(2020/21) PhD Research Year 4 (CRS)
The Kidney Lymphatic Vasculature: Development, Cellular Origins and Implications for Renal Diseases
Professor David Long, UCL Great Ormond Street Institute of Child Health (Kidney Development and Disease Group, Developmental Biology and Cancer Programme), Faculty of Population Health Sciences. See Iris profile.
Professor Peter Scambler, UCL Great Ormond Street Institute of Child Health (Molecular Medicine Unit, Developmental Biology and Cancer Programme), Faculty of Population Health Sciences. See Iris profile.
PhD Funding Source:
Child Health Research Charitable Incorporated Organisation, UCL MBPhD Programme and the Rosetrees Trust.
I am an MBPhD student in the Kidney Development and Disease Group at UCL Great Ormond Street (GOS) Institute of Child Health. I began an MBBS in Medicine at UCL in 2013. In 2015, I started at UCL GOS Institute of Child Health, examining the mechanisms of birth defects first under the supervision of Andrew Copp and Paul Winyard for a Kidney Research UK-funded intercalated BSc in Surgical Sciences, then under Peter Scambler through a British Society of Developmental Biology-funded Gurdon summer undergraduate studentship. I then completed a year of clinical medicine, whilst gaining experience in clinical research with Joanna Zakrzewska at UCL Eastman Dental Institute. In 2017, I transferred to the UCL MBPhD programme. Now under the supervision of David Long, I have been investigating lymphatic vessels and their formation and function in mammalian kidney development and disease. In late 2019, I returned from a two month-long UCL Bogue Research Fellowship to investigate this further with Norman Rosenblum at the Hospital for Sick Children in Canada.
My current research interests sit at the interface of vascular biology and renal medicine. Thus far, I have used advanced imaging technologies to understand how lymphatic vessels grow during mammalian kidney development and demonstrated that kidney lymphatics are malformed in the early stages of polycystic kidney disease. I also collaborate on research projects on role of lymphatics in paediatric renal cancer, lymphatic vessels in other organ systems, kidney macrophage biology and signalling molecules during renal development. To date, I have published twenty-four research articles and am a co-investigator on two active research grants from Kidney Research UK and one from the Rosetrees Trust. Most recently, I was awarded a PhD Plus award by the Rosetrees Trust to investigate lymphatic dysfunction in mouse models of kidney disease in collaboration with UCL Centre for Advanced Biomedical Imaging. David Long was just awarded a Wellcome Trust Investigator Award in Science to pursue our understanding of kidney lymphatics in development and disease.
Description of PhD Project:
Lymphatic vessels clear tissue fluid, cells and small molecules from most of our organs. Malfunction of lymphatics has been linked to a wide range of diseases, including heart attack, obesity, dementia and cancer. The kidney, responsible for filtering blood and balancing many of the body’s chemical processes, also contains lymphatics. However, what lymphatics do in the kidney is not well understood compared to other organs, and there is very little information on when they appear and how they form in the kidney in the first place.
I apply genetic engineering, a suite of biomedical imaging techniques and single cell transcriptomics to mouse models and patient-derived material to understand how lymphatics form and function in the healthy and diseased kidney. The ultimate aim of this line of work is to exploit kidney lymphatic vessels as a therapeutic target in chronic kidney disease and cancer.
