Trosolwyg
Qualifications
- BSc (Honours) in Physiology and Biochemistry, Reading University, 1974
- PhD from Kings' College Hospital, London University in kidney preservation 1982
Relevant websites
- Breast Cancer (Molecular Pharmacology) Group
- Zinc-UK - an Association for scientists actively engaged in researching zinc in biology in the UK.
Funding bodies that support my research
Cyhoeddiad
2023
- Farr, G., Jones, S. and Taylor, K. M. 2023. Methods to visualise zinc transporter proteins of the SLC39A family in cells [Chapter 4]. In: Hu, J. ed. Methods in Enzymology., Vol. 687. Elsevier, pp. 67-85., (10.1016/bs.mie.2023.04.020)
- Taylor, K. M. 2023. The liv-1 subfamily of zinc transporters: from origins to present day discoveries. International Journal of Molecular Sciences 24(2), article number: 1255. (10.3390/ijms24021255)
2022
- Jones, S., Farr, G., Nimmanon, T., Ziliotto, S., Gee, J. M. and Taylor, K. M. 2022. The importance of targeting signalling mechanisms of the SLC39A family of zinc transporters to inhibit endocrine resistant breast cancer. Exploration of Targeted Anti-tumor Therapy 3, pp. 224-239. (10.37349/etat.2022.00080)
2021
- Kambe, T., Taylor, K. M. and Fu, D. 2021. Zinc transporters and their functional integration in mammalian cells. Journal of Biological Chemistry 296, article number: 100320. (10.1016/j.jbc.2021.100320)
2020
- Nimmanon, T. et al. 2020. The ZIP6/ZIP10 heteromer is essential for the zinc-mediated trigger of mitosis. Cellular and Molecular Life Sciences 78, pp. 1781-1798. (10.1007/s00018-020-03616-6)
- Suzuki, E. et al. 2020. Detailed analyses of the crucial functions of Zn transporter proteins in alkaline phosphatase activation. Journal of Biological Chemistry 295, pp. 5669-5684. (10.1074/jbc.RA120.012610)
2019
- Nimmanon, T. and Taylor, K. M. 2019. Post-translational mechanisms of zinc signalling in cancer. In: Fukada, T. and Kambe, T. eds. Zinc Signaling. Springer, Singapore, pp. 319-345., (10.1007/978-981-15-0557-7_16)
- Ziliotto, S., Gee, J. M. W., Ellis, I. O., Green, A. R., Finlay, P., Gobbato, A. and Taylor, K. M. 2019. Activated zinc transporter ZIP7 as an indicator of anti-hormone resistance in breast cancer. Metallomics 11(9), pp. 1579-1592. (10.1039/C9MT00136K)
- Mero, M., Asraf, H., Sekler, I., Taylor, K. M. and Hershfinkel, M. 2019. ZnR/GPR39 upregulation of K+/Cl−-cotransporter 3 in tamoxifen resistant breast cancer cells. Cell Calcium 81, pp. 12-20. (10.1016/j.ceca.2019.05.005)
- Ollig, J., Kloubert, V., Taylor, K. and Rink, L. 2019. B cell activation and proliferation increase intracellular zinc levels. Journal of Nutritional Biochemistry 64, pp. 72-79. (10.1016/j.jnutbio.2018.10.008)
2018
- Ventura-Bixenshpaner, H., Asraf, H., Chakraborty, M., Elkabets, M., Sekler, I., Taylor, K. M. and Hershfinkel, M. 2018. Enhanced ZnR/GPR39 activity in breast cancer, an alternative trigger of signaling leading to cell growth. Scientific Reports 8(1), article number: 8119. (10.1038/s41598-018-26459-5)
2017
- Tuncay, E., Bitirim, V. C., Durak, A., Carrat, G. R., Taylor, K., Rutter, G. A. and Turan, B. 2017. Hyperglycemia-induced changes in ZIP7 and ZnT7 expression cause Zn2+ release from the sarco(endo)plasmic reticulum and mediate ER-stress in the heart. Diabetes 66(5), pp. 1346-1358. (10.2337/db16-1099)
- Nimmanon, T., Ziliotto, S., Morris, S., Flanagan, L. and Taylor, K. M. 2017. Phosphorylation of zinc channel ZIP7 drives MAPK, PI3K and mTOR growth and proliferation signalling. Metallomics 9(5), pp. 471-481. (10.1039/C6MT00286B)
2016
- Taylor, K. M. et al. 2016. Zinc transporter ZIP10 forms a heteromer with ZIP6 which regulates embryonic development and cell migration. Biochemical Journal 473(16), pp. 2531-2544. (10.1042/BCJ20160388)
- Hessels, A. M., Taylor, K. M. and Merkx, M. 2016. Monitoring cytosolic and ER Zn2+ in stimulated breast cancer cells using genetically encoded FRET sensors. Metallomics 8, pp. 211-217. (10.1039/C5MT00257E)
2015
- Hessels, A. M., Chabosseau, P., Bakker, M. H., Engelen, W., Rutter, G. A., Taylor, K. M. and Merkx, M. 2015. eZinCh-2: a versatile, genetically encoded FRET sensor for cytosolic and intraorganelle Zn2+ imaging. ACS Chemical Biology 10(9), pp. 2126-2134. (10.1021/acschembio.5b00211)
- Liu, Y. et al. 2015. Characterization of Zinc Influx Transporters (ZIPs) in pancreatic beta cells: roles in regulating cytosolic zinc homeostasis and insulin secretion. Journal of Biological Chemistry 290, pp. 18757-18769. (10.1074/jbc.M115.640524)
- Wiggins, H. L., Wymant, J. M., Solfa, F., Hiscox, S. E., Taylor, K. M., Westwell, A. D. and Jones, A. T. 2015. Disulfiram-induced cytotoxicity and endo-lysosomal sequestration of zinc in breast cancer cells. Biochemical Pharmacology 93(3), pp. 332-342. (10.1016/j.bcp.2014.12.014)
2013
- Hogstrand, C., Kille, P., Ackland, M. L., Hiscox, S. E. and Taylor, K. M. 2013. A mechanism for epithelial–mesenchymal transition and anoikis resistance in breast cancer triggered by zinc channel ZIP6 and STAT3 (signal transducer and activator of transcription 3). Biochemical Journal 455(2), pp. 229-237. (10.1042/BJ20130483)
2012
- Taylor, K. M., Kille, P. and Hogstrand, C. 2012. Protein kinase CK2 opens the gate for zinc signaling. Cell Cycle 11(10), pp. 1863-1864. (10.4161/cc.20414)
- Taylor, K. M., Hiscox, S. E., Nicholson, R. I., Hogstrand, C. and Kille, P. 2012. Protein kinase CK2 triggers cytosolic zinc signaling pathways by phosphorylation of zinc channel ZIP7. Science Signaling 5(210), article number: ra11. (10.1126/scisignal.2002585)
2011
- Taylor, K. M., Gee, J. M. W. and Kille, P. 2011. Zinc and cancer. In: Rink, L. ed. Zinc in Human Health. Biomedical and Health Research Vol. 76. Amsterdam: IOS Press, pp. 283-304.
