University of Dundee

Professor Inke Nathke

From molecules to tissue architecture
Position: 
Professor of Epithelial Biology and Cancer, Interim Dean of the School of Life Sciences and Associate Dean for Professional Culture
Address: 
School of Life Sciences, University of Dundee, Dundee
Full Telephone: 
+44 (0) 1382 385821, int ext 85821
Email: 

Research

This Figure shows a PTK cell in early mitosis stained for APC protein (red), the Morphogenesis in development and tissue maintenance requires an intricate balance between cell-cell interactions, cell-proliferation, cell migration and differentiation. Loss of the co-ordination between these processes prohibits proper development and is also involved in tumour formation. The long-term goal of research in my laboratory is to understand how cellular adhesion, migration, and cell division are regulated in concert during development and differentiation and how changes in these processes contribute to tumour formation.

The image shows whole mount mouse intestinal tissue that was stained with phallo My particular focus is the adenomatous polyposis coli protein, a large cytoplasmic protein that has been implicated in a variety of basic cellular processes including cell migration, cell adhesion, and proliferation. APC binds to beta-catenin and regulates its intracellular concentration. Beta-catenin is an important mediator of cell adhesion and also plays a role in regulating the activity of specific transcription factors. APC also interacts directly and indirectly with cytoskeletal proteins and regulates their stability. Its multi-functional nature places APC at the interface between regulation of cellular architecture and differentiation programs and this may explain the high penetrance of APC mutations, particularly in the intestinal tract: APC mutations constitute an extremely early stage of inherited as well as sporadic colon cancer. In addition, patients with somatic deletions in one of the APC alleles, have an increased risk for developing brain tumours and other epithelial abnormalities.

The aim of work in my laboratory is to determine the molecular mechanisms that govern the role of the APC protein in cell migration, adhesion and division and includes investigating the relationship between different protein interactions of APC in vivo. The experimental approaches we use include whole tissue, cultured cells, in vitro assays combined with cellular and molecular biology techniques as well as high-resolution fluorescence microscopy.

Publications

Chen. Y., Vandereyken, M., Newton, IP., Moraga, I., Näthke, I.S., Swamy, M (2019) Loss of adenomatous polyposis coli function renders intestinal epithelial cells resistant to the cytokine IL-22.  doi/10.1371/journal.pbio.3000540 PMCID 6903767 PMID 31770366  Read Article

Popow, O., Paulo, J. A., Tatham, M., Volk, M., Rojas-Fernandez, A., Loyer, N., Newton, I., Januschke, J., Haigis, K. M., Näthke, I. (2019) Identification of endogenous Adenomatous polyposis coli interaction partners and b-catenin-independent targets by proteomics.  Molecular Cancer Research 17(9) 1828-1841 doi.org/10.1158/1541-7786.MCR-18-1154  PMID 31160382  Read Article

Turcanu, M.V., Stewart, F.R., Cox, B.F., Clutton, R.E., Mulvana, H., Vllasaliu, D., Thanou, M., Näthke, I., Cochran, S. (2018) Ultrasound and Microbubbles Promote the Retention of Fluorescent Compounds in the Small Intestine.  2018 IEEE International Ultrasonics Symposium, IUS 2018. 2018 October, 8580036. IEEE Computer Society 2018 IEEE International Ultrasonics Symposium, IUS 2018, Kobe Japan 22/10/18. doi/10.1109/ULTSYM.2018.8580036  Read Article

Lawler, M., Alsina, D., Adams, R., Anderson, A., Brown, G., Fearnhead, N.S., Fenwick, S.W., Halloran, S.P., Hochhauser, D., Hull, M.A., Koelzer, V.H., McNair, A.G.K., Monahan, K.J., Näthke, I., Norton, C., Novelli, M., Steele, R., Thomas, A.L., Wilde, L., Wilson, R.H., and Tomlinson, I. (2018) Critical research gaps and recommendations to inform research prioritisation for more effective prevention and improved outcomes in colorectal cancer. Colorectal Cancer. 67(1):179-193.  doi/1136/gutjnl-2017-315333 PMCID 5754857 PMID 29233930  Read Article

