Mapperley

PhD Students
Andrea Tavosanis, David Wotherspoon, Jasmin Paris, Kay Kong, Elise Chloé Cécile Georges

Visiting Students
Aimee Susan Paterson

Laboratory Technicians
Annika Sarapuu

Biography

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.

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