- Taylor, K. M., Thornton, J. K., Ford, D. and Valentine, R. A. 2011. Differential subcellular localization of the splice variants of the zinc transporter ZnT5 is dictated by the different C-terminal regions. PLoS ONE 6(8), article number: e23878. (10.1371/journal.pone.0023878)
2010
- Thomas, N. B. P., Hutcheson, I. R., Campbell, L., Gee, J. M. W., Taylor, K. M., Nicholson, R. I. and Gumbleton, M. 2010. Growth of hormone-dependent MCF-7 breast cancer cells is promoted by constitutive caveolin-1 whose expression is lost in an EGF-R-mediated manner during development of tamoxifen resistance. Breast Cancer Research and Treatment 119(3), pp. 575-591. (10.1007/s10549-009-0355-8)
- Weaver, B. P. et al. 2010. Zip4 (Slc39a4) expression is activated in hepatocellular carcinomas and functions to repress apoptosis, enhance cell cycle and increase migration. PLoS ONE 5(10), article number: e13158. (10.1371/journal.pone.0013158)
2009
- Hiscox, S. E. et al. 2009. Dual targeting of Src and ER prevents acquired antihormone resistance in breast cancer cells. Breast Cancer Research and Treatment 115(1), pp. 57-67. (10.1007/s10549-008-0058-6)
- Nicholson, R. I., Hutcheson, I. R., Hiscox, S. E., Taylor, K. M. and Gee, J. M. W. 2009. Experimental endocrine resistance: concepts and strategies. In: Hiscox, S. E., Gee, J. M. W. and Nicholson, R. I. eds. Therapeutic Resistance to Anti-Hormonal Drugs in Breast Cancer: New Molecular Aspects and their Potential. Dordrecht: Springer, pp. 1-26., (10.1007/978-1-4020-8526-0_1)
- Hogstrand, C., Kille, P., Nicholson, R. I. and Taylor, K. M. 2009. Zinc transporters and cancer: a potential role for ZIP7 as a hub for tyrosine kinase activation. Trends in Molecular Medicine 15(3), pp. 101-111. (10.1016/j.molmed.2009.01.004)
- Ma, X. L. et al. 2009. Identification of LIV1, a Putative Zinc Transporter Gene Responsible for HDACi-Induced Apoptosis, Using a Functional Gene Screen Approach. Molecular Cancer Therapeutics 8(11), pp. 3108-3116. (10.1158/1535-7163.mct-08-0772)
2008
- Taylor, K. M., Vichova, P., Jordan, N. J., Hiscox, S. E., Hendley, R. and Nicholson, R. I. 2008. ZIP7-mediated intracellular zinc transport contributes to aberrant growth factor signaling in antihormone-resistant breast cancer cells. Endocrinology 149(10), pp. 4912-4920. (10.1210/en.2008-0351)
- Nicholson, R. I., Hutcheson, I. R., Jones, H. E., Taylor, K. M., Hiscox, S. E. and Gee, J. M. W. 2008. Compensatory signalling induced by anti-hormone and anti-growth factor therapies in breast cancer: a starting point for the development of resistance to targeted therapies.. In: Pasqualini, J. R. ed. Breast cancer: prognosis, treatment and prevention. 2nd ed. London: Informa Healthcare, pp. 123-136.
- Taylor, K. M. 2008. A distinct role in breast cancer for two LIV-1 family zinc transporters. Biochemical Society Transactions 36(6), pp. 1247-1251. (10.1042/bst0361247)
- Taylor, K. M., Jordan, N. J., Hiscox, S. E., Gee, J. M. W. and Nicholson, R. I. 2008. Zinc transporter HKE4 as a new target in antihormone resistance of breast cancer [Abstract]. Breast Cancer Research 10(s2), article number: P42. (10.1186/bcr1926)
- Zahari, N. M., Taylor, K. M. and Nicholson, R. I. 2008. Functional evaluation of members of the LIV-1 family of proteins and their role in breast cancer. EJC Supplements 6(12), pp. 184-184.
2007
- Taylor, K. M. et al. 2007. The emerging role of the LIV-1 subfamily of zinc transporters in breast cancer. Molecular Medicine 13(7-8), pp. 396-406.