Langlands, A.J., Carroll, T.D., Chen, Y., Näthke, I. (2018) Chir99021 and Valproic acid reduce the proliferative advantage of Apc mutant cells. Cell Death and Disease. 9:1-10.  doi/10.1038/s41419-017-0199-9 PMCID 5833359 PMID 29449562  Read Article

Carroll, T., Newton, I., Chen, Y., Blow, J., Näthke, I. (2018) Lgr5+ intestinal stem cells reside in an unlicensed G1 phase. Journal of Cell Biology. 217(5): 1667-1685.  doi/10.1083/jcb.201708023 PMCID 5940300 PMID 29599208  Read Article

Stewart, F., Verbeni, A., Qiu, Y., Cox, B., Vorstius, J., Newton, I., Huang, Z., Menciassi, A., Näthke, I., and Cochran, S.  (2018) A prototype theraputic capsule endoscope for ultrasound-mediated targeted drug delivery. Journal of Medical Robotics Research. 3(2). doi.org/10.1142/S2424905X18400019  Read Article

Stewart, R., Mulvana, H., Näthke, I., Cochran, S. (2018) Theranostics in the Gut, Thanou, M, editor. In Theranostics and Image Guided Drug Delivery. United Kingdom: Royal Society of Chemistry. pp. 182-210. (Drug Discovery; 63)  doi/10.1039/9781788010597-00182.  Read Article

Almet, A.A., Hughes, B.D., Landman, K.A., Näthke, I., and Osborn, J.M. (2018). A multicellular model of intestinal crypt buckling and fission. Bulletin of Mathematical Biology. 80(2): 335-359. doi/10.1007/s11538-017-0377-z PMID 29234982  Read Article

Zhang, L., Jablonski, A. M., Mojsilovic-Petrovic, J., Ding, H., Seeholzer, S.,Newton, I. P., Näthke, I., Neve, R., Zhai, J., Shang, Y., Zhang, M., Kalb, R. G. (2017) SAP97 Binding Partner CRIPT Promotes Dendrite Growth In Vitro and In Vivo.  eNeuro 27 November 2017, 4 (6) ENEURO.0175-17.2017 doi.org/10.1523/ENEURO.0175-17.2017 PMCID 5718245 PMID 29218323  Read Article

Cochran, S., Button, T. W., Cox, B. F., Cumming, D. R. S., Gourevich, D.,Lay, H. S., Mulvana, H., Näthke, I.S., Stewart, F. (2017) Nanotechnology in multimodal theranostic capsule endoscopy. 2017 IEEE 17th International Conference on Nanotechnology (IEEE-NANO) doi/10.1109/NANO.2017.8117439  Read Article

Bentivegna, V., Stewart, F., Cochran, S., Näthke, I (2017) Acoustic radiation pressure as a versatile tool for cell compression and mechanobiology studies. 2017 IEEE International Ultrasonics Symposium (IUS)  doi/10.1109/ULTSYM.2017.8092765  Read Article

Carroll, T. D., Langlands, A. J., Osborne, J. M., Newton, I. P., Appleton, P. L., Näthke, I. (2017) Interkinetic nuclear migration and basal tethering facilitates post-mitotic daughter separation in intestinal organoids. Journal of Cell Science 2017 130: 3862-3877. doi/10.1242/jcs.211656 PMCID 5702049 PMID 28982714  Read Article

Stewart, F., Liu, Y., Roncin, P., Newton, I. P., Huang, Z., Näthke, I.,Cochran, S.. (2017) A fully-automated insonation system for in vitro investigations of ultrasound-mediated targeted drug delivery.  2017 IEEE International Ultrasonics Symposium (IUS) doi/10.1109/ULTSYM.2017.8091959.  doi/10.1109/ULTSYM.2017.8091959  Read Article

Stewart, F., Newton, I. P., Cox, B. F., Huang, Z., Näthke, I., Cochran, S. (2017) Development of a therapeutic capsule endoscope for treatment in the gastrointestinal Tract: Bench testing to translational trial. 2017 IEEE International Ultrasonics Symposium (IUS) doi/10.1109/ULTSYM.2017.8092467  Read Article

Näthke, I (2017) Cancer Biology: APC Delivers Kiss of Death to Focal Adhesions. Volume 27, Issue 16, 21 August 2017, Pages R805-R807. doi/10.1016/j.cub.2017.07.028 PMID 28829967  Read Article

