Ian Kerr

Contact

• workRoom D15 University of Nottingham Medical School
  Queen's Medical Centre
  Nottingham
  NG7 2UH
  UK
• work0115 82 30122
• fax0115 82 30103
• ian.kerr@nottingham.ac.uk
• http://www.nottingham.ac.uk/~mbzidk

Teaching Summary

I'm the Director of the Biochemistry Courses ad so have overall responsibility for programme design and delivery. Specifically I convene a module in year 2 that aim to showcase how experimental… read more

Research Summary

My research interests are the mechanisms and structures of proteins involved in transmembrane flux.

In particular, the group works on ATP binding cassette (ABC) transporters which are involved in multidrug efflux from cancer cells, and which are involved in the clinical drug resistance of many tumour types. We have a BBSRC funded project to investigate the pharmacology of ABCG2 in collaboration with Nicholas Holliday and Steve Briddon. We have strong collaborations with the group of Beth Coyle to understand the role played by ABC transporters in pediatric brain tumour drug drug resistance, and with the group of Richard Callaghan to understand the mechanism of human ABC proteins.

More broadly I am interested in all types of transporter proteins and have previously worked on plant auxin transporters and bacterial multidrug pumps. Some very related proteins are involved in ribosomal control (too long a story for here) and I've had a long-standing interest in those.

Methods for studying membrane proteins continue to improve and I've worked with several groups to help improve protein purification for functional activity.

More broadly I am interested in all types of transporter proteins and have previously worked on plant auxin transporters and bacterial multidrug pumps. Some very related proteins are involved in ribosomal control (too long a story for here) and I've had a long-standing interest in those.

Methods for studying membrane proteins continue to improve and I've worked with several groups to help improve protein purification for functional activity.

Selected Publications

• SABNIS, DURGAGAURI H., STORER, LISA C. D., LIU, JO-FEN, JACKSON, HANNAH K., KILDAY, J. P., GRUNDY, RICHARD G., KERR, IAN D. and COYLE, BETH, 2019. A role for ABCB1 in prognosis, invasion and drug resistance in ependymoma SCIENTIFIC REPORTS. 9,
• COX, MEGAN H., KAPOOR, PARTH, BRIGGS, DEBORAH A. and KERR, IAN D., 2018. Residues contributing to drug transport by ABCG2 are localised to multiple drug-binding pockets BIOCHEMICAL JOURNAL. 475, 1553-1567
• MITTRA R, PAVY M, SUBRAMANIAN N, GEORGE AM, O'MARA ML, KERR ID and CALLAGHAN R, 2017. Location of contact residues in pharmacologically distinct drug binding sites on P-glycoprotein. Biochemical pharmacology. 123, 19-28
• WONG, KELVIN, BRIDDON, STEPHEN J., HOLLIDAY, NICHOLAS D. and KERR, IAN D., 2016. Plasma membrane dynamics and tetrameric organisation of ABCG2 transporters in mammalian cells revealed by single particle imaging techniques BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH. 1863(1), 19-29

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I'm the Director of the Biochemistry Courses ad so have overall responsibility for programme design and delivery. Specifically I convene a module in year 2 that aim to showcase how experimental design and analysis can determine correlations and causation between genotype and phenotype. I also make significant contributions to a year 2 proteins module, to a year 3 diabetes and obesity module and run a 3rd year research project for 10-12 students invesitgating bacterial drug pump proteins

