Dr Richard Sandford
Personal home page: http://www.cimr.cam.ac.uk/investigators/sandford/index.html
PubMed journal articles - click here
Dr Richard Sandford is pleased to consider applications from prospective PhD students.
My research focusses on the function of the PKD1 gene family. Mutations in PKD1 cause autosomal dominant polycystic kidney disease (ADPKD). PKD1 encodes polycystin-1, a large cell-surface protein of unknown function. Using biochemical, molecular and structural techniques we aim to identify extracellular and intracellular ligands and show how they interact with protein domains found in polycystin-1. In addition, mechanisms that target polycystin-1 to the cell surface are being identified. The polycystins have been shown to function as mechanosensitive calcium channels localised to the renal primary cilium. We have shown that members of the classical receptor protein tyrosine phosphatase family interact with the polycystins in the primary cilium. This identifies a novel mechanism for mechanoregulation of ion channel function. Elucidation of the normal function of polycystin-1 will identify key steps in the pathogenesis of ADPKD and potential ways of modifying disease progression.
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Gout AM, Harris PC, Rossetti S, Peters D, Breuning M, Henske EP, Koizumi A, Inoue S, Shimizu Y, Thongnoppakhun W, Yenchitsomanus PT, Deltas C, Sandford R, Torra R, Turco AE, Jeffery S, Fontes M, Somlo S, Furu LM, Smulders YM, Mercier B, Ferec C, Burtey S, Pei Y, Kalaydjieva L, Bogdanova N, McCluskey M, Geon LJ, Wouters CH, Reiterova J, Stekrova J, San Millan JL, Aguiari G, Del Senno L, Ravine D. 2007. Analysis of published PKD1 gene sequence variants. Nat Genet. 39:427-428. J R Forman, S Qamar, E Paci, R Sandford* and J Clarke*. 2005. (* joint corresponding authors) The remarkable mechanical strength of polycystin-1 supports a direct role in mechanotransduction. J. Mol. Biol. 349(4):861-71. C. Boulter, S. Mulroy, S. Fleming, K. Brindle, S, Webb and R. Sandford. Cardiovascular, skeletal and renal defects in mice with a targeted disruption of the Pkd1 gene. PNAS. USA. 98, (2001) 12174-12179.