 Stewart, F. R., Qiu, Y., Lay, H. S., Newton, I. P., Cox, B. F., Al-Rawhani, M. A., Beeley, J., Liu, Y., Huang, Z., Cumming, D. R. S., Näthke, I., Cochran, S. (2017) Acoustic Sensing and Ultrasonic Drug Delivery in Multimodal Theranostic Capsule Endoscopy. doi.10.3390/s17071553 PMCID 5539857 PMID 28671642  Read Article

Cox, B.F., Stewart, F., Lay, H., Cummins, G., Newton, I.P., Desmulliez, M.P.Y., Steele, R.J.C., Näthke, I., and Cochran, S. (2017) Ultrasound capsule endoscopy: sounding out the future. Annals of translational medicine. 5, 201. doi/10.21037/atm.2017.04.21 PMCID 5438792 PMID 28567381  Read Article

 Lay, H. S., Cox, B. F., Sunoqrot, M., Démoré, C. E. M., Näthke, I., Gomez, T., Cochran, S. (2017) Microultrasound characterisation of ex vivo porcine tissue for ultrasound capsule endoscopy. IOP Conf. Series: Journal of Physics: Conf. Series 797 (2017) 012003 doi/10.1088/1742-6596/797/1/012003  Read Article

Stewart, F., Cox, B. F., Wang, G., Huang, Z., Newton, I. P., Nathke, I.S.,Thanou, M., Cochran, S. (2016) An in vitro sonication system for applications in ultrasound-mediated targeted drug delivery.  2016 IEEE International Ultrasonics Symposium (IUS) 18-21 Sept. 2016. IEEE Xplore: 03 November 2016. doi/10.1109/ULTSYM.2016.7728701  Read Article

Cox, B. F., Stewart, F., Huang, Z., Nathke, I.S., Cochran, S. (2016) Ultrasound facilitated marking of gastrointestinal tissue with fluorescent material.  2016 IEEE International Ultrasonics Symposium (IUS) doi/10.1109/ULTSYM.2016.7728782  Read Article

Fatehullah, A., Sharma, S., Newton, I.P., Langlands, A.J., Lay, H., Nelson, S.A., McMahon, R.K., McIlvenny, N., Appleton, P.L., Cochran, S., and Näthke, I.S. (2016).  Increased variability in Apc(Min)/+intestinal tissue can be measured with microultrasound. Scientific Reports. 6, 29570. doi/10.1038/srep29570 PMCID 4942766 PMID 27406832  Read Article

Langlands, A.J., Almet, A.A., Appleton, P.L., Newton, I.P., Osborne, J.M. and Näthke, I.S. (2016) Paneth cell-rich regions Separated by a cluster of Lgr5+ cells initiate crypt fission in the intestinal stem cell niche. PLoS Biology. 14, e1002491.  doi/10.1371/journal.pbio.1002491 PMCID 4922642 PMID 27348469  Read Article

Dunn, S.J., Osborne, J.M., Appleton, P.L., Näthke, I. (2016) Combined changes in Wnt signalling response and contact inhibition induce altered proliferation in radiation-treated intestinal crypts.  Molecular biology of the cell. 27, 1863-1874.  doi/10.1091/mbc.E15-12-0854 PMCID 4884076 PMID: 27053661  Read Article

Boccitto, M., Doshi, S., Newton, I.P., Näthke, I., Neve, R., Dong, F., Mao, Y., Zhai, J., Zhang, L., and Kalb, R. (2016) Opposing actions of the synapse-associated protein of 97-kDa molecular weight (SAP97) and Disrupted in Schizophrenia 1 (DISC1) on Wnt/beta-catenin signalling.  Neuroscience. 326, 22-30.  doi/10.1016/j.neuroscience.2016.03.048 PMCID 4853273 PMID 27026592  Read Article

Gupta, K. K., Alberico, E. O., Näthke, I.S., et al. (2014) Promoting microtubule assembly: A hypothesis for the functional significance of the +TIP network. Bioessays 36(9): 818-826. doi/10.1002/bies.201400029  PMID 24943963  Read Article