- Zhao, L., Chen, W., Taylor, K. M., Cai, B. and Li, X. 2007. LIV-1 suppression inhibits HeLa cell invasion by targeting ERK1/2-Snail/Slug pathway. Biochemical and Biophysical Research Communications 363(1), pp. 82-88. (10.1016/j.bbrc.2007.08.127)
- Nicholson, R. I., Hutcheson, I. R., Jones, H. E., Hiscox, S. E., Giles, M., Taylor, K. M. and Gee, J. M. W. 2007. Growth factor signalling in endocrine and anti-growth factor resistant breast cancer. Reviews in Endocrine and Metabolic Disorders 8(3), pp. 241-253. (10.1007/s11154-007-9033-5)
2006
- Hiscox, S. E. et al. 2006. Tamoxifen-resistance in MCF7 cells promotes EMT-like behaviour and involves modulation of [beta]-catenin phosphorylation. International journal of cancer 118(2), pp. 290-301. (10.1002/ijc.21355)
2005
- Jones, H. E., Gee, J. M. W., Taylor, K. M., Barrow, D., Williams, H. D., Rubini, M. and Nicholson, R. I. 2005. Development of strategies for the use of anti-growth factor treatments. Endocrine-Related Cancer 12(S1), pp. S173-S182. (10.1677/erc.1.01004)
- Taylor, K. M., Vichova, P., Hiscox, S. E. and Nicholson, R. 2005. Zinc-dependant stimulation of Src, EGFR and IGFR signalling pathways in tamoxifen-resistant breast cancer and the role of zinc transporters. Breast Cancer Research and Treatment 94(Supp 1), pp. S162-S162.
2004
- Taylor, K. M., Hiscox, S. E. and Nicholson, R. 2004. Zinc transporter LIV-1: a link between cellular development and cancer progression. Trends in Endocrinology and Metabolism 15(10), pp. 461-463.
- Taylor, K. M., Johnson, A., Morgan, H. E. and Nicholson, R. I. 2004. Structure-function analysis of HKE4, a member of the new LIV-1 subfamily of zinc transporters. Biochemical Journal 377(1), pp. 131-139. (10.1042/BJ20031183)
2003
- Taylor, K. M., Hadley, L. J., Johnson, A., Morgan, H. E. and Nicholson, R. I. 2003. Structure-function analysis of LIV-1, the breast cancer-associated protein that belongs to a new subfamily of zinc transporters. Biochemical Journal 375(1), pp. 51-59. (10.1042/BJ20030478)
2001
- Glynne-Jones, E. M. et al. 2001. TENB2, a proteoglycan identified in prostate cancer that is associated with disease progression and androgen independence. International Journal of Cancer 94(2), pp. 178-184. (10.1002/ijc.1450)
2000
- Dunstan, S. L., Sala-Newby, G. B., Fajardo, A. B., Taylor, K. M. and Campbell, A. K. 2000. Cloning and expression of the bioluminescent photoprotein pholasin from the bivalve mollusc Pholas dactylus. Journal of Biological Chemistry 275(13), pp. 9403-9409. (10.1074/jbc.275.13.9403)
1998
- Sala-Newby, G. B., Taylor, K. M., Badminton, M. N., Rembold, C. M. and Campbell, A. K. 1998. Imaging bioluminescent indicators shows Ca2+ and ATP permeability thresholds in live cells attacked by complement. Immunology 93(4), pp. 601-609. (10.1046/j.1365-2567.1998.00004.x)
1997
- Taylor, K. M., Trimby, A. R. and Campbell, A. K. 1997. Mutation of recombinant complement component C9 reveals the significance of the N-terminal region for polymerization. Immunology 91(1), pp. 20-27. (10.1046/j.1365-2567.1997.00225.x)
1994
- Taylor, K. M., Morgan, B. P. and Campbell, A. K. 1994. Altered glycosylation and selected mutation in recombinant human complement component C9: effects on haemolytic activity. Immunology 83(3), pp. 501-506.
- Taylor, K. M., Luzio, J. P. and Campbell, A. K. 1994. A method for in vitro synthesis of unglycosylated recombinant complement component C9. Journal of Immunological Methods 167(1-2), pp. 129-137. (10.1016/0022-1759(94)90082-5)
Adrannau llyfrau
- Farr, G., Jones, S. and Taylor, K. M. 2023. Methods to visualise zinc transporter proteins of the SLC39A family in cells [Chapter 4]. In: Hu, J. ed. Methods in Enzymology., Vol. 687. Elsevier, pp. 67-85., (10.1016/bs.mie.2023.04.020)
- Nimmanon, T. and Taylor, K. M. 2019. Post-translational mechanisms of zinc signalling in cancer. In: Fukada, T. and Kambe, T. eds. Zinc Signaling. Springer, Singapore, pp. 319-345., (10.1007/978-981-15-0557-7_16)
- Taylor, K. M., Gee, J. M. W. and Kille, P. 2011. Zinc and cancer. In: Rink, L. ed. Zinc in Human Health. Biomedical and Health Research Vol. 76. Amsterdam: IOS Press, pp. 283-304.
- Nicholson, R. I., Hutcheson, I. R., Hiscox, S. E., Taylor, K. M. and Gee, J. M. W. 2009. Experimental endocrine resistance: concepts and strategies. In: Hiscox, S. E., Gee, J. M. W. and Nicholson, R. I. eds. Therapeutic Resistance to Anti-Hormonal Drugs in Breast Cancer: New Molecular Aspects and their Potential. Dordrecht: Springer, pp. 1-26., (10.1007/978-1-4020-8526-0_1)
- Nicholson, R. I., Hutcheson, I. R., Jones, H. E., Taylor, K. M., Hiscox, S. E. and Gee, J. M. W. 2008. Compensatory signalling induced by anti-hormone and anti-growth factor therapies in breast cancer: a starting point for the development of resistance to targeted therapies.. In: Pasqualini, J. R. ed. Breast cancer: prognosis, treatment and prevention. 2nd ed. London: Informa Healthcare, pp. 123-136.
