Overview
The goal of the Leukaemia Biology group is to develop understanding of disease mechanisms in myeloid lineage blood cancers and through doing so to identify candidate therapeutic targets for development through to the clinic.
Recent years have seen significant progress in the development of better therapies for people with blood cancer, with concomitant improvements in response. However, there remains a substantial unmet need for more effective and less toxic treatments.
Much of the focus of the group continues to be on understanding disease mechanisms in acute myeloid leukaemia (AML). This is a blood cancer characterised by a block to normal myeloid lineage differentiation leading to accumulation of myeloid blast cells in bone marrow (BM), with failure of normal blood cell production. Despite much progress in recent years, including the FDA approval of several novel therapies, it remains the case that long term survival from AML remains poor, especially in those over the age of 60.
The group works on understanding how transcription factors and their associated chromatin cofactors sustain myeloid blood cancers such as AML. We recently reported our discovery of how a small molecule bromodomain inhibitor of the acetyltransferases EP300 and CBP induces cell cycle arrest and cellular differentiation in blood cancer, as well as our preliminary data from the early phase clinical trial evaluation of CCS1477, where we see promising signs of clinical activity across a range of haematological malignancies.
Featured Publications

Therapeutic targeting of EP300/CBP bybromodomain inhibition in hematologicmalignancies.
22nd November 2023
EP300/CBP are histone acetyltransferases recruited onto chromatin by oncogenic transcription factors and control the transcriptional program via their activity in enhancer areas. Nicosia et al. offer new promise in targeting EP300/CBP using the small-molecule inhibitor CSS1477 in patients with blood tumours and no other therapeutic options.

Enhancer recruitment of transcription repressors RUNX1 and TLE3 by mis-expressed FOXC1 blocks differentiation in acute myeloid leukemia
21st September 2021
• FOXC1 contributes to a monocyte-macrophage lineage differentiation block in AML • FOXC1 and RUNX1 colocalize on chromatin via interaction of their DNA binding domains • A FOXC1/RUNX1/TLE3 repressor complex limits monocyte gene enhancer activity • FOXC1 depletion in AML initiates widespread redistribution of RUNX1/TLE3 on chromatin

First-in-Human Phase I Study of Iadademstat (ORY-1001): A First-in-Class Lysine-Specific Histone Demethylase 1A Inhibitor, in Relapsed or Refractory Acute Myeloid Leukemia
14th October 2020
Morphologic response to treatment with iadademstat. (A) Representative images of blood smears showing morphologic differentiation from patient 28 (top) at screening (left) and cycle 1(C1), day 21 (D21) (right) and patient 31 (bottom) at screening (left) and C1D14 (right; two images from the same slide and patient are shown, separated by a dotted line).
Meet the group
Here are the members of my lab. They are a great bunch of hard working and accomplished scientists and it is a pleasure to work with them.

Senior Group Leader
Principal Computational Biologist

Postdoctoral Fellow

Senior Scientific Officer
Postdoctoral Fellow
All Institute Publications
https://doi.org/10.1186/s12943-024-02157-x
The PI3K-AKT-mTOR axis persists as a therapeutic dependency in KRASG12D-driven non-small cell lung cancer
12 November 2024
Institute Authors (1)
Amaya Viros
Labs & Facilities
Genome Editing and Mouse Models
Research Group
Skin Cancer & Ageing
12 November 2024
https://doi.org/10.1186/s13045-024-01610-0
The small inhibitor WM-1119 effectively targets KAT6A-rearranged AML, but not KMT2A-rearranged AML, despite shared KAT6 genetic dependency
8 October 2024
Institute Authors (6)
Georges Lacaud, Mathew Sheridan, Michael Lie-a-ling, Liam Clayfield, Jessica Whittle, Jingru Xu
Research Group
Stem Cell Biology
8 October 2024
/wp-content/uploads/2024/11/Annual-Report-2023.pdf
2023 Annual Report
13 September 2024
13 September 2024
https://doi.org/10.1126/science.adh7954
Vitamin D regulates microbiome-dependent cancer immunity
25 April 2024
Institute Authors (1)
Evangelos Giampazolias
Research Group
Cancer Immunosurveillance
25 April 2024
https://doi.org/10.1038/s41684-024-01363-w
Streamlining mouse genome editing by integrating AAV repair template delivery and CRISPR-Cas electroporation
10 April 2024
Institute Authors (1)
Natalia Moncaut
Labs & Facilities
Genome Editing and Mouse Models
10 April 2024
https://www.biorxiv.org/content/10.1101/2023.12.13.568969v1
A novel human model to deconvolve cell-intrinsic phenotypes of genetically dysregulated pathways in lung squamous cell carcinoma
14 December 2023
Institute Authors (3)
Carlos Lopez-Garcia, Caroline Dive, Anthony Oojageer
Research Group
Translational Lung Cancer Biology
14 December 2023
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A note from the Group Leader – Tim Somervaille
Recent years have seen significant progress in the development of better therapies for people with blood cancer, with concomitant improvements in response. However, there remains a substantial unmet need for more effective, and less toxic, treatments. For example, outcomes in acute myeloid leukaemia (AML) are particularly poor in older adults and those with relapsed or refractory disease, and malignancies such as multiple myeloma are incurable for the great majority. The overarching goal of our group at the Cancer Research UK Manchester Institute is to deliver a bench-to-bedside programme of blood cancer research. Much of our effort is focussed on understanding how transcription factors and their associated chromatin cofactors sustain myeloid blood cancers such as AML. In keeping with this, in recent years we have worked with colleagues in pharma and in the clinic to bring forward novel therapies targeting the histone demethylase LSD1, and the bromodomain acetyltransferases EP300 and CBP.