• SABNIS, DURGAGAURI H., STORER, LISA C. D., LIU, JO-FEN, JACKSON, HANNAH K., KILDAY, J. P., GRUNDY, RICHARD G., KERR, IAN D. and COYLE, BETH, 2019. A role for ABCB1 in prognosis, invasion and drug resistance in ependymoma SCIENTIFIC REPORTS. 9,
• COX, MEGAN H., KAPOOR, PARTH, BRIGGS, DEBORAH A. and KERR, IAN D., 2018. Residues contributing to drug transport by ABCG2 are localised to multiple drug-binding pockets BIOCHEMICAL JOURNAL. 475, 1553-1567
• KAPOOR, PARTH, HORSEY, AARON J., COX, MEGAN H. and KERR, IAN D., 2018. ABCG2: does resolving its structure elucidate the mechanism? BIOCHEMICAL SOCIETY TRANSACTIONS. 46, 1485-1494
• HEYES, NIALL, KAPOOR, PARTH and KERR, IAN D., 2018. Polymorphisms of the Multidrug Pump ABCG2: A Systematic Review of Their Effect on Protein Expression, Function, and Drug Pharmacokinetics DRUG METABOLISM AND DISPOSITION. 46(12), 1886-1899
• MITTRA R, PAVY M, SUBRAMANIAN N, GEORGE AM, O'MARA ML, KERR ID and CALLAGHAN R, 2017. Location of contact residues in pharmacologically distinct drug binding sites on P-glycoprotein. Biochemical pharmacology. 123, 19-28
• WONG, KELVIN, BRIDDON, STEPHEN J., HOLLIDAY, NICHOLAS D. and KERR, IAN D., 2016. Plasma membrane dynamics and tetrameric organisation of ABCG2 transporters in mammalian cells revealed by single particle imaging techniques BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH. 1863(1), 19-29
• AL-GHAFARI, A. B., PUNJARUK, W., STORER, L. C. D., CARRIER, D. J., HUSSEIN, D., COYLE, B. and KERR, I. D., 2016. Long-term exposure to irinotecan reduces cell migration in glioma cells JOURNAL OF NEURO-ONCOLOGY. 127(3), 455-462
• HORSEY AJ, COX MH, SARWAT S and KERR ID, 2016. The multidrug transporter ABCG2: still more questions than answers. Biochemical Society transactions. 44(3), 824-30
• THEODOULOU, FREDERICA L. and KERR, IAN D., 2015. ABC transporter research: going strong 40 years on BIOCHEMICAL SOCIETY TRANSACTIONS. 43, 1033-1040
• COYLE, BETH, KESSLER, MAYA, SABNIS, DURGAGAURI H. and KERR, IAN D., 2015. ABCB1 in children's brain tumours BIOCHEMICAL SOCIETY TRANSACTIONS. 43, 1018-1022
• DARBY, RICHARD A. J., UNSWORTH, AMANDA, KNAPP, STEFAN, KERR, IAN D. and CALLAGHAN, RICHARD, 2015. Overcoming ABCG2-mediated drug resistance with imidazo-[1,2-b]-pyridazine-based Pim1 kinase inhibitors CANCER CHEMOTHERAPY AND PHARMACOLOGY. 76(4), 853-864
• HAIDER AJ, COX MH, JONES N, GOODE AJ, BRIDGE KS, WONG K, BRIGGS D and KERR ID, 2015. Identification of residues in ABCG2 affecting protein trafficking and drug transport, using co-evolutionary analysis of ABCG sequences. Bioscience reports. 35(4),
• POLLOCK NL, MCDEVITT CA, COLLINS R, NIESTEN PHM, PRINCE S, KERR ID, FORD RC and CALLAGHAN R, 2014. Improving the stability and function of purified ABCB1 and ABCA4: the influence of membrane lipids. Biochimica et biophysica acta. 1838(1 Pt B), 134-47
• WONG K, MA J, ROTHNIE A, BIGGIN PC and KERR ID, 2014. Towards understanding promiscuity in multidrug efflux pumps. Trends in biochemical sciences. 39(1), 8-16
