University of Dundee

Professor Inke Nathke

From molecules to tissue architecture
Position: 
Professor of Epithelial Biology and Cancer, Associate Dean 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

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. 
doi/10.1109/ULTSYM.2018.8580036
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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