Dr Alastair Barr

Senior Lecturer

+44 20 7911 5000 ext 64122
115 New Cavendish Street London W1W 6UW

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Biomedical Sciences | Department

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  • 1989 - BSc. (Hons) Pharmacology, University of Glasgow
  • 1994 - DPhil. Pharmacology, University of Oxford

I joined the University of Westminster in 2011 as a Senior Lecturer in Pharmacology and Physiology.  My main research interest is in the structure, function and regulation of protein tyrosine phosphatases and the role of these signalling enzymes in diseases such as cancer, diabetes and cardiovascular disease. 

I graduated with a BSc (Hons) in Pharmacology from the University of Glasgow and a DPhil in Pharmacology from the University of Oxford.  I carried out post-doctoral research with Professor David Manning at the University of Pennsylvania on G protein-coupled receptor signalling supported by an American Heart Association fellowship.  After this I worked as post-doctoral researcher at Duke University, USA in the laboratory of Professor Ralph Snyderman on chemoattractant receptor signalling in immune cells and was subsequently appointed as an Assistant Research Professor.

After a short period in the biotech sector I took up a Team Leader position in the phosphorylation-dependent signalling group with Professor Stefan Knapp at the Structural Genomics Consortium (SGC) Oxford.  At the SGC, I led a project on large-scale structural biology of protein tyrosine phosphatases and also contributed to kinase and membrane protein structural biology projects.

My research uses a combination of cell-based and in vitro assays, molecular biology, protein biochemistry and fluorescence microscopy.

I have numerous peer-reviewed publications in leading scientific and biomedical research journals, have written book chapters and am Guest Editing a collection for the Scientific Video Journal JoVE. I have presented my research at national and international conferences and  I am a member of the British Pharmacological Society and Society for Endocrinology.

I am the Course Leader for the BSc in Human and Medical Science.  I teach on both undergraduate and post-graduate modules, supervise BSc and MSc research Projects, and supervise PhD students. 

Modules: Human Physiology, Systems Pharmacology, Physiological Networks, Medical Physiology, Human Physiological Adaptations, Applied Medical Science, Advanced Pharmacology and Toxicology, Drug Discovery and Immunopharmacology, Cell Signalling and Genetics.

Protein tyrosine phosphatases (PTPs), of both the receptor and non-receptor classes, are key signalling molecules that play critical roles in cellular regulation underlying diverse physiological events.  Aberrant signalling as a result of genetic mutation or altered expression levels has been associated with several diseases, specifically cancer, and pharmacological modulation of PTP activity has been explored as a treatment for several conditions.  The role of the ectodomain in several receptor PTPs is poorly understood.

Specific research projects include:

1) Investigating the functional effects of single nucleotide polymorphisms (SNPs) in receptor- type protein tyrosine phosphatases and linking SNPs with disease

2) Systematically surveying protein-protein interactions for the receptor-type PTP GLEPP1(PTPRO) using novel techniques with the aim of mapping this protein’s interactome

3) Development of PTP inhibitors (both small molecules and biologicals) that may have potential as novel therapeutics

Former PhD students

Myrsini Tsimon

Olga Dorofejeva

 

Applicants to lab

Applicants (visitors, PhD students) interested in working in the laboratory should contact Dr Barr ([email protected]).

Weblinks

The PTP Family Photo Album: http://www.cell.com/cell/fulltext/S0092-8674(09)00012-9

Structures in PDB: https://www.rcsb.org/pdb/results/results.do?tabtoshow=Current&qr...

Jove Methods Collection: https://www.jove.com/methods-collections

2017

Defining the molecular basis of interaction between R3 receptor-type protein tyrosine phosphatases and VE-cadherin (2017)
Dorofejeva, O. and Barr, A.J. 2017. Defining the molecular basis of interaction between R3 receptor-type protein tyrosine phosphatases and VE-cadherin. PLoS ONE. 12 (9 : e0184574.), pp. 1-23.

