Haemato-Oncology
The central aim of Professor Kamil Kranc's group is to discover the key mechanisms regulating leukaemic stem cell (LSC) biology and harness this knowledge to selectively eradicate LSCs, thus pioneereing novel and efficient leukaemia therapies.
Our group focuses on discovering cures for acute myeloid leukaemia with an aim to identify novel therapeutic targets for selective elimination of LSCs, without disrupting normal haematopoiesis.
Hypoxia Signalling
Cells use a variety of mechanisms to sense low levels of oxygen (hypoxia) and respond by altering their metabolism and slowing their proliferation. We discovered that unlike their normal counterparts, AML cells are uniquely sensitive to activation of their hypoxia sensing pathways. Building on this insight, we are developing new treatments to exploit this vulnerability to selectively target and eradicate leukemic cells.
Key publications: Guitart et al., Blood, 2013; Vukovic et al., J. Exp. Med., 2015; Vukovic et al., Blood, 2016; Woodley et al., Nat Comms, 2023; Dembitz et al., Leukemia, 2024; Lawson et al., Nature Cancer, 2024
RNA metabolism
The metabolism of RNA including its processing, transport, translation and degradation can have huge impacts upon a cell’s activity, health and behaviour by altering gene expression or activating intracellular pathways. Our research revealed that in comparison to the normal haematopoietic system, AML overexpresses and is critically dependent on mechanisms regulating RNA degradation. We are pursuing translational projects to better understand and target these dependencies in AML and other malignancies.
Key publications: Paris et al., Cell Stem Cell, 2019; Mapperley et al., J. Exp. Med., 2021; Turner et al., eLife, 2022
Haematopoiesis and leukemogenesis
Haematopoiesis is the process by which all blood cells are formed, including red blood cells, platelets and the immune system. This process must continue throughout life and avoid malignant transformation, while retaining the capacity to respond and adapt to stress, inflammation or disease. We work to investigate the fundamental biology of haematopoiesis and the processes underlying leukemic transformation.
Key publications: Guitart et al., J. Exp. Med., 2017; Lawson et al., Stem Cell Reports, 2021; Kucinski et al., Cell Stem Cell, 2024
The Haemato-Oncology Laboratory aims to develop new treatments for Acute Myeloid Leukaemia (AML), a devastating blood malignancy which arises from mutations within haematopoietic stem and progenitor cells (HSPCs). These mutations give rise to leukemic stem cells (LSCs) which can survive current treatments for AML and are responsible for minimal residual disease and eventual relapse.
LSCs retain many characteristics with normal HSPCs, making them difficult to target without harming normal, healthy blood production. By employing multidisciplinary approaches, we aim to identify molecular pathways that are essential for the survival of malignant cells but dispensable for normal haematopoiesis. Following identification and validation of these vulnerabilities, we work to translate our findings into novel, treatments for AML and other blood malignancies that are more effective and less toxic than existing regimes.
Professor Kamil R Kranc
Director of the Centre for In Vivo Modelling & Group Leader:
Haemato-Oncology Group
Professor Kamil R Kranc is the Chair of Haemato-Oncology and Director of the Centre for In Vivo Modelling at The Institute of Cancer Research. His central aim is to discover the key processes governing cancer stem cells in acute myeloid leukaemia, with the goal of selectively targeting these treatment-resistant cells, thus pioneering curative, non-toxic therapies.