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Prof David Long
Professor of Paediatric Nephrology
Developmental Biology & Cancer Dept
UCL GOS Institute of Child Health
- Joined UCL
- 4th Jan 2005
Research summary
I have a strong kidney translational research mission which aims to understand mechanisms which underlie kidney disease in children and adults with the goal of translating these findings for patient benefit. To do this, my group combines experimental models of kidney disease using zebrafish, transgenic mice and patient samples with innovative technologies including three-dimensional imaging, mathematical modelling, gene editing, stem cell technology and novel therapeutic approaches. Our work is important as the UK has 70,000 patients with end stage kidney disease (ESKD) requiring either dialysis or transplantation. Life on dialysis has a shorter expectancy than for some cancers, renal transplants are in short supply and the annual cost of the UK ESKD programme is conservatively estimated to be £1 billion or 2% of the National Health Service budget. Therefore, new treatments are urgently required for CKD5.
My laboratory has made several important contributions to the field including:
1) Pioneering VEGF-C therapy for polycystic kidney disease (PKD), a new direction for PKD treatments which had predominately focused on targeting cyst epithelia. Our manuscript (J Am Soc Nephrol 2016,27:69-77) had considerable impact and received widespread media attention.
2) Outlining the spatial and temporal dynamics of kidney lymphatic development in mice and humans using three-dimensional confocal imaging and quantitative analysis (eLife 2019,doi: 10.7554/eLife.48183). We used the maging pipeline to demonstrate abnormal lymphatic patterning in the early stages of PKD. This work was the basis of a recently Wellcome Trust Investigator award.
3) Identifying molecular mechanisms which contribute to glomerular disease which may represent new treatment targets including thymosin-β4 (Kidney Int. 2016,90:1056-1070), planar cell polarity, (J Pathol. 2018,246:485- 496) soluble Nogo-B (Diabetes 2019,68:1841-1852) and pseudouridylation (PNAS 2020,117:15137-15147). Using in-bred mouse strains, we also discovered that albuminuria, an early sign on glomerular damage, was associated withincreased testosterone, reduced glomerular numbers, a common set of glomerular transcripts; and changes inextracellular matrix composition (Kidney Int 2013,83:1118-1129; J Am Soc Nephrol 2015,26:3021-3034). This work provided insights into why different races and genders are more susceptible to kidney disease.
4) Finding that Celsr1, a gene involved in planar cell polarity (PCP), is required for ureteric tree growth in earlydevelopment and later in gestation prevents tubule overgrowth (Kidney Int. 2016,90:1274-1284). We found an interaction between Celsr1 and Vangl2 (another PCP gene) in ureteric tree growth and discovered that these genes together are required for glomerular maturation. We also reported the first association between mutations in PCP genes and a higher incidence of renal malformations.
5) Pioneering work examining angiopoietins in the kidney including: (i) gene therapy studies to manipulate angiopoietins in kidney injury (Kidney Int 2008,74:300-309); (ii) modulating glomerular levels of angiopoietin-1 as a therapy for diabetic nephropathy (J Am Soc Nephrol 2014,25:33-42); (iii) discovering angiopoietin-2 as a biomarker for children with kidney disease (PLoS One 2013,8:e56273). This work has led to several academic groups and pharmaceutical companies working on manipulating angiopoietins as a therapy for kidney disease.
Teaching summary
Since 2017, I have been co-module leader (with ProfessorPatrizia Ferretti) of CHLD0036, the research project component of the MSc inCell and Gene Therapy at GOSICH. I have also supervised 10 BSc and 16 MSc research and literature projects across multiple degrees at UCL. My laboratory has hosted many short-term summer students from different research backgrounds including the InScience and Brunel/GOSICH studentship schemes. Many of the placement students have gone on to obtain successful degrees and are working in scientific fields. I was also nominated in 2019 for the Outstanding ResearchSupervision Award as part of the UCL student choice awards.
