PSAILA LAB
MRC Weatherall Institute of Molecular Medicine, University of Oxford
Oxford Branch, Ludwig Cancer Research Institute
PSAILA LAB
Megakaryocytes and Platelets in the Cancer Microenvironment
Discovery of targetable disease mechanisms in Myeloproliferative Neoplasms
Using human bone marrow organoids to model normal and malignant haematopoiesis
Platelets in early detection and molecular profiling of solid tumours
RESEARCH THEMES
Learn more about our main research themes and applications below.
Megakaryocytes are one of the largest and rarest cells in the human body – with a giant cell size and massive, polyploid nucleus. This confers impressive synthetic capacity – and a handful of megakaryocytes release billions of tiny platelets into our bloodstream every day. Platelets, in contrast to their parent megs, have no nucleus at all. One current research project in this area focuses on how physiological megakaryocytes tolerate successive rounds of whole genome duplication, and the implications of this for their genome stability. Another is exploring our recent discovery (Murphy et al, Science 2025) that despite lacking a nucleus, platelets contain a repertoire of DNA fragments, acquired during circulation by ‘hoovering up’ cell free DNA shed by nucleated cells – including cancer cell-derived and free fetal DNA
Modelling blood cancers in the relevant human tissue environment using human bone marrow organoids
Uncovering targetable mechanisms of cancer progression in myeloproliferative mechanisms
Application of state-of-the-art approaches to discover new ways to detect and treat myeloid blood cancers. We are particularly interested in studying the triggers of bone marrow fibrosis (scarring) and inflammation, and how these features play an instructive role in progression from early-stage to advanced cancer. (Li, Colombo, Wang et al, Science Translational Medicine 2024).
Development of iPSC-derived bone marrow organoids that faithfully recapitulate the cellular, molecular and architectural features of native bone marrow, and implementing these for disease modelling, target discovery and validation of therapies in the relevant human tumour microenvironment (Khan et al, Cancer Discovery 2023, Olijnik et al, Nature Protocols 2024).
Targeting mutant calreticulin-driven malignancies
We are particularly interested in applying our human organoid model to study how the tumour microenvironment influences the efficacy of cancer-targeting immunotherapies, including bispecific antibodies, CAR-T cell therapies and ADCs (Rampotas & Wong et al, in revisions, see ASH Abstract 2024, highlighted as one of the 20 'Best of ASH24' abstracts out of >8000 submitted.)
The Cell Biology and Nuclear Dynamics of Megakaryocytes and Platelets
Translating our discoveries to benefit patients with cancer
Our research is at the interface between discovery science and clinical translation, often in collaboration with commercial partners. Beth is a practicing haematologist and specialist in the care of patients with Myeloproliferative Neoplasms, running a portfolio of Phase 1-3 clinical trials with a focus on anti-mutant CALR targeting immune therapies. She is also the Chair of the National Blood Cancer UK MPN Clinical Research Network. Beth co-founded a spin-out company Alethiomics to expedite translation of our research discoveries to the clinic.
MRC WEATHERALL INSTITUTE OF MOLECULAR MEDICINE
https://www.imm.ox.ac.uk/research/units-and-centres/mrc-molecular-haematology-unit
The MRC Weatherall Institute of Molecular Medicine (MRC WIMM) at the University of Oxford was founded in 1989 by Sir David Weatherall to foster research in molecular and cell biology, with the aim of improving human health. It houses around 400 scientists and world-class core facilities. The Molecular Haematology Unity in the MRC WIMM is focused on understanding normal and diseased blood cell production over time
LIFE IN OXFORD
Oxford is home to a world leading academic institution. It is a beautiful and vibrant city surrounded by incredible countryside and within easy reach from London.
GET IN TOUCH
We are always keen to hear from people who are interested in joining the group. Email: bethan.psaila@new.ox.ac.uk
Our philosophy is to create a dynamic and synergistic environment that leverages the strengths of individual researchers, helping them achieve their goals while maximising our impact as a collective. We believe that this commitment to collaborative research and advocating for individuals accelerates our productivity and progress.
We enjoy regular social events, a yearly lab retreat and members of the team are all encouraged to attend relevant national/international meetings and to develop a strong research network. Group members are well supported in writing applications for independent funding and personal fellowships, and there are good opportunities for collaborations with industry.
HUGELY GRATEFUL TO OUR FUNDERS
Please get in touch for more information about our work or if you are interested in joining us: bethan.psaila@ndcls.ox.ac.uk
KEY PUBLICATIONS
Complete List of Published Work: https://www.ncbi.nlm.nih.gov/myncbi/beth.psaila.1/bibliography/public/
PLATELETS SEQUESTER CELL FREE DNA, INCLUDING TUMOR-DERIVED AND FREE FETAL DNA
Murphy L, Inchauspé J, Valenzano G, Holland P, Sousos N, Belnoue-Davis HL, Li R, Jooss NJ, Benlabiod C, Murphy E, Etzioni Z, Shepherd E, Denly L, Biswas S, Chen L, O'Sullivan J, Rimmer MP, Khan AO, Karali CS, Nasreddin N, Hitchcock IS, Koupenova M, Kriaucionis S, Hughes JR, O'Neill E, Vatish M, Rees P, Leedham S, Desborough M, Mead AJ, Schuster-Böckler B, Gregory CD, Psaila B. Science 2025
See News Articles here!
