Psaila Group - Developing improved models of normal and malignant blood cell development
- Bethan Psaila
About the Research
I am a Clinician Scientist and lead the bone marrow microenvironment, megakarycyte and myeloid biology lab (the M3BL) at the MRC Weatherall Institute of Molecular Medicine. The research in our lab has a strong translational focus, looking to uncover novel aspects of biology that may help ameliorate clinical challenges. We aim to generate biological insights, experimental tools and research outputs that are widely impactful, resulting in high-impact publications, patents and excellent training opportunities for scientists.
Our science is focused on three themes:
Theme 1: Developing improved tools to study how the bone marrow microenvironment regulates the production of blood cells from stem cells
This includes detailed, ‘multi-omic’ analysis of bone marrow from patients and mouse models at single cell resolution, to understand the cellular cross-talk between stem cells and their niche in healthy and malignant bone marrow (e.g. Li et al, bioRxiv 2023). We also reently developed an exciting human bone marrow organoids model - creating 100s of tiny bone marrows in a dish to understand disease mechanisms and screen new therapies (see Khan et al, Cancer Discovery 2023).
Theme 2: Interrogating megakarycyte and platelet biology
Megakaryocytes – the platelet-producing cells in the bone marrow – are fascinating cells with a unique biology. They undergo whole genome duplication as part of their normal maturation process, often gaining >80-times the nuclear DNA content of other human cells. This gives them a huge synthetic capacity, and they release many proteins that regulate the stem cell niche in bone marrow. In certain blood cancers, they over-produce factors driving fibrosis and the destruction of the bone marrow microenvironment. We aim to better understand how megakaryocytes develop and function, and how they can contribute to cancer (see Psaila et al, Molecular Cell 2020). We are also very interested in how analysing circulating blood platelets can be useful as a ‘liquid biopsy’ tool to screen for cancer and for antenatal screening.
Theme 3: Discovery of clinically-tractable insights into pathogenic mechanisms of myeloid blood cancers
Another major theme is focused on the pathobiology of a type of incurable, chronic blood cancer called ‘myeloproliferative neoplasms’. We are interested in developing and applying state-of-the-art tools to understand why these cancers develop, why patients who present with early blood cancers progress to advanced cancer, and how we can improve treatment pathways. We use these insights to develop and test potential novel strategies for treatments.
Our full list of publications can be found here:
And more details are on these websites:
Please see the Weatherall Institute for Molecular Medicine (WIMM) for information about applications for a DPhil in Medical Sciences with groups based in the WIMM.
Our philosophy is to maintain a dynamic and synergistic environment that fosters and leverages the strengths of researchers, helping individuals to achieve their goals while maximising our impact as a collective. I believe that this commitment to collaborative research and advocating for individuals has greatly accelerated our productivity and outputs.
We offer excellent training opportunities. We use a wide range of experimental techniques including single cell multi-omics, mouse models, cell culture, genome engineering, working with primary patient cells and advanced genetic models. We have a particular interest in applying complex 3D models (organoids) to model disease, develop and test therapies. All students work with a dedicated postdoctoral researcher, providing excellent day-to-day supervison and mentorship. Students will be offered a choice of projects to ensure that it fits with their interests and skills, and will be joining a happy and collegiate group of researchers, who work in close collaboration with several neighboring labs (Mead, Jacobsen, Nerlov labs).
We are fortunate to be a well funded lab, and I encourage trainees to attend national and international conferences to present their work and develop their own research network. I spent >6 years in the US during my training, so have a wide network of friends and collaborators and encourage collaborative projects and placements to learn new skills and experiences.
Given our focus on molecular biology and single cell approaches, many in our team are fluent in computational biology as well as ‘wet lab’ techniques, and we support trainees to attend dedicated computational training courses where appropriate.
In addition to many academic collaborations, we also work closely with industry. Together with Adam Mead who runs a neighboring lab, I co-founded a spin-out company called Alethiomics, part of which is embedded in the lab, and we have filed several patents on recently developed technologies. These links offer excellent training for individuals interested in translational science, relevant for future careers in both academia and industry.
Alumni from the group have an excellent track record with securing independent fellowships, group leader positions and jobs in industry, publishing and academic core facilities.
Students will be enrolled on the MRC WIMM DPhil Course, which takes place in the autumn of their first year. Running over several days, this course helps students to develop basic research and presentation skills, as well as introducing them to a wide-range of scientific techniques and principles, ensuring that students have the opportunity to build a broad-based understanding of differing research methodologies.
Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence and impact. Students are actively encouraged to take advantage of the training opportunities available to them.
As well as the specific training detailed above, students will have access to a wide-range of seminars and training opportunities through the many research institutes and centres based in Oxford.
All MRC WIMM graduate students are encouraged to participate in the successful mentoring scheme of the Radcliffe Department of Medicine, which is the host department of the MRC WIMM. This mentoring scheme provides an additional possible channel for personal and professional development outside the regular supervisory framework. The RDM also holds an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.
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 (impact factor 39.4). Altimetric Score 260 (5th highest scoring article for journal for outputs of a similar age)
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 (impact factor 19.3).
Developmental stage- and site-specific transitions in lineage specification and gene regulatory networks in human hematopoietic stem and progenitor cells. Roy A, Wang G, Iskander D, O’Byrne S, Elliott N, O’Sullivan J, Buck G, Heuston E.F, Wen W.X, Rodriguez Meira A., Hua P, Karadimitris A, Mead AJ, Bodine D, Roberts I, Psaila B* & Thongjuea S*. *equal contribution. Cell Reports 2021 (impact factor 10).
Sousos N, Leathlobhair MN, Simoglou Kaaral C, Louka E, Bienz N, Royston D, Clark SA, Hamblin A, Howard K, Matthews V, George B, Roy A, Psaila B, Edge DC, Mead AJ. In Utero Origin of Myelofibrosis Presenting in Adult Monozygotic Twins After a Prolonged Disease Latency. Nature Medicine 2022 (Impact Factor 87).
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$. Basophils and mast cells orchestrate cancer-associated inflammation and fibrosis via TNF-NFKB-galectin 1 signalling. bioRxiv 2023.
O'Sullivan JM, Mead AJ, Psaila B. Single-cell methods in myeloproliferative neoplasms: old questions, new technologies. Blood. 2023 Jan 26;141(4):380-390. doi: 10.1182/blood.2021014668