I have supervised seventeen PhD students acting as the primary supervisor for ten of these students and line managed eleven postdoctoral fellows (two were awarded their own Kidney Research UK Fellowship, two obtained lectureships at GOSICH and the University of Kent), three research assistants and a Wellcome Trust MD/PhD clinical fellow. I have hosted long-term visitors for 6-12 month periods on the European RenalAssociation, ERAMUS fellowship and University of Leeds BSc research placement schemes.
Current PhD students in the laboratory:
Gideon Pomeranz (Co-supervisors: Dr D Osborn, Prof A Woolf). “Drug discovery for diabetic kidney disease: using thezebrafish as a model.” Funded by Diabetes UK
Kevin Cao (Co-supervisors: Prof C Fry, Prof P Winyard). “The molecular basis of bladder dysfunction in posterior urethralvalves.” Funded by Royal College of Surgeons
Lauren Russell (Co-supervisors: Prof P Winyard,Prof N Rosenblum). “Indian hedgehog, a key signalling system in kidneydevelopment and disease.” Funded by Kidney Research UK.
Saif Malik (Co-supervisor: Dr T Kalber, Dr J Chandler) “Regenerating the kidney by restoring the renal microvasculature” Funded by BBSRC LiDO program.
Tahmina Aktar (Co-supervisor: Prof L Gnudi) “Exploring the contribution of lymphatics towards diabetic kidney disease and theirpotential as a therapeutic target.” Funded by Diabetes UK.
Maria Caluianu (Co-supervisor: Prof P Gissen) "Understanding and treating kidney disease in arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome". Funded by MRC.
Education
- University College London
- Doctorate, Doctor of Philosophy | 2003
- University of Southampton
- First Degree, Bachelor of Science (Honours) | 1999
Biography
I am a Professor in Paediatric Nephrology, Wellcome Trust Investigator in Science and Deputy Head of the Developmental Biology and Cancer Research and Teaching Department at the UCL Great Ormond Street Institute of Child Health (GOSICH) with experience in the renal and vascular biology fields. My initial research experience was gained in the Nephro-Urology Unit at GOSICH under the supervision of Professor Adrian Woolf as an MRC-funded PhD student. Following my PhD, I was awarded a UCL Bogue Research Fellowship to work with Professor Richard Johnson at the University of Texas, then Florida, expanding my knowledge of models of renal disease. I returned to GOSICH and worked as a postdoctoral scientist with Professor Woolf and Professor Paul Winyard. During this time, I developed my own research interests, particularly in the field of podocyte biology and diabetes, leading to a successful grant proposal to study angiopoietin signalling in the renal glomerulus awarded as a Senior Non-Clinical Fellowship by Kidney Research UK in April 2008.
By obtaining further external grant funding (including a MRC New Investigator Award in 2012 and project grants as a principal investigator from the MRC, Kidney Research UK, Diabetes UK, Kids Kidney Research and the GOSICH Children’s Charity) I developed my own research group at UCL. The group has expanded to over 15 members and I am one of the few non-clinical scientists leading a renal group in the UK. My work has been recognised nationally and internationally with over 70 published papers in high-impact journals including eLife, Proc Natl Acad Sci, Journal of the American Society of Nephrology, Kidney International, Nature Reviews Nephrology, Nature Methods and Diabetes. My articles have been cited over 4400 times and I have an H-index of 35. I have also co-edited a textbook describing innovative Molecular Methods in Diabetic Nephropathy. I am regularly invited to lecture on my research including keynote lectures at the American Society of Nephrology, FASEB Conference on polycystic kidneys, UK Renal Association, British Microcirculation Society, Kidney Research UK Fellows Day and the International Thymosins Symposia. I was a member of the Kidney Research UK Research Grants Committee (2014-22), and currently an academic editor for the journal PLoS One and a member of the Journal of the American Society of Nephrology editorial board.
My 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. Defects in lymphatics are linked to common and major diseases including heart attacks, obesity, dementia, cancer and kidney disease. Our work will use sophisticated technologies, capable of three-dimensional imaging and reading genes at cellular detail, to discern how lymphatic vessels grow and communicate with neighbouring cells in the kidney. We will examine how these processes are impaired in polycystic kidney disease; the most common genetic renal disorder and will attempt to restore them to normality by using a lymphatic-based therapy directed to the kidney.