1995 BSc (Immunology), University of Glasgow
1998 MB ChB, University of Glasgow
2004 Clinical Research Fellow, Newcastle University
2007 PhD, Newcastle University
2007 Post-doctoral research fellow, Washington University School of Medicine, St Louis, USA
2008 Kidney Research UK clinical training fellow, Edinburgh University
2008 Clinical Lecturer in Renal Medicine, Newcastle University
2009 Raine Award- Renal Association Young Investigator Award
2011 Wellcome Intermediate Research Fellow
Royal Society Pairing Scheme
The Royal Society’s MP-Scientist pairing scheme aims to build bridges between parliamentarians and some of the best scientists in the UK. Dr Kavanagh was paired with Chi Onwurah MP for Newcastle Central and Shadow Minister for Innovation, Science and Digital Infrastructure. Dr Kavanagh gives a personal personal account of his experiences in a 'complement' to the Commons.
In a reciprocal visit, Chi joined the Renal Complement Group to gain first hand experience of Biomedical Research
Kidney Disease in The North East of England
Dan Ashby discusses awareness of kidney disease in the North East with Dr Kavanagh - click to watch
aHUS Screening forms
Understanding the structural and functional mechanisms underlying genetic renal disease
The inherited form of haemolytic uraemic syndrome (atypical HUS), a clinical condition in which patients develop a low platelet count and anaemia in the setting of severe, often irreversible, renal failure, is rare but important due to the high mortality and morbidity seen in affected patients. My work, and that of previous investigators in Professor Tim Goodship’s group, has identified mutations in the genes which code for proteins which participate in the alternative pathway of complement, a key defence system of the body which normally protects against infection. I have identified mutations in the complement regulatory protein factor I and demonstrated that the mutations located in the serine protease part of the protein are functionally significant, as they cause loss of an enzymatic activity, known as ‘cofactor activity’. This prevents appropriate down-regulation of complement activation, leading to damage to the tissues of the kidney. I have also mapped the structural and functional effects of mutations in the C-terminus of the Factor H protein (fH) and demonstrated that there is a detrimental effect on cell surface protection in the kidney which predisposes to aHUS. The C-terminal region is normally responsible for binding C3b and glycosaminoglycans. Using NMR, it can be shown that the mutations in the C-terminal region result in only very limited and localized effects on protein structure. Strikingly, binding studies demonstrated that affinities for C3b or glycosaminoglycans did not correlate with the extent to which all the mutants were found to be impaired in a more physiological assay that measured their ability to inhibit cell surface complement functions of full-length fH. This suggests that disruption of a complex fH-self surface recognition process, involving a balance of affinities for protein and physiological carbohydrate ligands, predisposes to aHUS. Future studies will investigate the cross-talk between the complement and coagulation systems and how this predisposes to aHUS.
Retinal vasculopathy with cerebral leukodystrophy (RVCL) is an autosomal dominant microvascular endotheliopathy. The disease manifestations begin in the fourth or fifth decade with central nervous system degeneration and progressive loss of visual acuity secondary to retinal vasculopathy. Mild-moderate liver and kidney impairment are also seen. We demonstrated that C-terminal truncating mutations in the 3’-5’ DNA exonuclease, TREX1, caused RVCL. We established that these truncated proteins retained exonuclease activity but lost normal perinuclear localization. Future studies will examine the incidence and prevalence of this condition in the U.K.
We also have ongoing research collaborations focusing on pre-eclampsia and age-related macular degeneration
Renal Complement Group
Dr Edwin Wong- MRC Clinical Training Fellow
Rachel Challis - PhD Student
KRUK Legacy meeting york 2012