Erthyglau
- Taylor, K. M. 2023. The liv-1 subfamily of zinc transporters: from origins to present day discoveries. International Journal of Molecular Sciences 24(2), article number: 1255. (10.3390/ijms24021255)
- Jones, S., Farr, G., Nimmanon, T., Ziliotto, S., Gee, J. M. and Taylor, K. M. 2022. The importance of targeting signalling mechanisms of the SLC39A family of zinc transporters to inhibit endocrine resistant breast cancer. Exploration of Targeted Anti-tumor Therapy 3, pp. 224-239. (10.37349/etat.2022.00080)
- Kambe, T., Taylor, K. M. and Fu, D. 2021. Zinc transporters and their functional integration in mammalian cells. Journal of Biological Chemistry 296, article number: 100320. (10.1016/j.jbc.2021.100320)
- Nimmanon, T. et al. 2020. The ZIP6/ZIP10 heteromer is essential for the zinc-mediated trigger of mitosis. Cellular and Molecular Life Sciences 78, pp. 1781-1798. (10.1007/s00018-020-03616-6)
- Suzuki, E. et al. 2020. Detailed analyses of the crucial functions of Zn transporter proteins in alkaline phosphatase activation. Journal of Biological Chemistry 295, pp. 5669-5684. (10.1074/jbc.RA120.012610)
- Ziliotto, S., Gee, J. M. W., Ellis, I. O., Green, A. R., Finlay, P., Gobbato, A. and Taylor, K. M. 2019. Activated zinc transporter ZIP7 as an indicator of anti-hormone resistance in breast cancer. Metallomics 11(9), pp. 1579-1592. (10.1039/C9MT00136K)
- Mero, M., Asraf, H., Sekler, I., Taylor, K. M. and Hershfinkel, M. 2019. ZnR/GPR39 upregulation of K+/Cl−-cotransporter 3 in tamoxifen resistant breast cancer cells. Cell Calcium 81, pp. 12-20. (10.1016/j.ceca.2019.05.005)
- Ollig, J., Kloubert, V., Taylor, K. and Rink, L. 2019. B cell activation and proliferation increase intracellular zinc levels. Journal of Nutritional Biochemistry 64, pp. 72-79. (10.1016/j.jnutbio.2018.10.008)
- Ventura-Bixenshpaner, H., Asraf, H., Chakraborty, M., Elkabets, M., Sekler, I., Taylor, K. M. and Hershfinkel, M. 2018. Enhanced ZnR/GPR39 activity in breast cancer, an alternative trigger of signaling leading to cell growth. Scientific Reports 8(1), article number: 8119. (10.1038/s41598-018-26459-5)
- Tuncay, E., Bitirim, V. C., Durak, A., Carrat, G. R., Taylor, K., Rutter, G. A. and Turan, B. 2017. Hyperglycemia-induced changes in ZIP7 and ZnT7 expression cause Zn2+ release from the sarco(endo)plasmic reticulum and mediate ER-stress in the heart. Diabetes 66(5), pp. 1346-1358. (10.2337/db16-1099)
- Nimmanon, T., Ziliotto, S., Morris, S., Flanagan, L. and Taylor, K. M. 2017. Phosphorylation of zinc channel ZIP7 drives MAPK, PI3K and mTOR growth and proliferation signalling. Metallomics 9(5), pp. 471-481. (10.1039/C6MT00286B)
- Taylor, K. M. et al. 2016. Zinc transporter ZIP10 forms a heteromer with ZIP6 which regulates embryonic development and cell migration. Biochemical Journal 473(16), pp. 2531-2544. (10.1042/BCJ20160388)
- Hessels, A. M., Taylor, K. M. and Merkx, M. 2016. Monitoring cytosolic and ER Zn2+ in stimulated breast cancer cells using genetically encoded FRET sensors. Metallomics 8, pp. 211-217. (10.1039/C5MT00257E)
- Hessels, A. M., Chabosseau, P., Bakker, M. H., Engelen, W., Rutter, G. A., Taylor, K. M. and Merkx, M. 2015. eZinCh-2: a versatile, genetically encoded FRET sensor for cytosolic and intraorganelle Zn2+ imaging. ACS Chemical Biology 10(9), pp. 2126-2134. (10.1021/acschembio.5b00211)
- Liu, Y. et al. 2015. Characterization of Zinc Influx Transporters (ZIPs) in pancreatic beta cells: roles in regulating cytosolic zinc homeostasis and insulin secretion. Journal of Biological Chemistry 290, pp. 18757-18769. (10.1074/jbc.M115.640524)
- Wiggins, H. L., Wymant, J. M., Solfa, F., Hiscox, S. E., Taylor, K. M., Westwell, A. D. and Jones, A. T. 2015. Disulfiram-induced cytotoxicity and endo-lysosomal sequestration of zinc in breast cancer cells. Biochemical Pharmacology 93(3), pp. 332-342. (10.1016/j.bcp.2014.12.014)
- Hogstrand, C., Kille, P., Ackland, M. L., Hiscox, S. E. and Taylor, K. M. 2013. A mechanism for epithelial–mesenchymal transition and anoikis resistance in breast cancer triggered by zinc channel ZIP6 and STAT3 (signal transducer and activator of transcription 3). Biochemical Journal 455(2), pp. 229-237. (10.1042/BJ20130483)
- Taylor, K. M., Kille, P. and Hogstrand, C. 2012. Protein kinase CK2 opens the gate for zinc signaling. Cell Cycle 11(10), pp. 1863-1864. (10.4161/cc.20414)