• VAN WONDEREN JH, MCMAHON RM, O'MARA ML, MCDEVITT CA, THOMSON AJ, KERR ID, MACMILLAN F and CALLAGHAN R, 2014. The central cavity of ABCB1 undergoes alternating access during ATP hydrolysis. The FEBS journal. 281(9), 2190-201
• GULATI S, JAMSHAD M, KNOWLES TJ, MORRISON KA, DOWNING R, CANT N, COLLINS R, KOENDERINK JB, FORD RC, OVERDUIN M, KERR ID, DAFFORN TR and ROTHNIE AJ, 2014. Detergent-free purification of ABC (ATP-binding-cassette) transporters. The Biochemical journal. 461(2), 269-78
• OTHMAN RT, KIMISHI I, BRADSHAW TD, STORER LCD, KORSHUNOV A, PFISTER SM, GRUNDY RG, KERR ID and COYLE B, 2014. Overcoming multiple drug resistance mechanisms in medulloblastoma. Acta neuropathologica communications. 2, 57
• DE MARCOS LOUSA C, VAN ROERMUND CWT, POSTIS VLG, DIETRICH D, KERR ID, WANDERS RJA, BALDWIN SA, BAKER A and THEODOULOU FL, 2013. Intrinsic acyl-CoA thioesterase activity of a peroxisomal ATP binding cassette transporter is required for transport and metabolism of fatty acids. Proceedings of the National Academy of Sciences of the United States of America. 110(4), 1279-84
• KAY, C., WOODWARD, K.D., LAWLER, K., SELF, T.J., DYALL, S.D. and KERR, I.D., 2012. The ATP-binding cassette proteins of the deep-branching protozoan parasite Trichomonas vaginalis PLoS Neglected Tropical Diseases. 6(6), e1693
• KAY, C., LAWLER, K., SELF, T. J., DYALL, S. D. and KERR, I. D., 2012. Localisation of a family of complex-forming beta-barrels in the T. vaginalis hydrogenosomal membrane: FEBS Lett FEBS Lett. 586(22), 4038-45
• DORRIAN JM, BRIGGS DA, RIDLEY ML, LAYFIELD R, KERR ID, 2011. Induction of a stress response in Lactococcus lactis is associated with a resistance to ribosomally active antibiotics. FEBS Journal. 278(21), 4015-24
• DE SMET, IVE, VOSS, UTE, LAU, STEFFEN, WILSON, MICHAEL, SHAO, NING, TIMME, RUTH, SWARUP, RANJAN, KERR, IAN, HODGMAN, CHARLIE, BOCK, RALPH, BENNETT, MALCOLM, JÜRGENS, GERD and BEECKMAN, TOM, 2011. Unraveling the evolution of auxin signaling. Plant Physiology. 155, 209-221
• HAIDER, A.J., BRIGGS, D., SELF, T.J., CHILVERS, H.L., HOLLIDAY, N.D. and KERR, I.D., 2011. Dimerization of ABCG2 analysed by bimolecular fluorescence complementation PLoS ONE. 6(10), e25818
• KERR ID, HAIDER AJ and GELISSEN IC, 2011. The Abcg Family Of Membrane-Associated Transporters: You Don't Have To Be Big To Be Mighty. British Journal Of Pharmacology. 164(7), 1767-79
• HUSSEIN, D., PUNJARUK, W., STORER, L.C.D., SHAW, L., OTHMAN, R.T., PEET, A., MILLER, S., BANDOPADHYAY, G., HEATH, R., KUMARI, R., BOWMAN, K.J., BRAKER, P., RAHMAN, R., JONES, G.D.D. and WATSON, S., 2010. Pediatric brain tumor cancer stem cells: cell cycle dynamics, DNA repair, and etoposide extrusion Neuro-oncology. 13(1), 70-83
• CROWLEY, EMILY, O'MARA, MEGAN L, KERR, IAN D and CALLAGHAN, RICHARD, 2010. Transmembrane helix 12 plays a pivotal role in coupling energy provision and drug binding in ABCB1. The FEBS journal. 277(19), 3974-85
• KERR, IAN D, JONES, PETER M and GEORGE, ANTHONY M, 2010. Multidrug efflux pumps: the structures of prokaryotic ATP-binding cassette transporter efflux pumps and implications for our understanding of eukaryotic P-glycoproteins and homologues. The FEBS journal. 277(3), 550-63
