The role of the factor H-related proteins in kidney disease (360G-Wellcome-212252_Z_18_Z)
The complement factor H-related (FHR) proteins influence susceptibility to kidney and eye (age-related macular degeneration) disease, and to meningococcal infection. The FHR proteins are related to complement factor H (FH), the major negative regulator of complement C3 activation. Unlike FH the biological roles of the FHR proteins remain unclear. Understanding how FHR proteins damage the kidney is very important because they are associated with both rare (C3 glomerulopathy) and common (IgA nephropathy) kidney diseases that lack effective treatments. My key goals are to determine how FHR proteins mediate renal injury and if modulating FHR activity can reduce complement- mediated kidney injury. My experimental program will utilise novel mouse strains, developed during my current fellowship, to determine if absence of FHR proteins reduces kidney injury in experimental nephritis, including IgA nephropathy. I will characterise the mechanisms through which mutant FHR proteins cause C3 glomerulopathy by detailed phenotyping of the first model of FHR-associated C3 glomerulopathy. I will elucidate the mechanism through which accumulation of glomerular C3 causes kidney injury. My program will help us to understand how to manipulate these proteins therapeutically which I predict will reveal a means of modulating complement that is safe and amenable to long-term therapy.
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Grant Details
| Region | London |
| Award Date | 2018-07-17T00:00:00+00:00 |
| Sponsor(s) | Prof Martin Wilkins |
| Internal ID | 212252/Z/18/Z |
| Planned Dates: End Date | 2025-10-31T00:00:00+00:00 |
| Planned Dates: Start Date | 2018-11-01T00:00:00+00:00 |
| Amount Awarded | 1917963 |
| Financial Year | 2017/18 |
| Lead Applicant | Prof Matthew Caleb Pickering |
| Grant Programme: Title | Senior Research Fellowship Clinical Renewal |
| Applicant Surname | Pickering |
| Approval Committee | Science Interview Panel |
| Recipient Org: Country | United Kingdom |
| Recipient Org: City | London |
| Has the grant transferred? | No |
| Research conducted at multiple locations? | No |
| Total amount including partnership funding | 1917963 |