2016

Automatic Selection of Molecular Descriptors using Random Forest: Application to Drug Discovery (2016)
Cano, G., Garcia-Rodriguez, J., Garcia-Garcia, A, Perez-Sanchez, H., Benediktsson, J.A., Thapa, A. and Barr, A.J. 2016. Automatic Selection of Molecular Descriptors using Random Forest: Application to Drug Discovery. Expert Systems with Applications. 72, pp. 151-159.

2014

Targeting protein tyrosine phosphatase SHP2 for therapeutic intervention (2014)
Butterworth, S., Overduin, M. and Barr, A.J. 2014. Targeting protein tyrosine phosphatase SHP2 for therapeutic intervention. Future Medicinal Chemistry. 6 (12), pp. 1423-1437.

2013

Structures of ABCB10, a human ATP-binding cassette transporter in apo- and nucleotide-bound states (2013)
Shintre, C.A., Pike, A.C.W., Li, Q., Kim, J.I., Barr, A.J., Goubin, S., Shrestha, L., Yang, J., Berridge, G., Ross, J., Stansfeld, P.J., Sansom, M.S.P., Edwards, A.M., Bountra, C., Marsden, B., von Delft, F., Bullock, A.N., Gileadi, O., Burgess-Brown, N.A. and Carpenter, E.P. 2013. Structures of ABCB10, a human ATP-binding cassette transporter in apo- and nucleotide-bound states. Proceedings of the National Academy of Sciences. 110 (24), pp. 9710-9715.

2011

Receptor tyrosine phosphatase PTPγ is a regulator of spinal cord neurogenesis (2011)
Hashemia, H., Hurley, M., Gibson, A., Panova, V., Tchetchelnitski, V., Barr, A.J. and Stoker, A.W. 2011. Receptor tyrosine phosphatase PTPγ is a regulator of spinal cord neurogenesis. Molecular and Cellular Neuroscience. 46 (2), pp. 469-482.
Crystal structures of ABL-related gene (ABL2) in complex with imatinib, tozasertib (VX-680), and a type I inhibitor of the triazole carbothioamide class (2011)
Salah, E., Ugochukwu, E., Barr, A.J., von Delft, F., Knapp, S. and Elkins, J.M. 2011. Crystal structures of ABL-related gene (ABL2) in complex with imatinib, tozasertib (VX-680), and a type I inhibitor of the triazole carbothioamide class. Journal of Medicinal Chemistry. 54 (7), pp. 2359-2367.

2010

Protein tyrosine phosphatases as drug targets: strategies and challenges of inhibitor development (2010)
Barr, A.J. 2010. Protein tyrosine phosphatases as drug targets: strategies and challenges of inhibitor development. Future Medicinal Chemistry. 2 (10), pp. 1563-1576.
CD148 enhances platelet responsiveness to collagen by maintaining a pool of active Src family kinases (2010)
Ellison, S., Mori, J., Barr, A.J. and Senis, Y.A. 2010. CD148 enhances platelet responsiveness to collagen by maintaining a pool of active Src family kinases. Journal of Thrombosis and Haemostasis. 8 (7), pp. 1575-1583.

2009

Large-scale structural analysis of the classical human protein tyrosine phosphatome (2009)
Barr, A.J., Ugochukwu, E., Lee, W.H., King, O.N.F., Filippakopoulos, P., Alfano, I., Savitsky, P., Burgess-Brown, N.A., Muller, S. and Knapp, S. 2009. Large-scale structural analysis of the classical human protein tyrosine phosphatome. Cell. 136 (2), pp. 352-363.
HD-PTP is a catalytically inactive tyrosine phosphatase due to a conserved divergence in its phosphatase domain (2009)
Gingras, M.C., Zhang, Y.L., Kharitidi, D., Barr, A.J., Knapp, S., Tremblay, M.L. and Pause, A. 2009. HD-PTP is a catalytically inactive tyrosine phosphatase due to a conserved divergence in its phosphatase domain. PLoS ONE. Online.