Trani, D., Nelson, S. A., Näthke, I.S., et al. (2014) High-energy particle-induced tumorigenesis throughout the gastrointestinal tract. Radiat Res 181(2): 162-171. doi/10.1667/RR13502.1  PMID 24512616  Read Article

Januschke, J., and Näthke, I. (2014) Stem cell decisions: a twist of fate or a niche market? Seminars in cell & developmental biology 34, 116-123.  doi/10.1016/j.semcdb.2014.02.014 PMCID 4169664 PMID 24613913  Read Article

Hinck, L., and Näthke, I. (2014) Changes in cell and tissue organization in cancer of the breast and colon.  Current opinion in cell biology 26, 87-95.  doi/10.1016/j.ceb.2013.11.003 PMCID 3927155 PMID 24529250  Read Article

Dunn, S. J., Näthke, I.S., et al. (2013) Computational models reveal a passive mechanism for cell migration in the crypt. PLoS One 8(11): e80516.  doi/10.1371/journal.pone.0080516 PMCID 3832622 PMID 24260407  Read Article

Fatehullah, A., Appleton, P. L., Näthke, I.S. (2013) Cell and tissue polarity in the intestinal tract during tumourigenesis: cells still know the right way up, but tissue organization is lost. Philos Trans R Soc Lond B Biol Sci 368(1629): 20130014.  doi/10.1098/rstb.2013.0014 PMCID 3785964 PMID 24062584  Read Article

Nelson, S., Näthke, I.S. (2013) Interactions and functions of the adenomatous polyposis coli (APC) protein at a glance. J Cell Sci. 126, 873-877 doi/10.1242/jcs.100479 PMID 23589686  Read Article

Davis, E.J., Lachaud, C., Appleton, P., MacCartney, T.J., Näthke, I. and Rouse, J. (2012) DVC1 (Clorf124) recruits the p97 protein segregase to sites o DNA damage.  Nature structural & molecular biology. 19, 1093-1100. doi/10.1038/nsmb.2394 PMID 23042607  Read Article

Dikovskaya, D., Khoudoli, G., Näthke, I.S., et al. (2012) The adenomatous polyposis coli protein contributes to normal compaction of mitotic chromatin. PLoS One 7(6): e38102.  doi/10.1371/journal.pone.0038102 PMCID 3374815 PMID 22719865  Read Article

Klotz, D. M., Nelson, S. A., Näthke, I.S., et al. (2012) The microtubule poison vinorelbine kills cells independently of mitotic arrest and targets cells lacking the APC tumour suppressor more effectively. J Cell Sci 125(Pt 4): 887-895.  doi/10.1242/jcs.091843 PMCID 3311929 PMID 22399804  Read Article

Nelson, S. A., Li, Z., Näthke, I.S., et al. (2012) Tumorigenic fragments of APC cause dominant defects in directional cell migration in multiple model systems. Dis Model Mech 5(6): 940-947.  doi/10.1242/dmm.008607 PMCID 3484875 PMID 22563063  Read Article

Marshall, T.W., Lloyd, I.E., Delanande, J.M., Näthke, I.S., Rosenblatt, J. (2011) The tumor suppressor adenomatous polyposis coli controls the direction in which a cell extrudes from an epithelium.  Mol Biol Cell. 2011 Nov;22(21):3962-70. doi/10.1091/mbc.E11-05-0469 PMCID 3204059 PMID 21900494  Read Article

Näthke, I.S and Rocha, S. (2011) Antagonistic crosstalk between  APC and HIF-1α.  Cell Cycle. 10, 1545-1547. doi/10.4161/cc.10.10.15638 PMCID 3127156 PMID 21502812  Read Article

Buchert, M., Athineos, D., Abud, H. E., Burke, Z. D., Faux, M. C., Samuel, M. S., Jarnicki, A. G., Winbanks, C. E., Newton, I. P., Meniel, V. S., Suzuki, H., Stacker, S. A., Näthke, I.S., Tosh, D., Huelsken, J., Clarke, A. R., Heath, J. K., Sansom, O. J., Ernst, M. (2010) Genetic dissection of differential signaling threshold requirements for the Wnt/beta-catenin pathway in vivo. PLoS Genetics, 6, 1. e1000816. doi/10.1371/journal.pgen.1000816 PMCID 2800045 PMID 20084116  Read Article