GENERATING HUMAN BONE MARROW ORGANOIDS FOR DISEASE MODELING AND DRUG DISCOVERY
Aude-Anais Olijnik, Antonio Rodriguez-Romera, Zoë C. Wong, Yuqi Shen, Jasmeet S. Reyat, Natalie J. Jooss, Julie Rayes, Bethan Psaila* & Abdullah O. Khan*. Nature Protocols 2024
HUMAN BONE MARROW ORGANOIDS FOR DISEASE MODELLING, DISCOVERY AND VALIDATION OF THERAPEUTIC TARGETS IN HEMATOLOGICAL MALIGNANCIES
Khan AO, Colombo, M, Reyat JS, Wang G, Rodriguez-Romera R, Wen WX, Murphy L, Grygielska B, Mahoney C, Stone A, Croft A, Bassett D, Poologasundarampillai G, Roy A, Gooding S, Rayes K, Machlus KM, Psaila B. Cancer Discovery 2023. Altimetric Score 260. 6th highest scoring article for this journal for outputs of a similar age.
A PRO-INFLAMMATORY STEM CELL NICHE DRIVES MYELOFIBROSIS THROUGH A TARGETABLE GALECTIN 1 AXIS
Rong L, Colombo M, Wang G, Clark SA, Rodriguez-Romera A, Meng Y, Khan AO, Wen WX, Sousos N, Brierley C, O’Sullivan J, Simoglou Karali C, Murphy L, Sirunkunwattna K, Norfo R, Cheng Q, Teixeira Carrelha J, Ren Z, Rabinovich GA, Rathinam V, Taylor S, Thongjuea S, Royston D, Mead AJ, Psaila, B$. Science Translational Medicine, 2024
CHROMOTHRIPSIS ORCHESTRATES LEUKEMIC TRANSFORMATION IN BLAST PHASE MPN THROUGH TARGETABLE AMPLIFICATION OF DYRK1A
Brierley CK, Yip BH, Orlando G, Goyal H, Wen S, Wen J, Levine MF, Jakobsdottir GM, Rodriguez-Meira A, Adamo A, Bashton M, Hamblin A, Clark SA, O’Sullivan J, Murphy L, Olijnik AA, Cotton A, Narina S, Pruett-Miller SM, Enshaei A, Harrison
C, Drummond M, Knapper S, Tefferi A, Antony-Debré I, Thongjuea S, Wedge DC, Constantinescu S, Papaemmanuil E, Psaila B, Crispino JD, Mead AJ. Nature Genetics 2025.
THE MANAGEMENT OF MYELOFIBROSIS: A BRITISH SOCIETY FOR HAEMATOLOGY GUIDELINE
McLornan, DP, Psaila B, Ewing J, Innes A, Arami S, Brady J, Butt N, Cargo C, Cross, NCP, Francis S, Frewin R, Garg M, Godfrey A, Green A, Khan A, Knapper S, Lambert J, McGregor A, McMullin MF, Nangalia J, Neelakantan P, Woodley C, Mead AJ, Somervaille T, Harrison CN. British Journal of Haematology 2024
2020
SINGLE-CELL ANALYSES REVEAL ABERRANT PATHWAYS FOR MEGAKARYOCYTE-BIASED HEMATOPOIESIS IN MYELOFIBROSIS AND IDENTIFY MUTANT CLONE-SPECIFIC TARGETS
Psaila B*, Wang G*, Rodriguez Meira A, Li R, O’Sullivan J, Heuston E, Anderson S, Senis Y, Voegtle T, Weinberg O, Calicchio M, Milojkovic D, Roberts I, Bodine D, Thongjuea, S*, Mead AJ*. Molecular Cell 2020 May 7th; 78:477-492
2016
SINGLE-CELL PROFILING OF HUMAN MEGAKARYOCYTE-ERYTHROID PROGENITORS IDENTIFIES DISTINCT MEGAKARYOCYTE AND ERYTHROID DIFFERENTIATION PATHWAY.
Psaila B, Barkas, N, Iskander D, Roy, A, Anderson S, Ashley, N, Caputo, V.S, Lichtenberg, J, Loaiza, S, Bodine, D, Karadimitris A, Mead A.J., Roberts I. Genome Biology Single-cell Omics Special Edition 2016 May 3; 17:83.
2012
IN VIVO EFFECTS OF ELTROMBOPAG ON PLATELET FUNCTION IN IMMUNE THROMBOCYTOPENIA: NO EVIDENCE OF PLATELET ACTIVATION.
Psaila B, Bussel JB, Linden MD, Babula B, Li Y, Barnard MR, Tate C, Mathur K, Frelinger AL, Michelson AD. Blood. 2012 Apr 26;119(17):4066-72.