• CHUTHAPISITH, S, BEAN, B, COWLEY, G, EREMIN, JM, SAMPHAO, S, LAYFIELD, R, KERR, ID, WISEMAN, J, EL-SHEEMY, M, SREENIVASAN, T, EREMIN, O, 2009. Annexins in human breast cancer: Possible predictors of pathological response to neoadjuvant chemotherapy. European Journal of Cancer. 45(7), 1274-81
• CROWLEY, EMILY, O'MARA, MEGAN L, REYNOLDS, CATHERINE, TIELEMAN, D PETER, STORM, JANET, KERR, IAN D and CALLAGHAN, RICHARD, 2009. Transmembrane helix 12 modulates progression of the ATP catalytic cycle in ABCB1. Biochemistry. 48(26), 6249-58
• FORD, R.C, KAMIS, A, KERR, I.D and & CALLAGHAN, R., 2009. The ABC Transporters: Structural insights into drug transport. In: ECKER, G and CHIBA, P. &MANNHOLD, R., eds., Transporters as Drug Carriers: Structure, Function, Substrates Wiley. 3-49
• CARRIER, DAVID JOHN, ABU BAKAR, NORLIZA TENDOT, LAWLER, KAREN, DORRIAN, JAMES MATTHEW, HAIDER, AMEENA, BENNETT, MALCOLM JOHN and KERR, IAN DEREK, 2009. Heterologous Expression of a Membrane-Spanning Auxin Importer: Implications for Functional Analyses of Auxin Transporters. International journal of plant genomics. 2009, 848145
• DORRIAN J.M. & KERR, I.D., 2009. Can ABC proteins confer drug resistance in micro-organisms without being export pumps?. In: PONTE-SUCRE, A., ed., ABC Transporters in Microorganisms Horizon Press. 45-54
• MCDEVITT, CHRISTOPHER A, COLLINS, RICHARD, KERR, IAN D and CALLAGHAN, RICHARD, 2009. Purification and structural analyses of ABCG2. Advanced drug delivery reviews. 61(1), 57-65
• SWARUP, K., BENKOVÁ, E., SWARUP, R., CASIMIRO, I., PÉRET, B., YANG, Y., PARRY, G., NIELSEN, E., DE SMET, I., VANNESTE, S., LEVESQUE, M., CARRIER, D., JAMES, N., CALVO, V. and LJUNG, K., 2008. The auxin influx carrier LAX3 promotes lateral root emergence. Nature Cell Biology. 10(8), 946-954
• CARRIER, D.J., ABU BAKAR, N.T., SWARUP, R., CALLAGHAN, R., NAPIER, R.M., BENNETT, M.J. and KERR, I.D., 2008. The binding of auxin to the Arabidopsis auxin influx transporter, AUX1 Plant Physiology. 148(1), 529-535
• STORM, JANET, MODOK, SZABOLCS, O'MARA, MEGAN L, TIELEMAN, D PETER, KERR, IAN D and CALLAGHAN, RICHARD, 2008. Cytosolic region of TM6 in P-glycoprotein: topographical analysis and functional perturbation by site directed labeling. Biochemistry. 47(12), 3615-24
• MCDEVITT,, CROWLEY,, HOBBS,, STARR,, KERR, and CALLAGHAN,, 2008. Is ATP binding responsible for initiating drug translocation by the multidrug transporter ABCG2? The FEBS Journal.
• LAWSON, J, O'MARA, M L and KERR, I D, 2008. Structure-based interpretation of the mutagenesis database for the nucleotide binding domains of P-glycoprotein. Biochimica et Biophysica Acta. 1778(2), 376-91
• CALLAGHAN, RICHARD, CROWLEY, EMILY, POTTER, SIMON and KERR, IAN D, 2008. P-glycoprotein: so many ways to turn it on. Journal of Clinical Pharmacology. 48(3), 365-78
• CHUTHAPISITH, S, LAYFIELD, R, KERR, I D and EREMIN, O, 2007. Principles of proteomics and its applications in cancer. The Surgeon. 5(1), 14-22
• CHUTHAPISITH, S, LAYFIELD, R, KERR, ID, HUGHES, C, EREMIN, O, 2007. Proteomic profiling of MCF-7 breast cancer cells with chemoresistance to different types of anti-cancer drugs. International Journal of Oncology. 30(6), 1545-51
