Dr Andrew Streets BSc MSc PhD
RCUK Academic Fellow
Academic Unit of Nephrology
Department of Infection and Immunity
Sir Henry Wellcome Laboratories for Medical Research
The Universtiy of Sheffield Medical School
Beech Hill Road
Tel: +44 (0)114 271 2365
I obtained a BSc (Hons) from the University of Durham in 1993, an MSc from UCL in 1996 and completed my PhD at the University of Leeds in 2000. I joined the University of Sheffield in 1999 working in the Kidney Genetics Group headed by Professor Albert Ong. After completing a Kidney Research UK Career Development Fellowship I was awarded a RCUK Academic Fellowship in 2006 with support from the Sheffield Kidney Research Foundation.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disease affecting the kidney (incidence 1 in 1000) and is caused by mutations in two genes, PKD1 (85-90%) or PKD2 (10-15%) which encode the polycystin-1 and 2 proteins respectively. Around 10% of patients on renal replacement therapy have ADPKD and it is estimated that this treatment costs £40 million per annum to the NHS alone. There are currently no effective drugs for slowing progression in the 50% of ADPKD patients who are destined to develop end-stage renal failure.
The aim of my current research is to test the hypothesis that the biology of the polycystin-1 and 2 complex is regulated by reversible protein phosphorylation under the control of tightly regulated protein kinases and phosphatases. Reversible phosphorylation regulates protein trafficking, protein-protein interactions and protein functions such as cell-cell adhesion, channel activity and cell signalling. Polycystin-1 and 2 can act either as part of a complex, or as individual proteins to carry out these functions. Understanding this dynamic process will provide important new information which could lead to new treatments to retard cyst formation in ADPKD. My recent work has shown that phosphorylation plays a key role in regulating polycystin-2 function both in vitro and in vivo and that polycystin-1 regulates cell adhesion, both of which are critically important for the maintenance of normal tubular and glomerular morphology.
I currently teach undergraduates in MBB and the Medical School.
My research has been funded by the RCUK, KRUK, SKRF and the Northern General Hospital trustees as well as the Medical School.
My current projects include:
- The role of phosphorylation in the regulation of polycystin-2 function.
- The role of polycystin 1 and 2 in the regulation of cell adhesion.
- The role of microRNAs in the pathogenesis of ADPKD.
- Streets, AJ, Needham, A, Gill, S and Ong AC. Protein Kinase D mediated phosphorylation of polycystin-2 (TRPP2) is essential for its effects on cell growth and differentiation. Mol Biol Cell. 2010, Under revision.
- Streets, AJ, Wagner BE, Harris, PC, Ward CJ & Ong AC. Homophilic and heterophilic polycystin-1 interactions regulate E-cadherin recruitment and junction assembly in MDCK cells. J Cell Science. 2009, 122 1410-7.
- Feng, S, Okenka, GM, Bai, CX, Streets, AJ, Newby, LJ, DeChant, BT, Tsiokas, L, Obara, T & Ong, AC. Identification and functional characterization of an N-terminal oligomerization domain for polycystin-2. J Biol Chem. 2008, 283 28471-9.
- Bai CX, Kim S, Li WP, Streets AJ, Ong AC, Tsiokas L. Activation of TRPP2 through mDia1-dependent voltage gating. EMBO J. 2008, 27 1345-56.
- Parker E, Newby LJ, Sharpe CC, Rossetti S, Streets AJ, Harris PC, O'Hare MJ, Ong AC. Hyperproliferation of PKD1 cystic cells is induced by insulin-like growth factor-1 activation of the Ras/Raf signalling system. Kidney Int. 2007 72 157-65.
- Streets AJ, Moon DJ, Kane ME, Obara T and Ong ACM. Identification of an N-terminal glycogen synthase kinase 3 phosphorylation site which regulates the functional localisation of polycystin-2 in vivo and in vitro. Hum Mol Genet. 2006 15 1465-73.
- Streets AJ, Newby L, O'Hare M, Bukanov N, Ibraghimov-Beskrovnaya O, Ong ACM. Functional analysis of PKD1 transgenic lines reveals a direct role for polycystin-1 in mediating cell-cell adhesion. J Am Soc Nephrol. 2003 14 1804-15.
- Newby LJ, Streets AJ, Zhao Y, Harris PC, Ward CJ, Ong ACM. Identification, characterisation and localisation of a novel kidney polycystin-1/polycystin-2 complex. J Biol Chem. 2002 277 20763-73 (joint first author).
- Dwek MV, Ross HA, Streets AJ, Brooks SA, Adam E, Titcomb A, Woodside JV, Schumacher U, Leathem AJ. Helix pomatia agglutinin lectin-binding oligosaccharides of aggressive breast cancer. Int J Cancer. 2001 95 79-85.
- Baldwin SA, Barros LF, Griffiths M, Ingram J, Robbins EC, Streets AJ, Saklatvala J. Regulation of GLUT1 in response to cellular stress. Biochem Soc Trans. 1997 25 954-958.
- Dwek MV, Brooks SA, Streets AJ, Harvey DJ, Leathem AJ. Oligosaccharide release from frozen and paraffin-wax-embedded archival tissues. Anal Biochem. 1996 242 8-14.
- Streets AJ, Brooks SA, Dwek MV, Leathem AJ. Identification, purification and analysis of a 55 kDa lectin binding glycoprotein present in breast cancer tissue. Clin Chim Acta. 1996 254 47-61.