Prof David Long
Professor of Paediatric Nephrology
Developmental Biology & Cancer Dept
UCL GOS Institute of Child Health
- Joined UCL
- 4th Jan 2005
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
64,000 patients with chronic kidney disease stage 5 (CKD5) 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 CKD5 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
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
imaging 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 inbred
mouse strains, we also discovered that albuminuria, an early sign on glomerular damage, was associated with
increased testosterone, reduced glomerular numbers, a common set of glomerular transcripts; and changes in
extracellular 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 early
development 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.
Since 2017, I have been co-module leader (with Professor
Patrizia Ferretti) of CHLD0036, the research project component of the MSc in
Cell 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 Research
Supervision Award as part of the UCL student choice awards.
I have supervised fifteen PhD students acting as the primary
supervisor for nine of these students and line managed
eleven postdoctoral fellows (one who was 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 three long-term visitors for 6-12 month periods on the European Renal
Association, ERAMUS fellowship and University of Leeds BSc research placement
Current PhD students in the laboratory:
Daniyal Jafree (Co-supervisor:
Prof Peter Scambler) "Unravelling the origins of the renal lymphatics."
Funded by Child Health PhD studentship, GOSICH and Rosetrees Trust.
Gideon Pomeranz (Co-supervisors: Dr D Osborn,
Prof A Woolf). “Drug discovery for diabetic kidney disease: using the
zebrafish 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 urethral
valves.” Funded by Royal College of Surgeons
Lauren Russell (Co-supervisors: Prof P Winyard,
Prof N Rosenblum). “Indian hedgehog, a key signalling system in kidney
development 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 their
potential as a therapeutic target.” Funded by Diabetes UK.
- University College London
- Doctorate, Doctor of Philosophy | 2003
- University of Southampton
- First Degree, Bachelor of Science (Honours) | 1999
I am a Professor in Paediatric
Nephrology and a Wellcome Trust Investigator in Science based in the Developmental
Biology and Cancer theme 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 10-12 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 65 published papers in
high-impact journals including eLife, Proc Natl Acad Sci, Journal of the
American Society of Nephrology, Kidney International, Nature Reviews Nephrology
and Diabetes. My articles have been cited over 3400 times and I have an H-index
of 31. 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 am also a member
of the Kidney Research UK Research Grants Committee, 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. I also lead a international consortium funded by Wellcome LEAP using regenerative medicine techniques to engineer functional human kidneys and urinary tracts.