We use bioinformatic and functional biology approaches to study genetic kidney disease
Use of genetic technologies such as genotyping and large-scale whole genome sequencing has allowed researchers in the Centre for Genetics and Genomics to gain new insights into the biology underlying a range of kidney diseases. This includes discovery of novel monogenic disorders, such as EAST syndrome and CFHR5 nephropathy, as well as providing key insights into the causes and contributors to a range of more common kidney diseases such as membranous nephropathy, IgA nephropathy and nephrotic syndrome.
Researchers in the Centre are experienced in the use of in vitro, in vivo and bioinformatic methods to study the mechanisms by which genetic variation contributes to disease, including the development of potential novel therapies.
Notable publications from the centre include (full list here and below):
1. Bockenhauer, D. et al. (2009). Epilepsy, ataxia, sensorineural deafness, tubulopathy, and KCNJ10 mutations. New England Journal of Medicine, 360 (19), 1960-1970.
2. Gale, D.P. et al. (2010). Identification of a mutation in complement factor H-related protein 5 in patients of Cypriot origin with glomerulonephritis. LANCET, 376 (9743), 794-801. doi:10.1016/S0140-6736(10)60670-8
3. Stanescu, H.C. et al. (2011). Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy. NEW ENGLAND JOURNAL OF MEDICINE, 364 616-626. doi:10.1056/NEJMoa1009742
4. Klootwijk, E.D. et al. (2014). Mistargeting of peroxisomal EHHADH and inherited renal Fanconi's syndrome. New England Journal of Medicine, 370 129-138.
5. Cabezas, O.R. et al. (2017). Polycystic Kidney Disease with Hyperinsulinemic Hypoglycemia Caused by a Promoter Mutation in Phosphomannomutase 2. Journal of the American Society of Nephrology, doi:10.1681/ASN.2016121312
6. Gale, D.P. et al. (2017). Galactosylation of IgA1 Is Associated with Common Variation in C1GALT1. J Am Soc Nephrol, doi:10.1681/ASN.2016091043
7. Reichold, M. et al. (2018). Glycine Amidinotransferase (GATM), Renal Fanconi Syndrome, and Kidney Failure. Journal of the American Society of Nephrology : JASN, doi:10.1681/asn.2017111179
8. Dufek, S. et al. (2019). Genetic Identification of Two Novel Loci Associated with Steroid-Sensitive Nephrotic Syndrome. J Am Soc Nephrol. 2019 Aug;30(8):1375-1384. doi: 10.1681/ASN.2018101054.
9. Levine, A.P. et al. (2020). Large-Scale Whole-Genome Sequencing Reveals the Genetic Architecture of Primary Membranoproliferative GN and C3 Glomerulopathy. J Am Soc Nephrol. 2020 Feb;31(2):365-373. doi: 10.1681/ASN.2019040433.
10. Turro, E., Astle, W.J., Megy, K., Gräf, S., Greene, D., Shamardina, O., ...Thys, C. (2020). Whole-genome sequencing of patients with rare diseases in a national health system. Nature, doi:10.1038/s41586-020-2434-2
11. Kadkhodayi-Kholghi, N., Bhatt, J.S., Gor, J., McDermott, L.C., Gale, D.P., Perkins, S.J. (2020). The solution structure of the complement deregulator FHR5 reveals a compact dimer and provides new insights into CFHR5 nephropathy. Journal of Biological Chemistry, jbc.RA120.015132. doi:10.1074/jbc.ra120.015132
12. Stubbs, M.J., Coppo, P., Cheshire, C., Veyradier, A., Dufek, S., Levine, A.P., ...Hubank, M. (2021). Identification of a novel genetic locus associated with immune mediated thrombotic thrombocytopenic purpura.. Haematologica, doi:10.3324/haematol.2020.274639
|Professor Daniel Gale|
Head of Centre
|Professor Detlef Bockenhauer|
|Professor Robert Kleta|
|Dr Horia Stanescu|
|Dr Anselm Zdebik|
|Professor Patricia Wilson|
|Dr Omid Sadeghi-Alavijeh|
MRC Doctoral Fellow
|Dr Melanie Chan|
KRUK Doctoral Fellow
|Dr Sanjana Gupta|
|Dr Mallory Downie|
KRESCENT Doctoral Fellow
|Dr Adam Levine|
|Dr Matthew Stubbs|
Clinical doctoral fellow
|Dr Sergio Camilo Lopez Garcia|
|Dr Vaksha Patel|