Dr Andrew Streets BSc MSc PhD
Senior Research Fellow in Nephrology
Department of Infection, Immunity & Cardiovascular Disease
University of Sheffield
Beech Hill Road
Tel: +44 (0)114 215 9555
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 an RCUK Academic Fellowship in 2006 with support from the Sheffield Kidney Research Foundation. I currently hold the title of Senior Research Fellow in Nephrology.
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 also have a keen interest in the role of microRNAs in ADPKD. We and others have shown that alterations in miRNA may contribute to the pathogenesis of ADPKD as well as acting as novel biomarkers. We have carried out microarrays as well as Next Generation Sequencing to identify changes in miRNAs in ADPKD. My work aims to understand the function of these dysregulated miRNAs in ADPKD.
I teach on the following courses:
- Molecular Biology and Biochemistry undergraduate module MBB334
- MSc Molecular Medicine modules MED6002, 6003 and 6005
My research has been funded by the RCUK, KRUK, SKRF, ERA-EDTA 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.
- Trafficking of the polycystin proteins.
For key publications see below. For a full list of publications click here.
- Xu Y, Streets AJ, Hounslow AM, Tran U, Jean-Alphonse F, Needham AJ, Vilardaga J-P, Wessely O, Williamson MP & Ong ACM (2016) The Polycystin-1, Lipoxygenase, and α-Toxin Domain Regulates Polycystin-1 Trafficking. Journal of the American Society of Nephrology, 27(4), 1159-1173.
- Cantero MDR, Velázquez IF, Streets AJ, Ong ACM & Cantiello HF (2015) The cAMP Signaling Pathway and Direct Protein Kinase A Phosphorylation Regulate Polycystin-2 (TRPP2) Channel Function. Journal of Biological Chemistry, 290(39), 23888-23896.
- Streets AJ, Wessely O, Peters DJM & Ong ACM (2013) Hyperphosphorylation of polycystin-2 at a critical residue in disease reveals an essential role for polycystin-1-regulated dephosphorylation.. Hum Mol Genet, 22(10), 1924-1939.
- Chou C-Y, Streets AJ, Watson PF, Huang L, Verderio EAM & Johnson TS (2011) A crucial sequence for transglutaminase type 2 extracellular trafficking in renal tubular epithelial cells lies in its N-terminal beta-sandwich domain.. J Biol Chem, 286(31), 27825-27835.
- Mao Z, Streets AJ & Ong ACM (2011) Thiazolidinediones inhibit MDCK cyst growth through disrupting oriented cell division and apicobasal polarity.. Am J Physiol Renal Physiol, 300(6), F1375-F1384.
- Streets AJ, Needham AJ, Gill SK & Ong ACM (2010) Protein kinase D-mediated phosphorylation of polycystin-2 (TRPP2) is essential for its effects on cell growth and calcium channel activity.. Mol Biol Cell, 21(22), 3853-3865.
- Streets AJ, Wagner BE, Harris PC, Ward CJ & Ong ACM (2009) Homophilic and heterophilic polycystin 1 interactions regulate E-cadherin recruitment and junction assembly in MDCK cells.. J Cell Sci, 122(Pt 9), 1410-1417. View this article in WRRO
- Feng S, Okenka GM, Bai C-X, Streets AJ, Newby LJ, DeChant BT, Tsiokas L, Obara T & Ong ACM (2008) Identification and functional characterization of an N-terminal oligomerization domain for polycystin-2.. J Biol Chem, 283(42), 28471-28479. View this article in WRRO
- Bai CX, Kim S, Li WP, Streets AJ, Ong AC & Tsiokas L (2008) Activation of TRPP2 through mDia1-dependent voltage gating. EMBO J, 27(9), 1345-1356.
- Parker E, Newby LJ, Sharpe CC, Rossetti S, Streets AJ, Harris PC, O'Hare MJ & Ong ACM (2007) Hyperproliferation of PKD1 cystic cells is induced by insulin-like growth factor-1 activation of the Ras/Raf signalling system.. Kidney Int, 72(2), 157-165.
- Streets AJ, Moon DJ, Kane ME, Obara T & Ong ACM (2006) Identification of an N-terminal glycogen synthase kinase 3 phosphorylation site which regulates the functional localization of polycystin-2 in vivo and in vitro.. Hum Mol Genet, 15(9), 1465-1473. View this article in WRRO
- Streets AJ, Newby LJ, O'Hare MJ, Bukanov NO, Ibraghimov-Beskrovnaya O & Ong ACM (2003) Functional analysis of PKD1 transgenic lines reveals a direct role for polycystin-1 in mediating cell-cell adhesion.. J Am Soc Nephrol, 14(7), 1804-1815.
- Streets AJ, Ibraghimov-Beskrovnaya O & Ong ACM (2002) Polycystin-1 mediates cell-cell adhesion in PKD1 transgenic and non-transgenic lines. J AM SOC NEPHROL, 13, 46A-46A.
- Newby LJ, Streets AJ, Zhao Y, Harris PC, Ward CJ & Ong ACM (2002) Identification, characterization, and localization of a novel kidney polycystin-1-polycystin-2 complex.. J Biol Chem, 277(23), 20763-20773. View this article in WRRO