Cancer Research UK awards Dr Beth Psaila the Advanced Clinician Scientist Fellowship

Beth Psalia studied medicine at Clare College, Cambridge and University College London Hospitals. Following general medical training/MRCP, Beth undertook a PhD in the role of megakaryocytes in cancer metastasis. This was a collaborative project between Imperial College London and Weill-Cornell University Medical School, New York. Beth undertook her speciality training in Haematology at the Hammersmith Hospital as an NIHR Academic Clinical Lecturer at Imperial. After completing the clinical training, Beth secured a Wellcome Career Development Fellowship, which supported postdoctoral research at the National Human Genome Research Institute, National Institutes of Health, USA and then the MRC Weatherall Institute of Molecular Medicine, University of Oxford.

Beth is a Senior Fellow in Clinical Medicine at New College and is currently based at MRC Weatherall Institute of Molecular Medicine and is passionate about encouraging clinicians in training to pursue a joint academic-clinical career path and spends 80% of her time in translational research and 20% in the clinic. She hugely enjoys being able to combine scientific research with clinical practice and the opportunities this offers to engage patients with research and to be able to focus the research on clinically meaningful goals.

Myelofibrosis is a rare but fatal disease in which harmful scarring (“fibrosis”) in the bone marrow develops, destroying the normal bone marrow architecture and preventing it from making blood cells. Megakaryocytes, bone marrow cells that make blood platelets, drive the build-up of this scarring. Patients affected by this disease make too many megakaryocytes that then release signals that stimulate the scarring to develop. Unfortunately, survival for patients with myelofibrosis is poor (typically less than 5-10 years following diagnosis), and around 1 in 5 patients develop a blood cancer – acute leukaemia – which cannot be treated. Currently available treatments help symptoms but do not improve survival or reduce the fibrosis.

In order to tackle this disease, development of new approaches to combat two aspects of the disease are urgently needed:

(1) To develop therapies that can selectively target the myelofibrosis cells but allow normal healthy blood cells to re-grow. The ideal way to do this is using a form of ‘cancer immunotherapy’ – a type of treatment that activates the patients’ own immune system (the defence system against invasion) to destroy only the cancer cells, using a unique combination of markers that they express;

(2) To block the excess growth of megakaryocyte cells and their signals that stimulate the scarring.

In the research proposed for Beth’s recent fellowship, Beth will use state-of-the-art techniques to identify new potential therapies, including studying many thousands of bone marrow cells individually to determine the genes being expressed and the markers that are present on their cell surface.  Beth hopes to use this information to identify features of the disease cells that can be used by the patients’ own immune system to destroy only the cancer cells, leaving healthy cells to grow back. A pioneering technique called Imaging CyTOF, will also be used to directly look at the different types of proteins that are present in biopsies of bone marrow from patients with myelofibrosis.

Beth will also develop a system to make large numbers of megakaryocytes from human stem cells in the laboratory and will turn different genes on and off in these cells to see whether they become diseased. This will help identify what are the genes that make megakaryocytes overgrow, and signal for fibrosis to develop in patients with myelofibrosis, and use a special strain of mice as an animal model, that are modified to allow myelofibrosis cells taken from patients to grow and model the disease so that new treatment can be tested. This work will involve collaborations with industry that Beth will continue to develop during this fellowship to accelerate the translation of her research findings into new treatments for patients. She will also be collaborating with Cedric Ghevaert (Cambridge, UK) and Alexandre Theocharides (Zurich).

Beth has recently secured an Advanced Clinician Scientist Fellowship from Cancer Research UK which will be her primary source of funding for this work and also has funding from Bloodwise, the Kay Kendall Leukaemia Fund and Lab282.

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