- Taylor, K. M., Hiscox, S. E., Nicholson, R. I., Hogstrand, C. and Kille, P. 2012. Protein kinase CK2 triggers cytosolic zinc signaling pathways by phosphorylation of zinc channel ZIP7. Science Signaling 5(210), article number: ra11. (10.1126/scisignal.2002585)
- Taylor, K. M., Thornton, J. K., Ford, D. and Valentine, R. A. 2011. Differential subcellular localization of the splice variants of the zinc transporter ZnT5 is dictated by the different C-terminal regions. PLoS ONE 6(8), article number: e23878. (10.1371/journal.pone.0023878)
- Thomas, N. B. P., Hutcheson, I. R., Campbell, L., Gee, J. M. W., Taylor, K. M., Nicholson, R. I. and Gumbleton, M. 2010. Growth of hormone-dependent MCF-7 breast cancer cells is promoted by constitutive caveolin-1 whose expression is lost in an EGF-R-mediated manner during development of tamoxifen resistance. Breast Cancer Research and Treatment 119(3), pp. 575-591. (10.1007/s10549-009-0355-8)
- Weaver, B. P. et al. 2010. Zip4 (Slc39a4) expression is activated in hepatocellular carcinomas and functions to repress apoptosis, enhance cell cycle and increase migration. PLoS ONE 5(10), article number: e13158. (10.1371/journal.pone.0013158)
- Hiscox, S. E. et al. 2009. Dual targeting of Src and ER prevents acquired antihormone resistance in breast cancer cells. Breast Cancer Research and Treatment 115(1), pp. 57-67. (10.1007/s10549-008-0058-6)
- Hogstrand, C., Kille, P., Nicholson, R. I. and Taylor, K. M. 2009. Zinc transporters and cancer: a potential role for ZIP7 as a hub for tyrosine kinase activation. Trends in Molecular Medicine 15(3), pp. 101-111. (10.1016/j.molmed.2009.01.004)
- Ma, X. L. et al. 2009. Identification of LIV1, a Putative Zinc Transporter Gene Responsible for HDACi-Induced Apoptosis, Using a Functional Gene Screen Approach. Molecular Cancer Therapeutics 8(11), pp. 3108-3116. (10.1158/1535-7163.mct-08-0772)
- Taylor, K. M., Vichova, P., Jordan, N. J., Hiscox, S. E., Hendley, R. and Nicholson, R. I. 2008. ZIP7-mediated intracellular zinc transport contributes to aberrant growth factor signaling in antihormone-resistant breast cancer cells. Endocrinology 149(10), pp. 4912-4920. (10.1210/en.2008-0351)
- Taylor, K. M. 2008. A distinct role in breast cancer for two LIV-1 family zinc transporters. Biochemical Society Transactions 36(6), pp. 1247-1251. (10.1042/bst0361247)
- Taylor, K. M., Jordan, N. J., Hiscox, S. E., Gee, J. M. W. and Nicholson, R. I. 2008. Zinc transporter HKE4 as a new target in antihormone resistance of breast cancer [Abstract]. Breast Cancer Research 10(s2), article number: P42. (10.1186/bcr1926)
- Zahari, N. M., Taylor, K. M. and Nicholson, R. I. 2008. Functional evaluation of members of the LIV-1 family of proteins and their role in breast cancer. EJC Supplements 6(12), pp. 184-184.
- Taylor, K. M. et al. 2007. The emerging role of the LIV-1 subfamily of zinc transporters in breast cancer. Molecular Medicine 13(7-8), pp. 396-406.
- Zhao, L., Chen, W., Taylor, K. M., Cai, B. and Li, X. 2007. LIV-1 suppression inhibits HeLa cell invasion by targeting ERK1/2-Snail/Slug pathway. Biochemical and Biophysical Research Communications 363(1), pp. 82-88. (10.1016/j.bbrc.2007.08.127)
- Nicholson, R. I., Hutcheson, I. R., Jones, H. E., Hiscox, S. E., Giles, M., Taylor, K. M. and Gee, J. M. W. 2007. Growth factor signalling in endocrine and anti-growth factor resistant breast cancer. Reviews in Endocrine and Metabolic Disorders 8(3), pp. 241-253. (10.1007/s11154-007-9033-5)
- Hiscox, S. E. et al. 2006. Tamoxifen-resistance in MCF7 cells promotes EMT-like behaviour and involves modulation of [beta]-catenin phosphorylation. International journal of cancer 118(2), pp. 290-301. (10.1002/ijc.21355)
- Jones, H. E., Gee, J. M. W., Taylor, K. M., Barrow, D., Williams, H. D., Rubini, M. and Nicholson, R. I. 2005. Development of strategies for the use of anti-growth factor treatments. Endocrine-Related Cancer 12(S1), pp. S173-S182. (10.1677/erc.1.01004)
- Taylor, K. M., Vichova, P., Hiscox, S. E. and Nicholson, R. 2005. Zinc-dependant stimulation of Src, EGFR and IGFR signalling pathways in tamoxifen-resistant breast cancer and the role of zinc transporters. Breast Cancer Research and Treatment 94(Supp 1), pp. S162-S162.
- Taylor, K. M., Hiscox, S. E. and Nicholson, R. 2004. Zinc transporter LIV-1: a link between cellular development and cancer progression. Trends in Endocrinology and Metabolism 15(10), pp. 461-463.