• WARNER,, VADOLIA,, LAUGHTON,, KERR, and DOUGHTY,, 2007. Modelling the restoration of wild-type dynamic behaviour in DeltaF508-CFTR NBD1 by 8-cyclopentyl-1,3-dipropylxanthine. Journal of Molecular Graphics and Modelling. 26, 691-699
• KERR, IAN D and BENNETT, MALCOLM J, 2007. New insight into the biochemical mechanisms regulating auxin transport in plants. Biochemical Journal. 401(3), 613-22
• STORM,, O'MARA,, CROWLEY,, PEALL,, TIELEMAN,, KERR, and CALLAGHAN,, 2007. Residue G346 in Transmembrane Segment Six is Involved in Inter-Domain Communication in P-Glycoprotein. Biochemistry. 46(35), 9899-9910
• CLARK, R, KERR, I D and CALLAGHAN, R, 2006. Multiple drugbinding sites on the R482G isoform of the ABCG2 transporter. British Journal of Pharmacology. 149(5), 506-15
• KERR, I. D. and SIMPKINS, N. S., 2006. ABC Transporters and Isothiocyanates LETTERS IN DRUG DESIGN AND DISCOVERY. VOL 3(NUMB 9), 607-621
• MCDEVITT, CHRISTOPHER A, COLLINS, RICHARD F, CONWAY, MICHAEL, MODOK, SZABOLCS, STORM, JANET, KERR, IAN D, FORD, ROBERT C and CALLAGHAN, RICHARD, 2006. Purification and 3D structural analysis of oligomeric human multidrug transporter ABCG2. Structure. 14(11), 1623-32
• CALLAGHAN, RICHARD, FORD, ROBERT C and KERR, IAN D, 2006. The translocation mechanism of P-glycoprotein. FEBS Letters. 580(4), 1056-63
• ROTHNIE, A., STORM, J., MCMAHON, R., TAYLOR, A., KERR, I.D. and CALLAGHAN, R, 2005. The coupling mechanism of P-glycoprotein involves residue L339 in the sixth membrane spanning segment. FEBS Letters. 579(18), 3984-3990
• KERR, I D, REYNOLDS, E D and COVE, J H, 2005. ABC proteins and antibiotic drug resistance: is it all about transport? Biochemical Society Transactions. 33(Pt 5), 1000-2
• SWARUP, R., KARGUL, J., MARCHANT, A., ZADIK, D., RAHMAN, A., MILLS, R., YEMM, A., MAY, S., WILLIAMS, L., MILLNER, P., TSURUMI, S., MOORE, I., NAPIER, R., KERR, I.D. and BENNETT, M.J., 2004. Structure-function analysis of the presumptive Arabidopsis auxin permease AUX1 Plant Cell. 16(11), 3069-3083
• ROTHNIE, A., STORM, J., CAMPBELL, J., LINTON, K.J., KERR, I.D. and CALLAGHAN, R, 2004. The topography of transmembrane segment six is altered during the catalytic cycle of P-glycoprotein. Journal of Biological Chemistry. 279(33), 34913-34921
• KERR, I.D, 2004. Sequence analysis of twin ATP binding cassette proteins involved in translational control, antibiotic resistance, and ribonuclease L inhibition. Biochemical and Biophysical Research Communications. 315(1), 166-173
• CAMPBELL, JEFF D, DEOL, SUNDEEP SINGH, ASHCROFT, FRANCES M, KERR, IAN D and SANSOM, MARK S P, 2004. Nucleotide-dependent conformational changes in HisP: molecular dynamics simulations of an ABC transporter nucleotide-binding domain. Biophysical Journal. 87(6), 3703-15
• STENHAM, D.R., CAMPBELL, J.D., SANSOM, M.S.P., HIGGINS, C.F., KERR, I.D. and LINTON, K.J., 2003. An atomic detail model for the human ATP binding cassette transporter P-glycoprotein derived from disulfide cross-linking and homology modeling FASEB Journal. 17(15), 2287-2289