- Research Funding:
Rosetrees PhD Plus Grant 2020-2021. “Integrating computational fluid dynamics and imaging of in vivo perfusion to assess renal lymphatic function in health and polycystic kidney disease” (PhD award)
Rosetrees Trust Small Project Grant 2019-2021. “Spatial mapping and single-cell transcriptomics of kidney lymphatics in Wilms’ tumour” (Co-Investigator)
UCL Bogue Research Fellowship 2019. “Deciphering the cellular origin of a novel lymphatic endothelial progenitor in the mammalian kidney” (PhD fellowship)
Kidney Research UK Innovation Grant 2019-2021. “Using nanobodies for labelling and three-dimensional imaging of intact adult mouse kidneys at single-cell resolution” (Co-Investigator)
Kidney Research UK Paediatric Research Project Grant 2019-2021. “Dissecting the role of macrophages in kidney development” (Co-Investigator)
NIHR Great Ormond Street Hospital BRC Doctoral Support Fund 2019-2020. “Understanding the relationship between Wilms’ tumour and lymphatic vessels” (PhD award)
- Teaching and Supervision:
Secondary supervisor for Intercalated Degree Award (Miss Naomi Morka, 2019) “Investigating how signalling molecules help kidney lymphatics to grow” – funded by Kidney Research UK
Secondary supervisor for Gurdon / Company of Biologists Summer Studentship (Miss Nivetha Manobharath, 2019) “Dissecting the role of macrophages in kidney development” – funded by the British Society of Developmental Biology
Primary supervisor for Child Health Research Studentship (Miss Christie Lau, 2019) “Imaging the developing vasculature in polycystic kidney disease” – funded by UCL Great Ormond Street Institute of Child Health
- Highlighted Publications:
For a full list of publications, click here
Jafree DJ, Long DA, Scambler PJ, Ruhrberg C (2021) Mechanisms and cell lineages in lymphatic vascular development. Angiogenesis. doi: 10.1007/s10456
Jafree DJ, Moulding D, Kolatsi-Joannou M, Perretta Tejedor N, Price KL, Milmoe NJ, Walsh CL, Correra RM, Winyard PJ, Harris PC, Ruhrberg C, Walker-Samuel S, Riley PR, Woolf AS, Scambler P, Long DA (2019) Spatiotemporal dynamics and heterogeneity of renal lymphatics in mammalian development and cystic kidney disease. eLife. 8:e48183, doi: 10.7554/eLife.48183.
Jafree DJ, Long DA (2020) Beyond a Passive Conduit: Implications of Lymphatic Biology for Kidney Diseases. J Am Soc Nephrol. 31:1178-1190
Jafree DJ, Long DA, Scambler PJ, Moulding D (2020) Tissue Clearing and Deep Imaging of the Kidney Using Confocal and Two-Photon Microscopy. Methods Mol Biol. 2067:103-126.
Perretta-Tejedor, Jafree DJ, Long DA (2020) Endothelial-epithelial Communication in Polycystic Kidney Disease: Role of Vascular Endothelial Growth Factor Signalling. Cell Signal. 72:109624.
- Highlighted Awards:
PhD Plus Award (Rosetrees Trust, 2020)
Bogue Research Fellowship (UCL, 2019)
President’s Prize Day: Images in Nephrology Award (Royal Society of Medicine, 2018)
Spirit of School of Life and Medical Sciences Award for Scientific Excellence (UCL, 2018)
Graduate Writing Competition Winner (British Society of Developmental Biology, 2018)
Certificate of Merit for MBBS Year 4 examinations (UCL, 2017)
Dean’s Research Prize (UCL, 2017)
Travel award - 3rd European Academy of Neurology Congress (UCL, 2017)
Travel award - American Society of Nephrology Kidney Week (British Society of Developmental Biology, 2016)
Oral Presentation Prize (European Health Innovation Collaborative Conference, 2016)
Dean’s List (UCL Faculty of Medical Sciences, 2016)
Ken Hobbs’ Prize - iBSc Surgical Sciences (UCL, 2016)
Presentation Prize - iBSc Surgical Sciences (UCL, 2016)
British Society of Developmental Biology Summer Studentship (Company of Biologists, 2016)
Be The Change NHS University Champions (Be The Change Initiative, 2016)
Intercalated BSc Award (Kidney Research UK, 2016)
Zurich Biology Undergraduate Summer Studentship (University of Zurich, 2015)
Simon Walker-Samuel – UCL Centre for Advanced Biological Imaging
Christiana Ruhrberg – UCL Institute of Ophthalmology
Kathy Pritchard-Jones – UCL Great Ormond Street Institute of Child Health
Reza Motallebzadeh – UCL Faculty of Medical Sciences
Adrian Woolf – University of Manchester
Paul Riley – University of Oxford
Menna Clatworthy – University of Cambridge
Norman Rosenblum – The Hospital for Sick Children (Canada)
René Hägerling – Charité Universitätsmedizin Berlin (Germany)