- Taylor, K. M., Johnson, A., Morgan, H. E. and Nicholson, R. I. 2004. Structure-function analysis of HKE4, a member of the new LIV-1 subfamily of zinc transporters. Biochemical Journal 377(1), pp. 131-139. (10.1042/BJ20031183)
- Taylor, K. M., Hadley, L. J., Johnson, A., Morgan, H. E. and Nicholson, R. I. 2003. Structure-function analysis of LIV-1, the breast cancer-associated protein that belongs to a new subfamily of zinc transporters. Biochemical Journal 375(1), pp. 51-59. (10.1042/BJ20030478)
- Glynne-Jones, E. M. et al. 2001. TENB2, a proteoglycan identified in prostate cancer that is associated with disease progression and androgen independence. International Journal of Cancer 94(2), pp. 178-184. (10.1002/ijc.1450)
- Dunstan, S. L., Sala-Newby, G. B., Fajardo, A. B., Taylor, K. M. and Campbell, A. K. 2000. Cloning and expression of the bioluminescent photoprotein pholasin from the bivalve mollusc Pholas dactylus. Journal of Biological Chemistry 275(13), pp. 9403-9409. (10.1074/jbc.275.13.9403)
- Sala-Newby, G. B., Taylor, K. M., Badminton, M. N., Rembold, C. M. and Campbell, A. K. 1998. Imaging bioluminescent indicators shows Ca2+ and ATP permeability thresholds in live cells attacked by complement. Immunology 93(4), pp. 601-609. (10.1046/j.1365-2567.1998.00004.x)
- Taylor, K. M., Trimby, A. R. and Campbell, A. K. 1997. Mutation of recombinant complement component C9 reveals the significance of the N-terminal region for polymerization. Immunology 91(1), pp. 20-27. (10.1046/j.1365-2567.1997.00225.x)
- Taylor, K. M., Morgan, B. P. and Campbell, A. K. 1994. Altered glycosylation and selected mutation in recombinant human complement component C9: effects on haemolytic activity. Immunology 83(3), pp. 501-506.
- Taylor, K. M., Luzio, J. P. and Campbell, A. K. 1994. A method for in vitro synthesis of unglycosylated recombinant complement component C9. Journal of Immunological Methods 167(1-2), pp. 129-137. (10.1016/0022-1759(94)90082-5)
Ymchwil
Aelod o Ddisgyblaeth Ymchwil Ffarmacoleg a Ffisioleg yr Ysgol.
Diddordebau ymchwil
- Mecanwaith gweithredu cludwyr sinc
- Rheoleiddio homeostasis sinc mewngellog
- Rôl cludwyr sinc mewn mudo celloedd
- Rôl cludwyr sinc a sinc mewn dilyniant canser
- Rôl cludwyr sinc wrth gychwyn rhaniad celloedd
Fy mhrif ffocws yw ymchwilio i fecanwaith gweithredu cludwyr sinc cellog, yn enwedig y teulu ZIP (a elwir hefyd yn SLC39A). Y bwriad yw cadarnhau model ar gyfer signalau sinc integredig mewn celloedd, gan gadarnhau rôl allweddol cludwyr sinc, yn enwedig ZIP7, a chysylltu'r canfyddiadau ag effeithiau biolegol sylfaenol sinc cellog. Credir bod y digwyddiadau signalau sinc hyn yn cael eu rheoli'n bennaf gan gludwyr neu sianeli sinc penodol a bydd fy nofel ddiweddar yn canfod y gellir rheoli eu gallu i gludo sinc trwy ffosfforeiddio, mecanwaith na welwyd ei debyg o'r blaen ar gyfer cludwyr sinc, am berthynas strwythurol uniongyrchol a/neu swyddogaethol â llwybrau signalau cellog. Mae'r digwyddiadau hyn yn arwain at effeithiau cellog amrywiol ar brosesau arferol megis twf, datblygiad a mudo neu, pan gaiff eu rheoleiddio yn aberrant, clefydau fel canser, diabetes a niwroddirywiol gan sicrhau bod y prosiect hwn yn cael ei gymhwyso'n eang ar gyfer cyflyrau arferol a chlefydau.
Prif ffocws fy ymchwil yw deall sut mae cludwyr sinc yn gweithio mewn celloedd i reoli homeostasis sinc mewngellog. Mae gen i ddiddordeb arbennig yn y 9 aelod dynol o deulu LIV-1 o gludwyr sinc a'u rôl yn natblygiad canser y fron. Mae'r astudiaethau hyn yn cynnwys effeithiau sinc ar lwybrau signalau lluosog yn ogystal â thwf a goresgyniad, pob elfen y gwyddys ei bod yn arwain at gynnydd canser. Gellir acheieved hyn trwy ddefnyddio araeau ffosffo-kinase ar y cyd â mutagenesis a gyfeiriwyd gan y safle o gludwyr sinc.
Trin sinc mewn celloedd
Mae dau deulu o gludwyr sinc yn galluogi sinc i groesi pilenni biolegol: Teulu ZnT o gludwyr efflux sinc (a elwir SLC30A) a theulu ZIP cludwyr mewnlifiad sinc (a elwir SLC39A). Mae'r teulu ZIP o gludwyr sinc sinc yn cynhyrchu sinc cytosol labordy ac o'r herwydd dangoswyd bod ganddynt rolau biolegol eang mewn cyflyrau arferol a chlefydau. Mae cludydd sinc ZIP7, unigryw ymhlith cludwyr ZIP, wedi'i leoli ar bilen ER ac yn ddiweddar rydym wedi cynnig rôl reoli ar gyfer ZIP7 wrth ryddhau sinc o siopau mewngellol gan arwain at actifadu kinases tyrosine lluosog trwy anweithgarwch wedi'i gyfryngu â sinc o phosphatases protein. Rydym wedi dangos bod ZIP7 yn gofyn am phopshorylation cyn y gall gludo sinc a gweithredu fel canolbwynt i'w ryddhau o siopau.
