Dr Daniyal Jafree, David Long and Dr Claire Walsh

Dr Daniyal Jafree is an early-career clinician-scientist, working as an Academic Foundation Year 1 (FY1) Doctor in the East of England Deanery, whilst serving as a part-time Postdoctoral Research Fellow at University College London (UCL), supported by a Foulkes Foundation fellowship.

Dr Jafree completed a PhD in the Developmental Biology & Cancer Program at UCL Great Ormond Street Institute of Child Health (GOSICH) supervised by Prof David Long. His recent scientific contributions have been at the intersection of vascular biology and organ development and disease, where we developed workflows for wholemount immunolabelling, optical clearing and three-dimensional 3D imaging of intact biological tissues (Jafree et al. Methods Mol Biol. 2020) which have been used to decipher how the lymphatic vasculature of the kidney develops in mouse and human embryos (Jafree et al. eLife 2019; Jafree et al. J Am Soc Nephrol. 2020).

Dr Jafree is now applying 3D imaging, single-cell RNA sequencing and in vivo imaging modalities of genetically engineered mice or patient samples to study the vasculature in renal pathology and cancer.

He has experience in a wide variety of biomedical research techniques including mouse husbandry, PCR, flow cytometry, histology and immunohistochemistry, advanced imaging techniques including confocal and two-photon microscopy, lightsheet fluorescence microscopy and high resolution episcopic microscopy and computational techniques including the analysis of single-cell RNA sequencing data and 3D image analysis.

Dr Jafree’s ambition is to combine his scientific background with his clinical commitments to generate a programme of work deciphering the role of the vasculature in human health, inflammation, and malignancy and to exploit the vasculature as a therapeutic target for patient benefit.

David Long is a Professor in Paediatric Nephrology and Wellcome Trust Investigator in Science at the UCL Great Ormond Street Institute of Child Health (GOSICH) where he leads a team of over 15 scientists and clinicians who combine innovative imaging approaches with pre-clinical models and human samples to understand and develop new treatments for kidney disease in children and adults.

David’s initial research experience was gained under the supervision of Professor Adrian Woolf as an MRC-funded PhD student (1999-2003). He was then awarded a UCL Bogue Research Fellowship to work with Professor Richard Johnson at the University of Texas, before returning to GOSICH to establish his own research group supported by a Senior Non-Clinical Fellowship from Kidney Research UK (2008-2014) and an MRC New Investigator Award (2012-6).

David’s work has been recognised nationally and internationally with over 70 published papers in high-impact journals and research funding over £8 million. David has also co-edited a textbook describing innovative Molecular Methods in Diabetic Nephropathy and regularly invited to lecture on both his research and scientific career.

He is highly committed to training the next generation of researchers and has supervised 17 PhD students and 11 post-doctoral science and clinical fellows. David was also a member of the Kidney Research UK Research Grants Committee (2014-22), and currently a member of the Journal of the American Society of Nephrology editorial board.

His most recent work is supported by a Wellcome Trust Investigator Award in Science examining how specialised tubes called lymphatic vessels, which clear away excess fluid, immune cells, and debris, grow, work and ‘talk’ to other cells in growing or diseased organs. Lymphatics have been difficult to study using conventional histological techniques but through three-dimensional imaging coupled with mathematical modelling Professor Long’s group have begun to understand how lymphatics arise in the developing kidney in the first place and how they then go wrong in diseases such as cystic kidneys, transplant rejection, diabetes, and kidney cancer.

These findings have led to his and other groups developing lymphatic therapy as a new treatment for kidney disease, providing a new potential therapeutic direction for these patients. Working with colleagues at UCL and the European Synchrotron Research Facility, the Long group have also been examining new ways to image intact human kidneys at a greater depth than current hospital scans obtained through ultrasound or CT.

Using a revolutionary technology called Hierarchical Phase-Contrast Tomography (HiP-CT) and through the Human Organ Atlas project https://human-organ-atlas.esrf.eu/ the team were able to view the entire human kidney in 3-dimensions, and then zoom down to the level of individual kidney filters and vessels, work published in Nature Methods and Nature Protocols. This new technique will now be applied to kidney disease to provide an overall picture of how the structure of the whole kidney is altered in these conditions.

The imaging work from the group has won several prizes including the Great Ormond Street Hospital ‘A moment of discovery’ imaging competition.

Dr Claire Walsh is a Senior Research Fellow at University College London’s, Department for Mechanical Engineering, Co-director of the Materials and Structures of Matter Group and Director of the Human Organ Atlas Hub. Dr Walsh has been an interdisciplinary scientist throughout her career, with a focus on using and developing imaging techniques and analyses to understand human physiology. 

After completing a PhD in biophysics, imaging bubble dynamics in human SCUBA divers; Dr Walsh joined the interdisciplinary team of Prof. Simon Walker-Samuel and Prof. Rebecca Shipley, at the UCL Centre for Advanced Biomedical Imaging. In this role she integrated multiple imaging modalities (fluorescent microscopy, MRI, bioluminescence, CT etc.) in order to understand blood flow in solid tumours.

During this time, she won an MRC Skills Development Fellowship to create a library of digital tissue phantoms for the validation of computational models underpinning microstructural MRI. Over the course of this fellowship Dr Walsh worked closely with Prof. Long and Dr Jafree to develop an imaging technique named multi-fluorescent high resolution episcopic microscopy, a serial-sectioning 3D fluorescence microscopy technique capable of imaging individual cells and blood vessels in large solid samples; as well as developing the image processing pipelines to extract and quantify biological structures from the image datasets.

In 2020 during the COVID-19 pandemic, Dr Walsh joined an international team, led by Prof. Peter Lee, developing a new Synchrotron X-ray tomography technique at the European Synchrotron Radiation Facility (ESRF) to investigate the effects of COVID-19 on lung microstructure. Within six months the team had demonstrated the feasibility of the method which they called Hierarchical Phase-Contrast Tomography (HiP-CT).

HiP-CT allows imaging of intact human organs with unprecedent resolution, achieving single-cell resolution anywhere within an intact organ. The team went on to show how HiP-CT could be applied not only to lungs, but also to brain, heart, spleen, and kidneys; and demonstrated how the data could be quantified to understand structural properties of human kidney vasculature. The project resulted in new understanding of how the vascular system of the lung was altered during severe COVID-19. Since 2020 the HiP-CT technique and team behind it have grown to be a large international collaboration of over 50 research groups, supported by grants in excess of $7.75M from the Chan Zuckerberg Initiative to develop the technique and build a community of users.

Dr Walsh was awarded the ESRF Young Scientist of the Year in recognition of her work in 2021.  Most recently she was appointed to be the first director of the newly established Human Organ Atlas Hub (HOAHub), an international consortium, formed to develop and apply HiP-CT to mitigate or cure human disease by 2050.