Dikovskaya, D., Li, Z., Näthke, I.S., et al. (2010) Microtubule assembly by the Apc protein is regulated by importin-beta--RanGTP. J Cell Sci 123(Pt 5): 736-746. doi/10.1242/jcs.060806  PMID 20144988  Read Article

Jones, S. E. M., Joice, P., Cochrane, L., Thoresen, I., Quyn, A., Näthke, I (2010) Is familial adenomatous polyposis associated with sensorineural hearing loss? International Journal of Audiology. Volume 49, 2010 - Issue 10, 762-764. doi.org/10.3109/14992027.2010.491098 PMID 20874049  Read Article

Näthke, I (2010) The immortal DNA strand - difficult to digest? Response.  doi.org/10.1016/j.stem.2010.03.012  Read Article

Newton, I. P., Kenneth, N. S., Näthke, I.S., et al. (2010) Adenomatous polyposis coli and hypoxia-inducible factor-1{alpha} have an antagonistic connection. Mol Biol Cell 21(21): 3630-3638.  doi/10.1091/mbc.E10-04-0312 PMCID 2965681 PMID 20844082  Read Article

Quyn, A. J., Appleton, P. L., Näthke, I.S., et al. (2010) Spindle orientation bias in gut epithelial stem cell compartments is lost in precancerous tissue. Cell Stem Cell 6(2): 175-181.  doi/10.1016/j.stem.2009.12.007 PMID: 20144789  Read Article

Radulescu, S., Ridgway, R. A., Appleton, P., Kroboth, K., Patel, S.,Woodgett, J., Taylor, S., Näthke, I.S., Sansom, O. J (2010) Defining the role of APC in the mitotic spindle checkpoint in vivo: APC-deficient cells are resistant to Taxol. Oncogene volume29, pages6418–6427. doi/10.1038/onc.2010.373 PMCID 3016607 PMID 20729907  Read Article

Sedwick, C., Näthke, I. (2010) Inke Näthke: The ABCs of APC.  J Cell Biol. 2010 May 31;189(5):774-5. doi/10.1083/jcb.1895pi PMCID 2878947 PMID 20513763  Read Article

Appleton, PL, Quyn, AJ, Swift, S & Näthke, I (2009) Preparation of wholemount mouse intestine for high-resolution three-dimensional imaging using two-photon microscopy.  Journal of Microscopy, vol. 234, no. 2, pp. 196-204. doi/10.1111/j.1365-2818.2009.03163.x PMID 19397748  Read Article

Quyn, A, Steele, RJ, Carey, FA, Appleton, PL & Näthke, I. (2009) A Role for the APC Protein in Intestinal Crypt Fission Examined By Multi-Photon Microscopy. Gastroenterology, vol. 136, no. S5, pp. A454-A454.  doi.org/10.1111/j.1365-2818.2009.03163.x  Read Article

Quyn, A, Steele, RJ, Carey, FA, Appleton, PL & Näthke, I. (2009) A Role for the Adenomatous Polposis Coli Protein in Mitotic Spindle Alignment in Gut Epithelium.  Gastroenterology, vol. 136, no. S5, pp. A758-A758.

Li, Z, Kroboth, K, Newton, IP & Näthke, I.S. (2008) Novel self-association of the APC molecule affects APC clusters and cell migration.  Journal of Cell Science, vol. 121, no. 11, pp. 1916-1925.  doi.org/10.1242/jcs.029470 PMID 18477604  Read Article

McCartney, BM & Näthke, I.S (2008) Cell regulation by the Apc protein: Apc as master regulator of epithelia' Current Opinion in Cell Biology, vol. 20, no. 2, pp. 186-193.  doi.org/10.1016/j.ceb.2008.02.001 PMID 18359618  Read Article

Quyn, AJ, Steele, RJC, Carey, FA & Näthke, I.S (2008) Prognostic and therapeutic implications of APC mutations in colorectal cancer' Surgeon: Journal of the Royal Colleges of Surgeons of Edinburgh and Ireland, vol. 6, no. 6, pp. 350-356. PMID 19110823  Read Article