Mecanwaith gweithredu teulu LIV-1 o gludwyr sinc
Gan ddefnyddio meddalwedd gyfrifiadurol i gymharu dilyniannau protein, roeddwn yn gallu dangos bod LIV-1 yn perthyn i deulu newydd o gludwyr mewnlifiad sinc sy'n gyfanswm o naw aelod o'r teulu dynol. Rhagwelodd chwiliadau cyfrifiadurol o strwythur eilaidd fod y moleciwlau hyn yn cynnwys parthau trawsbilen 8, N-terminus allgellog hir, C-terminus allgellog byr, dilyniant consensws ar gyfer y teulu ZIP o gludwyr sinc a dilyniant consensws ar gyfer safle rhwymo sinc catalytig metalloproteases, (HEXXH, lle mae H = histidine, E = asid glutamig ac X = unrhyw asid amino). Roedd y motiff olaf hwn yn anarferol gan ei fod hefyd yn cynnwys dau weddillion nofel (HEX PH E), proline (P) ac asid glutamig (E), na welwyd ei debyg o'r blaen yn y swyddi hyn mewn unrhyw motiffau metalloprotease eraill. Gan chwilio cronfa ddata NCBI nad yw'n ddi-waith gan ddefnyddio BLAST a motiff unigryw HEXPHEXGD o LIV-1, rydym wedi nodi dros 39 o ddilyniannau o 12 rhywogaeth, gan gynnwys dynol, llygoden, C.elegans, Drosophila, burum a bacteria, sy'n cynnwys y motiff unigryw a hynod warchodedig hwn. Mae'r teulu hwn bellach wedi cael ei alw'n SLC39A. Mae aelodau'r is-deulu LIV-1 yn debyg i gludwyr superfamily ZIP mewn strwythur eilaidd a'r gallu i gludo ïonau metel ar draws y bilen plasma neu'r pilenni mewngellol. Mae lleoleiddio rhai aelodau o'r teulu i lamellipodiae yn adlewyrchu lleoliad cellog y metalloproteases matrics math bilen. Gall y gwahaniaethau hyn i gludwyr sinc eraill fod yn gyson â rôl amgen iddynt mewn celloedd, yn enwedig mewn clefydau fel canser.
Rôl cludwyr sinc mewn iechyd a chlefydau
Mae'r 9 aelod dynol o deulu LIV-1 o gludwyr sinc yn cael eu cysylltu'n gynyddol mewn amrywiaeth o gyflyrau clefydau, yn enwedig niwroddirywio, asthma, canser y prostad a chanser y fron. Mae ymchwilio i sut y gall lleoleiddio cellog a phenodol meinwe y cludwyr sinc hyn newid homeostasis sinc yn hollbwysig i ddeall union rôl y cludwyr hyn yn y gwahanol gyflyrau clefyd hyn.
Rôl cludwyr sinc mewn mudo celloedd a mitosis
Mae ZIP6 (neu LIV-1 fel yr oedd yn arfer cael ei adnabod) yn genyn a reoleiddir gan estrogen sydd wedi'i gysylltu â chanser metastatig y fron. Mae ei ganfod wedi bod yn gysylltiedig â chanser y fron positif derbynnydd estrogen ac â lledaeniad metastatig y canserau hyn i'r nodau lymff rhanbarthol. Rydym wedi dangos rôl ar gyfer ZIP6 a ZIP10 wrth hyrwyddo mudo celloedd ac rydym bellach wedi ymestyn hyn i ddeall y rôl y maent yn ei chwarae wrth gychwyn mitosis. Mae'r darganfyddiad hwn wedi galluogi ymchwil gan ddefnyddio gwrthgyrff ZIP unigryw i atal neu arafu twf canser.
Rôl cludwyr sinc a sinc mewn canser y fron
Rydym wedi gweld lefel uwch o sinc mewngellog yn ein model 'mewnol' o ganser y fron sy'n gwrthsefyll tamoxifen. Mae hyn wedi cychwyn ymchwiliad i rôl bosibl ar gyfer sinc wrth actifadu llwybrau signalau a welwyd yn y celloedd hyn yn ogystal ag yn y cynnydd mewn ymddygiad ymosodol a welwyd yn y celloedd hyn. Trwy'r invetsigation hwn rydym wedi dangos rôl bwysig i'r cludwr sinc ZIP7 wrth yrru twf ac actifadu canserau'r fron sy'n gwrthsefyll tamoxifen. Mae ein darganfyddiad bod ZIP7 yn gofyn am ffosfforyleiddiad cyn y gall ryddhau sinc o siopau wedi ein galluogi i gynhyrchu gwrthgorff ffosffo-ZIP7 unigryw sydd ond yn adnabod ZIP7 pan fydd yn rhyddhau sinc o siopau. Mae gan y gwrthgorff hwn lawer o botensial ar gyfer defnydd clinigol gan fod ei weithgaredd yn cyd-fynd â thwf celloedd cynyddol ac amlhau.
Y darganfyddiad bod ZIP6 a ZIP10 yn cychwyn rhaniad celloedd
Mae ZIP6 a ZIP10 bob amser wedi bod yn anodd eu hastudio oherwydd eu lefel uchel o reoleiddio mewn celloedd. Fodd bynnag, rydym bellach wedi darganfod y rheswm dros hyn. Mae ZIP6 a ZIP10 yn ffurfio cyfadeilad sy'n symud i'r gell pan fydd y gell yn barod i gael ei rhannu â chelloedd. Mae'r cymhleth hwn yn dod â sinc i mewn i'r gell a bod gan sinc swyddogaeth arbenigol iawn i sbarduno llwybrau arferol mitosis. Heb y mewnlifiad sinc hwn, nid yw rhaniad celloedd yn digwydd. Rydym bellach wedi ehangu ar y canlyniad hwn ac wedi cynhyrchu rhai gwrthgyrff newydd a all atal mewnlifiad sinc ac felly atal rhaniad celloedd sydd bellach yn cael eu harchwilio fel triniaeth canser newydd.