2008

Sequence-specific 1H, 13C and 15N backbone resonance assignments of the 34 kDa catalytic domain of human PTPN7 (2008)
Jeeves, M., McClelland, D.M., Barr, A.J. and Overduin, M. 2008. Sequence-specific 1H, 13C and 15N backbone resonance assignments of the 34 kDa catalytic domain of human PTPN7. Biomolecular NMR Assignments. 2 (2), pp. 101-103.

2006

MAPK-specific tyrosine phosphatases: new targets for drug discovery? (2006)
Barr, A.J. and Knapp, S. 2006. MAPK-specific tyrosine phosphatases: new targets for drug discovery? Trends in Pharmacological Sciences. 27 (10), pp. 525-530.
The crystal structure of human receptor protein tyrosine phosphatase κ phosphatase domain 1 (2006)
Eswaran, J., Debreczeni, J.E., Longman, E., Barr, A.J. and Knapp, S. 2006. The crystal structure of human receptor protein tyrosine phosphatase κ phosphatase domain 1. Protein Science. 15 (6), pp. 1500-1505.
Crystal structure of human protein tyrosine phosphatase 14 (PTPN14) at 1.65-A resolution (2006)
Barr, A.J., Debreczeni, J.E., Eswaran, J. and Knapp, S. 2006. Crystal structure of human protein tyrosine phosphatase 14 (PTPN14) at 1.65-A resolution. Proteins. 63 (4), pp. 1132-1136.
Crystal structures and inhibitor identification for PTPN5, PTPRR and PTPN7: a family of human MAPK-specific protein tyrosine phosphatases (2006)
Eswaran, J., von Kries, J.P., Marsden, B., Longman, E., Debreczeni, J.E., Ugochukwu, E., Turnbull, A., Lee, W.H., Knapp, S. and Barr, A.J. 2006. Crystal structures and inhibitor identification for PTPN5, PTPRR and PTPN7: a family of human MAPK-specific protein tyrosine phosphatases. Biochemical Journal. 395 (3), pp. 483-491.

2002

Phospholipase C-β 2 interacts with mitogen-activated protein kinase kinase 3 (2002)
Barr, A.J., Marjoram, R.J., Xu, J. and Snyderman, R. 2002. Phospholipase C-β 2 interacts with mitogen-activated protein kinase kinase 3. Biochemical and Biophysical Research Communications. 293 (1), pp. 647-652.

2001

RGS4 inhibits platelet-activating factor receptor phosphorylation and cellular responses (2001)
Richardson, R.M., Marjoram, R.J., Barr, A.J. and Snyderman, R. 2001. RGS4 inhibits platelet-activating factor receptor phosphorylation and cellular responses. Biochemistry. 40 (12), pp. 3583-3588.

2000

Function and regulation of chemoattractant receptors (2000)
Haribabu, B., Richardson, R.M., Verghese, M.W., Barr, A.J., Zhelev, D.V. and Snyderman, R. 2000. Function and regulation of chemoattractant receptors. Immunologic Research. 22 (2-3), pp. 271-279.
Identification of a region at the N-terminus of phospholipase C-beta 3 that interacts with G protein beta gamma subunits (2000)
Barr, A.J., Ali, H., Haribabu, B., Snyderman, R. and Smrcka, A.V. 2000. Identification of a region at the N-terminus of phospholipase C-beta 3 that interacts with G protein beta gamma subunits. Biochemistry. 39 (7), pp. 1800-1806.

1999

Differential coupling of the sphingosine 1-phosphate receptors Edg-1, Edg-3, and H218/Edg-5 to the Gi, Gq, and G12 families of heterotrimeric G proteins (1999)
Windh, R., Lee, M.J., Hla, T., An, S., Barr, A.J. and Manning, D.R. 1999. Differential coupling of the sphingosine 1-phosphate receptors Edg-1, Edg-3, and H218/Edg-5 to the Gi, Gq, and G12 families of heterotrimeric G proteins. Journal of Biological Chemistry. 274 (39), pp. 27351-27358.

