Dr Andrew Streets

BSc MSc PhD

Clinical Medicine, School of Medicine and Population Health

Research Fellow in Nephrology

a.j.streets@sheffield.ac.uk
+44 114 215 9555

The Medical School

Full contact details

Dr Andrew Streets
Clinical Medicine, School of Medicine and Population Health
The Medical School
Beech Hill Road
Sheffield
S10 2RX

Profile

For enquiries please contact - ClinMed-Operational@sheffield.ac.uk

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.

Research interests

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.

Current projects

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.

Publications

Show: Featured publications All publications

Featured publications

Journal articles

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

All publications

Journal articles

Streets A & Ong A (2020) Post-translational modifications of the polycystin proteins. Cellular Signalling, 72, 109644-109644.
Lannoy M, Valluru MK, Chang L, Abdela-Ali F, Peters DJM, Streets AJ & Ong ACM (2020) The positive effect of selective prostaglandin E2 receptor EP2 and EP4 blockade on cystogenesis in vitro is counteracted by increased kidney inflammation in vivo. Kidney International. View this article in WRRO
Magayr TA, Song X, Streets AJ, Vergoz L, Chang L, Valluru MK, Yap HL, Lannoy M, Haghighi A, Simms RJ , Tam FWK et al (2020) Global microRNA profiling in human urinary exosomes reveals novel disease biomarkers and cellular pathways for Autosomal Dominant Polycystic Kidney Disease. Kidney International. View this article in WRRO
Metzner A, Griffiths JD, Streets AJ, Markham E, Philippou T, Van Eeden FJM & Ong ACM (2020) A high throughput zebrafish chemical screen reveals ALK5 and non-canonical androgen signalling as modulators of the pkd2−/− phenotype. Scientific Reports, 10(1). View this article in WRRO
Feng S, Streets AJ, Nesin V, Tran U, Nie H, Onopiuk M, Wessely O, Tsiokas L & Ong A (2017) The Sorting Nexin 3 Retromer Pathway Regulates the Cell Surface Localization and Activity of a Wnt-Activated Polycystin Channel Complex. Journal of the American Society of Nephrology : JASN, 28(10), 2973-2984. View this article in WRRO
Streets AJ, Magayr TA, Huang L, Vergoz L, Rossetti S, Simms RJ, Harris PC, Peters DJM & Ong ACM (2017) Parallel microarray profiling identifies ErbB4 as a determinant of cyst growth in ADPKD and a prognostic biomarker for disease progression. American Journal of Physiology - Renal Physiology, 312(4), F577-F588. View this article in WRRO
Lannoy M, Abdela-ali F, Streets AJ & Ong ACM (2016) SO053SELECTIVE PROSTAGLANDIN E2 RECEPTOR BLOCKADE FOR THE TREATMENT OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE. Nephrology Dialysis Transplantation, 31(suppl_1), i22-i23.
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, Xu Y & Ong ACM (2015) SuO042POLYCYSTIN-1 TRAFFICKING IS REGULATED BY CAMP DEPENDENT PHOSPHORYLATION OF THE PLAT DOMAIN. Nephrology Dialysis Transplantation, 30(suppl_3), iii63-iii63.
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
Dwek MV, Ross HA, Streets AJ, Brooks SA, Adam E, Titcomb A, Woodside JV, Schumacher U & Leathem AJ (2001) Helix pomatia agglutinin lectin-binding oligosaccharides of aggressive breast cancer. INT J CANCER, 95(2), 79-85.
Baldwin SA, Barros LF, Griffiths M, Ingram J, Robbins EC, Streets AJ & Saklatvala J (1997) Regulation of GLUT1 in response to cellular stress.. Biochem Soc Trans, 25(3), 954-958.
Dwek MV, Brooks SA, Streets AJ, Harvey DJ & Leathem AJ (1996) Oligosaccharide release from frozen and paraffin-wax-embedded archival tissues.. Anal Biochem, 242(1), 8-14.
Streets AJ, Brooks SA, Dwek MV & Leathem AJ (1996) Identification, purification and analysis of a 55 kDa lectin binding glycoprotein present in breast cancer tissue.. Clin Chim Acta, 254(1), 47-61.
Harskamp LR, Perez-Gomez MV, Heida JE, Engels GE, van Goor H, van den Heuvel MC, Streets AJ, Ong ACM, Ortiz A, Gansevoort RT , Drenth JPH et al () The association of urinary epidermal growth factors with ADPKD disease severity and progression. Nephrology Dialysis Transplantation.
Streets AJ, Prosseda PP & Ong ACM () Polycystin-1 regulates ARHGAP35-dependent centrosomal RhoA activation and ROCK signalling. JCI Insight.

Chapters

Streets A & Ong A (2014) TRPP2 in Polycystic Kidney Disease, Pathologies of Calcium Channels (pp. 491-522). Springer Berlin Heidelberg

Conference proceedings papers

Magayr T, Streets A & Ong A (2020) SAT-442 Identification of exosome microRNAs as novel biomarkers for rapid disease progression in autosomal dominant polycystic kidney disease. Kidney International Reports, Vol. 5(3) (pp S185-S185). Abu Dhabi, United Arab Emirates, 26 March 2020 - 29 March 2020. View this article in WRRO
Magayr T, Streets A & Ong A (2019) GLOBAL MICRORNA PROFILING IN HUMAN URINARY EXOSOMES REVEALS NEW DISEASE BIOMARKERS AND CELLULAR PATHWAYS FOR AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD). NEPHROLOGY DIALYSIS TRANSPLANTATION, Vol. 34
Lannoy M, Abdela-ali F, Streets AJ & Ong ACM (2016) SELECTIVE PROSTAGLANDIN E2 RECEPTOR BLOCKADE FOR THE TREATMENT OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE. NEPHROLOGY DIALYSIS TRANSPLANTATION, Vol. 31 (pp 22-23)
Rocío Cantero MD, Velázquez IF, Streets AJ, Ong ACM & Cantiello HF (2016) The Cyclic AMP Signaling Pathway and Direct PKA Phosphorylation Regulate Polycystin-2 (TRPP2) Channel Function. Biophysical Journal, Vol. 110(3) (pp 611a-612a)
Streets AJ, Xu Y & Ong ACM (2015) POLYCYSTIN-1 TRAFFICKING IS REGULATED BY CAMP DEPENDENT PHOSPHORYLATION OF THE PLAT DOMAIN. NEPHROLOGY DIALYSIS TRANSPLANTATION, Vol. 30
Streets AJ, Ibraghimov-Beskrovnaya O & Ong ACM (2003) Regulation of polycystin-1 mediated intercellular adhesion by phosphorylation in renal epithelia cells. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, Vol. 14 (pp 575A-575A)

Research group

PhD Students

Fatima Abdeli-Ali
Debo Adekewola
Tajdida Mayer
Paolo Prosseda
Siavash Rostami Ravi
Devon Smith
Laura Vergoz

Teaching activities

I teach on the following courses:

Molecular Biology and Biochemistry undergraduate module MBB334
MSc Molecular Medicine modules MED6002, 6003 and 6005