Professor Kamil R. Kranc
MD, DPhil
Clinical Professor of Haematology
CRUK Senior Cancer Research Fellow
Deputy Centre Lead, Group Leader
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- 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
Themes/Keywords
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- 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
Recent Publications
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(2) 137-148.e6
https://www.ncbi.nlm.nih.gov/pubmed/31031138
CpG binding protein (CFP1) occupies open chromatin regions of active genes, including enhancers and non-CpG islands. van de Lagemaat LN, Flenley M, Lynch MD et al. Epigenetics Chromatin (2018) 11(2) 59
https://www.ncbi.nlm.nih.gov/pubmed/30292235
Ca2+tapulting HSCs into action. Guitart AV, Finch AJ, Kranc KR J Exp Med (2018) 215(2) 1971-1973
https://www.ncbi.nlm.nih.gov/pubmed/30002075
hsa-mir183/EGR1-mediated regulation of E2F1 is required for CML stem/progenitor cell survival. Pellicano F, Park L, Hopcroft LEM et al. Blood (2018) 131(2) 1532-1544
https://www.ncbi.nlm.nih.gov/pubmed/29437554
Fumarate hydratase is a critical metabolic regulator of hematopoietic stem cell functions. Guitart AV, Panagopoulou TI, Villacreces A et al. J Exp Med (2017) 214(2) 719-735
https://www.ncbi.nlm.nih.gov/pubmed/28202494
Adult hematopoietic stem cells lacking Hif-1α self-renew normally. Vukovic M, Sepulveda C, Subramani C et al. Blood (2016) 127(2) 2841-2846
https://www.ncbi.nlm.nih.gov/pubmed/27060169
DUAL FUNCTION OF FUMARATE HYDRATASE IN HAEMATOPOIETIC STEM CELL FATES Guitart AV, Vukovic M, Sepulveda C et al. EXPERIMENTAL HEMATOLOGY (2015) 43(11) S49-S49
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000361417400056&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a
FUMARATE HYDRATASE IS AN ESSENTIAL REGULATOR OF EMBRYONIC AND ADULT HAEMATOPOIETIC STEM CELL Guitart AV, Vukovic M, Sas Z et al. HAEMATOLOGICA (2015) 100(11) 123-123
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000361204901263&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a
HIF-2A IS A TUMOUR SUPPRESSOR IN AML Vukovic M, Guitart AV, Kranc K HAEMATOLOGICA (2015) 100(11) 10-10
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000361204901020&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a
THE ROLE OF 2-OXOGLUTARATE DEPENDENT DIOXYGENASES IN NORMAL HAEMATOPOIESIS AND ACUTE MYELOID LEUKEMIA Sepulveda C, Guitart A, Vukovic M et al. HAEMATOLOGICA (2015) 100(11) 9-9
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000361204901018&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a
Team
Postdoctoral Researchers
Dr Ali Anvari Azar, Dr Joana Monteiro De Campos, Dr Natacha Bohin, Dr Louie Van De Lagemaat, Dr Hannah Lawson
PhD Students
Andrea Tavosanis, Christopher Mapperley, 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.