1998

Differential regulation of formyl peptide and platelet-activating factor receptors: role of phospholipase Cbeta3 phosphorylation by protein kinase A (1998)
Ali, H., Sozzani, S., Fisher, I., Barr, A.J., Richardson, R.M., Haribabu, B. and Snyderman, R. 1998. Differential regulation of formyl peptide and platelet-activating factor receptors: role of phospholipase Cbeta3 phosphorylation by protein kinase A. Journal of Biological Chemistry. 273 (18), pp. 11012-11016.

1997

Agonist-independent activation of Gz by the 5-hydroxytryptamine1A receptor co-expressed in spodoptera frugiperda cells: distinguishing inverse agonists from neutral antagonists (1997)
Barr, A.J. and Manning, D.R. 1997. Agonist-independent activation of Gz by the 5-hydroxytryptamine1A receptor co-expressed in spodoptera frugiperda cells: distinguishing inverse agonists from neutral antagonists. Journal of Biological Chemistry. 272 (52), pp. 32979-32987.
Reconstitution of receptors and GTP-binding regulatory proteins (G Proteins) in Sf9 Cells: a direct evaluation of selectivity in receptor.G protein coupling (1997)
Barr, A.J., Brass, L.F. and Manning, D.R. 1997. Reconstitution of receptors and GTP-binding regulatory proteins (G Proteins) in Sf9 Cells: a direct evaluation of selectivity in receptor.G protein coupling. Journal of Biological Chemistry. 272 (4), pp. 2223-2229.

1994

Protein kinase C mediates delayed inhibitory feedback regulation of human neurokinin type 1 receptor activation of phospholipase C in UC11 astrocytoma cells (1994)
Barr, A.J. and Watson, S.P. 1994. Protein kinase C mediates delayed inhibitory feedback regulation of human neurokinin type 1 receptor activation of phospholipase C in UC11 astrocytoma cells. Molecular Pharmacology. 46 (2), pp. 266-273.

1993

Non-peptide antagonists, CP-96,345 and RP 67580, distinguish species variants in tachykinin NK1 receptors (1993)
Barr, A.J. and Watson, S.P. 1993. Non-peptide antagonists, CP-96,345 and RP 67580, distinguish species variants in tachykinin NK1 receptors. British Journal of Pharmacology. 108 (1), pp. 223-227.

1991

The presence of NK3 tachykinin receptors on rat uterus (1991)
Barr, A.J., Watson, S.P., Bernal, A.L. and Nimmo, A.J. 1991. The presence of NK3 tachykinin receptors on rat uterus. European Journal of Pharmacology. 203 (2), pp. 287-290.

2014

Functional Studies On Receptor-Type Protein Tyrosine Phosphatases Of The R3 Subgroup Using Bimolecular Fluorescence Complementation (BiFC) Assays (2014)
Dorofejeva, O., Dwek, M. and Barr, A.J. 2014. Functional Studies On Receptor-Type Protein Tyrosine Phosphatases Of The R3 Subgroup Using Bimolecular Fluorescence Complementation (BiFC) Assays . Pharmacology 2014. London 16 Dec 2014 British Pharmacological Society.

2009

Large scale structural analysis of protein tyrosine phosphatases (2009)
Barr, A.J. and Knapp, S. 2009. Large scale structural analysis of protein tyrosine phosphatases. in: Bradshaw, R. and Dennis, E. (ed.) Handbook of cell signaling (2nd edition) San Diego, CA Elsevier. pp. 871-876

2000

Recombinant baculovirus receptor systems to study receptor/G-protein communication (2000)
Windh, R., Barr, A.J. and Manning, D.R. 2000. Recombinant baculovirus receptor systems to study receptor/G-protein communication. in: Kenakin, T. and Angus, J.A. (ed.) The Pharmacology of Functional, Biochemical, and Recombinant Receptor Systems Berlin Heidelberg Springer. pp. 335-362

1999

Agonist-promoted GTP[S35]-binding as a probe for receptor.G protein communication in Sf9 cells (1999)
Barr, A.J. and Manning, D.R. 1999. Agonist-promoted GTP[S35]-binding as a probe for receptor.G protein communication in Sf9 cells. in: Manning, D.R. (ed.) G proteins: techniques of analysis Boca Raton, FL CRC Press. pp. 227-246

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