Professor Kamil R. Kranc

Professor Kamil R. Kranc

MD, DPhil
Centre: Haemato-Oncology
Fellowships:
  • CRUK Senior Cancer Research Fellow
Clinical Professor of Haematology, Deputy Centre Lead
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Our research aims to understand the biology of leukaemia stem cells and identify tricks they use to escape treatments.

Postdoctoral Researchers in this group
Dr Ali Anvari Azar, Dr Joana Monteiro De Campos, Dr Natacha Bohin, Dr Louie Van De Lagemaat, Dr Hannah Lawson

PhD Students in this group
Andrea Tavosanis, Christopher Mapperley, David Wotherspoon, Jasmin Paris, Kay Kong, Elise Chloé Cécile Georges

Clinical Research Fellows in this group
Dr Jasmin Paris

Visiting students in this group
Aimee Susan Paterson

Laboratory Technicians in this group
Annika Sarapuu

Research Details

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.

Profile

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.

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- Bloodwise (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

Key Publications

Paris J, Morgan M, Campos J, Spencer GJ, Shmakova A, Ivanova I, Mapperley C, Lawson H, Wotherspoon DA, Sepulveda C, Vukovic M, Allen L, Sarapuu A, Tavosanis A, Guitart AV, Villacreces A, Much C, Choe J, Azar A, van de Lagemaat LN, Vernimmen D, Nehme A, Mazurier F, Somervaille TCP, Gregory RI, O'Carroll D1, Kranc KR.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

Guitart AV, Panagopoulou TI, Villacreces A, Vukovic M, Sepulveda C, Allen L, Carter RN, van de Lagemaat LN, Morgan M, Giles P, Sas Z, Vila Gonzalez M, Lawson H, Paris J, Edwards-Hicks J, Schaak K, Subramani C, Gezer D, Armesilla-Diaz A, Wills JC, Easterbrook A, Coman D, So CWE, O’Carroll D, Vernimmen D, Rodrigues NP, Pollard PJ, Morton NM, Finch A, Kranc KR. Fumarate hydratase (Fh1) is a critical metabolic regulator of haematopoietic stem cell functions. J Exp Med (2017) 214(3), 719-735. PMID: 28202494

Vukovic M, Guitart A, Sepulveda C, Villacreces A, O'Duibhir E, Panagopoulou T, Ivens A, Menendez-Gonzalez J, Iglesias JM, Allen L, Glykofrydis F, Subramani C, Armesilla-Diaz A, Post A, Schaak K, Gezer D, So CWE, Holyoake T, Wood A, O'Carroll D, Ratcliffe P, Kranc KR. 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

Kranc KR, Schepers H, Rodrigues NP, Bamforth S, Villadsen E, Ferry H, Bouriez-Jones T, Sigvardsson M, Bhattacharya S, Jacobsen SE, Enver T. Cited2 is an essential regulator of adult hematopoietic stem cells. Cell Stem Cell (2009) 5, 659-665. PMID: 19951693

Gregersen JW*, Kranc KR*, Ke X, Svendsen P, Madsen LS, Randrup Thomsen A, Cardon LR, Bell JI, Fugger L. Functional epistasis on a common MHC haplotype associated with multiple sclerosis. Nature (2006) 443, 574-577. PMID: 17006452 * joint first authors

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

Postdoctoral Researchers in this group
Dr Ali Anvari Azar, Dr Joana Monteiro De Campos, Dr Natacha Bohin, Dr Louie Van De Lagemaat, Dr Hannah Lawson

PhD Students in this group
Andrea Tavosanis, Christopher Mapperley, David Wotherspoon, Jasmin Paris, Kay Kong, Elise Chloé Cécile Georges

Clinical Research Fellows in this group
Dr Jasmin Paris

Visiting students in this group
Aimee Susan Paterson

Laboratory Technicians in this group
Annika Sarapuu

See other researchers working on:

Blood cancers Leukaemia Stem Cells
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