Cydweithredwyr
Prifysgol Caerdydd
- Dr Julia Gee, Ysgol Fferylliaeth a Gwyddorau Fferyllol, Prifysgol Caerdydd
- Yr Athro Richard Clarkson, Ysgol y Biowyddorau, Prifysgol Caerdydd
DU
- Yr Athro Christer Hogstrand, Coleg y Brenin, Llundain
- Yr Athro Wolfgang Maret, Coleg y Brenin, Llundain
- Yr Athro Iain Ellis, Gwyddorau Meddygol Moleciwlaidd, City Hospital, Nottingham: cydweithio ar gyfres canser y fron glinigol
- Yr Athro John Robertson, Ysbyty'r Ddinas, Nottingham: cydweithio ar gyfres canser y fron glinigol
Rhyngwladol
- Yr Athro Glen Andrews, Adran Biocemeg a Bioleg Foleciwlaidd, Canolfan Feddygol Prifysgol Kansas, UDA
- Yr Athro Michal Hershfinkel, Israel
- Yr Athro Lothar Rink, Aachen, Yr Almaen
- Yr Athro Gerold Schmitt-Ulms, Toronto, Canada
Technolegau a ddefnyddir
- Mae peirianneg yn adeiladu ar gyfer mynegi proteinau cyfunol mewn celloedd mamalaidd gan ddefnyddio clonio TOPO-TA a PCR.
- Knockdown o fynegiant protein gan ddefnyddio siRNA
- Cynhyrchu mutants gan ddefnyddio mutagenesis a dilyniannu genynnau a gyfeirir ar y safle i alluogi ymchwilio i weddillion allweddol yng ngweithgaredd swyddogaethol gwahanol foleciwlau
- Defnyddio tagiau ar gyfer monitro mynegiant o broteinau cyfunol mewn celloedd
- Defnyddio llinellau celloedd knockout a gynhyrchir gan ddefnyddio technoleg crispr
- Microsgopeg fflwroleuol a chonfocal o chwiliedydd lluosog mewn celloedd byw a sefydlog
- Assay Ligation Agosrwydd
- Dadansoddiad arae phospho-kinase
- Monitro amser real o grynodiadau Zn2+ mewn celloedd gan ddefnyddio gwahanol ddangosyddion sinc penodol fel Casnewydd Green, Fluozin-3 a Zinquin.
- Dylunio a chynhyrchu gwrthgyrff newydd i broteinau cludo sinc
- SDS-PAGE, Western Blotting, dadansoddiad FACS, immunocytochemistry.
- Defnyddio meddalwedd cyfrifiadurol i ragfynegi swyddogaeth protein
- Defnyddio cronfeydd data canser i ymchwilio i rôl cludwyr sinc
Addysgu
- Supervision of undergraduate research projects
- Supervision of postgraduate students
Bywgraffiad
Proffil gyrfa
Astudiodd Kathryn Taylor am PhD ym maes cadwraeth aren ar gyfer trawsblannu yn yr adran lawdriniaeth yn Ysbyty Coleg y Brenin, Denmark Hill, Llundain.
Ar ôl seibiant gyrfaol 9 mlynedd dychwelodd i ymchwilio i rôl cydran ategu C9 mewn arthritis yn yr adran Biocemeg Feddygol, Ysbyty Heath, Caerdydd.
Ymunodd Kathryn â Chanolfan Ymchwil Canser Tenovus ym 1997 lle mae hi wedi bod yn ymchwilio i rôl y teulu LIV-1 o gludwyr sinc mewn canser y fron.
Symudodd Kathryn i'r Ysgol Fferylliaeth a'r Gwyddorau Fferyllol gydag Uned Tenovus yn 2000 ac mae'n dal i fod wedi'i lleoli yno.
Dyfarnwyd cymrodoriaeth Univeristy Ymddiriedolaeth Wellcome i Kathryn o 2010-2015 a helpodd i gadarnhau ei diddordeb mewn cludo sinc, yn enwedig ZIP7, ZIP6 a ZIP10.
Yn 2015, cyflogwyd Kathryn fel Uwch-ddarlithydd yn yr Ysgol Fferylliaeth a Gwyddorau Fferyllol, lle dechreuodd ddysgu ar yr MSc mewn Bioleg a Therapiwteg Celloedd Canser.
Anrhydeddau a dyfarniadau
- Gwobr Fredericksen am ragoriaeth mewn bioleg sinc gan y Gymdeithas Ryngwladol ar gyfer Bioleg Zinc yn 2022
- Etholwyd yn gyn-lywydd y Gymdeithas Ryngwladol ar gyfer Bioleg Sinc (ISZB) 2019-2021
- Llywydd y Gymdeithas Ryngwladol ar gyfer Bioleg Sinc (ISZB) 2017-2019
- Aelod o Fwrdd Cymdeithas Ryngwladol Bioleg Sinc (ISZB) 2013-2017
Aelodaethau proffesiynol
- An invited member of the editorial advisory panel of the Biochemistry Journal since 2004
- A member of Cardiff University Genetic Modification Safety Committee since 2002
Pwyllgorau ac adolygu
Adolygydd Journal and Grant ar gyfer sawl cyfnodolyn
Meysydd goruchwyliaeth
Goruchwyliaeth gyfredol
Georgia Farr
Myfyriwr ymchwil
Ahmed Alzahrani
Myfyriwr ymchwil
Contact Details
+44 29208 75292
Adeilad Redwood , Llawr 2, Ystafell 2.47, Rhodfa'r Brenin Edward VII, Caerdydd, CF10 3NB
Themâu ymchwil
Arbenigeddau
- Cludwyr sinc
- Oncoleg a charsinogenesis
- Mitosis