• BERRIDGE, G., WALKER, J. A., CALLAGHAN, R. and KERR, I. D., 2003. The nucleotide-binding domains of P-glycoprotein. Functional symmetry in the isolated domain demonstrated by N-ethylmaleimide labelling European Journal of Biochemistry. 270(7), 1483-1492
• KERR, IAN D, BERRIDGE, GEORGINA, LINTON, KENNETH J, HIGGINS, CHRISTOPHER F and CALLAGHAN, RICHARD, 2003. Definition of the domain boundaries is critical to the expression of the nucleotide-binding domains of P-glycoprotein. European Biophysics Journal. 32(7), 644-54
• GABRIEL, MARK P, STORM, JANET, ROTHNIE, ALICE, TAYLOR, ANDREW M, LINTON, KENNETH J, KERR, IAN D and CALLAGHAN, RICHARD, 2003. Communication between the nucleotide binding domains of P-glycoprotein occurs via conformational changes that involve residue 508. Biochemistry. 42(25), 7780-9
• KERR, IAN D, 2002. Structure and association of ATP-binding cassette transporter nucleotide-binding domains. Biochimica et Biophysica Acta. 1561(1), 47-64
• ROSENBERG, M. F., VELARDE, G., FORD, R. C., MARTIN, C., BERRIDGE, G., KERR, I. D., CALLAGHAN, R., SCHMIDLIN, A., WOODING, C. and LINTON, K. J., 2001. Repacking of the transmembrane domains of P-glycoprotein during the transport ATPase cycle EMBO Journal. VOL 20(PART 20), 5615-5625
• SON, H S, KERR, I D and SANSOM, M S, 2000. Simulation studies on bacteriorhodopsin bundle of transmembrane alpha segments. European Biophysics Journal. 28(8), 663-73
• RANATUNGA, K M, KERR, I D, ADCOCK, C A, SMITH, G R and SANSOM, M S, 1998. Molecular dynamics of ion/channel interactions. Biochemical Society Transactions. 26(3), S301
• SANSOM, M S, KERR, I D, LAW, R, DAVISON, L and TIELEMAN, D P, 1998. Modelling the packing of transmembrane helices: application to aquaporin-1. Biochemical Society Transactions. 26(3), 509-15
• RANATUNGA, K M, KERR, I D, ADCOCK, C, SMITH, G R and SANSOM, M S, 1998. Protein-water-ion interactions in a model of the pore domain of a potassium channel: a simulation study. Biochimica et Biophysica Acta. 1370(1), 1-7
• GRICE, A L, KERR, I D and SANSOM, M S, 1997. Ion channels formed by HIV-1 Vpu: a modelling and simulation study. FEBS Letters. 405(3), 299-304
• KERR, I D and SANSOM, M S, 1997. The pore-lining region of shaker voltage-gated potassium channels: comparison of beta-barrel and alpha-helix bundle models. Biophysical Journal. 73(2), 581-602
• SANSOM, M S, KERR, I D, SMITH, G R and SON, H S, 1997. The influenza A virus M2 channel: a molecular modeling and simulation study. Virology. 233(1), 163-73
• SCHMITT, J D, SANSOM, M S, KERR, I D, LUNT, G G and EISENTHAL, R, 1997. Ferrocenoyl derivatives of alamethicin: redox-sensitive ion channels. Biochemistry. 36(5), 1115-22
• BREED, J, BIGGIN, P C, KERR, I D, SMART, O S and SANSOM, M S, 1997. Alamethicin channels - modelling via restrained molecular dynamics simulations. Biochimica et Biophysica Acta. 1325(2), 235-49
• BREED, J, KERR, I D, MOLLE, G, DUCLOHIER, H and SANSOM, M S, 1997. Ion channel stability and hydrogen bonding. Molecular modelling of channels formed by synthetic alamethicin analogues. Biochimica et Biophysica Acta. 1330(2), 103-9