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Dr Nicholas Fleming

Contact Details

Phone
+64 3 479 7169
Email
nicholas.fleming@otago.ac.nz

University Links

Position
Sir Charles Hercus Health Research Fellow and Senior Research Fellow
Department
Department of Pathology (Dunedin)
Qualifications
PhD(Medicine)
Research summary
Mechanisms of cancer establishment and progression
Teaching

  • Research student supervision: 4 Summer Studentships, 2 Honours students, 2 PhD candidates
  • Lecturer for PATH 301 and PATH 302
  • Tutor for ELM2 ChemPath (3 topics)

Memberships

  • Member, MelNet 2017–present
  • Affiliate member, Maurice Wilkins Centre for Molecular Discovery (MWC) 2014–present
  • Member, New Zealand Society for Oncology (NZSO) 2012–present
  • Member, Otago Institute for the Arts and Sciences 2012–present
  • Member, Centre of Translational Cancer Research (CTCR) 2012–present
  • Member, Endocrine Society of Australia (ESA) 2008–2012
  • Associate Member, American Association for Cancer Research (AACR) 2005–present

Research

​​My research programme is currently focused on transcriptional and translational controls on gene and protein function relevant to cancer progression, and the crossover between the seemingly separate areas of energy metabolism, cancer associated inflammation, and metastasis. I have a special interest in colorectal cancer, but also cancers of the skin, breast, and ovaries.

My work loosely centres on the pivotal actions of the C/EBP family of transcription factors, and explores how these may switch from anti-cancer suppressors to metastasis-driving oncogenes. In this context, I am examining how existing drugs can be re-purposed for use in cancers, and also I am identifying factors and biomarkers that can predict response to immune checkpoint inhibitors. In addition, I am examining the contributions that non-coding RNAs make to these processes, and performing large scale genomic studies to identify genetic features that alter the way cancers progress in different people. My overall aim is to improve cancer prognostication and treatment strategies.​

More general:

  • Cancer genetics
  • Cancer genomics
  • Cancer cell biology
  • Cancer cell biochemistry
  • In vivo modelling
  • Molecular biology
  • Breast cancer
  • Colorectal cancer
  • Ovarian cancer
  • Melanoma
  • Tumour initiation
  • Tumour growth
  • Metastasis
  • C/EBP family function
  • p53 family function
  • TGF-β pathway function
  • mTOR pathway function
  • Role of proinflammatory signalling in cancer

Recently in the media:

Publications

van der Werf, J., Chin, C. V., & Fleming, N. I. (2021). SnoRNA in cancer progression, metastasis and immunotherapy response. Biology, 10, 809. doi: 10.3390/biology10080809

Eiholzer, R. A., Mehta, S., Kazantseva, M., Drummond, C. J., McKinney, C., Young, K., … Fleming, N., Morrin, H. R., Reader, K., Royds, J. A., Landmann, M., Petrich, S., … Taha, A., Hung, N. A., Slatter, T. L., & Braithwaite, A. W. (2020). Intronic TP53 polymorphisms are associated with increased Δ133TP53 transcript, immune infiltration and cancer risk. Cancers, 12(9), 2472. doi: 10.3390/cancers12092472

Campbell, H., Fleming, N., Roth, I., Mehta, S., Wiles, A., Williams, G., … Munro, F., McNoe, L., Black, M., McCall, J., Slatter, T. L., … Braithwaite, A. W. (2018). Δ133p53 isoform promotes tumour invasion and metastasis via interleukin-6 activation of JAK-STAT and RhoA-ROCK signalling. Nature Communications, 9(1), 254. doi: 10.1038/s41467-017-02408-0

Slatter, T. L., Wilson, M., Tang, C., Campbell, H. G., Ward, V. K., Young, V. L., … Fleming, N. I., Braithwaite, A. W., & Baird, M. A. (2016). Antitumor cytotoxicity induced by bone-marrow-derived antigen-presenting cells is facilitated by the tumor suppressor protein p53 via regulation of IL-12. OncoImmunology, 5(3), e1112941. doi: 10.1080/2162402X.2015.1112941

Roth, I., Campbell, H., Rubio, C., Vennin, C., Wilson, M., Wiles, A., Williams, G., Woolley, A., … Fleming, N., Baird, M., & Braithwaite, A. W. (2016). The Δ133p53 isoform and its mouse analogue Δ122p53 promote invasion and metastasis involving pro-inflammatory molecules interleukin-6 and CCL2. Oncogene, 35, 4981-4989. doi: 10.1038/onc.2016.45

Eiholzer, R. A., Mehta, S., Kazantseva, M., Drummond, C. J., McKinney, C., Young, K., … Fleming, N., Morrin, H. R., Reader, K., Royds, J. A., Landmann, M., Petrich, S., … Taha, A., Hung, N. A., Slatter, T. L., & Braithwaite, A. W. (2020). Intronic TP53 polymorphisms are associated with increased Δ133TP53 transcript, immune infiltration and cancer risk. Cancers, 12(9), 2472. doi: 10.3390/cancers12092472

Journal - Research Article

Campbell, H., Fleming, N., Roth, I., Mehta, S., Wiles, A., Williams, G., … Munro, F., McNoe, L., Black, M., McCall, J., Slatter, T. L., … Braithwaite, A. W. (2018). Δ133p53 isoform promotes tumour invasion and metastasis via interleukin-6 activation of JAK-STAT and RhoA-ROCK signalling. Nature Communications, 9(1), 254. doi: 10.1038/s41467-017-02408-0

Journal - Research Article

Roth, I., Campbell, H., Rubio, C., Vennin, C., Wilson, M., Wiles, A., Williams, G., Woolley, A., … Fleming, N., Baird, M., & Braithwaite, A. W. (2016). The Δ133p53 isoform and its mouse analogue Δ122p53 promote invasion and metastasis involving pro-inflammatory molecules interleukin-6 and CCL2. Oncogene, 35, 4981-4989. doi: 10.1038/onc.2016.45

Journal - Research Article

Slatter, T. L., Wilson, M., Tang, C., Campbell, H. G., Ward, V. K., Young, V. L., … Fleming, N. I., Braithwaite, A. W., & Baird, M. A. (2016). Antitumor cytotoxicity induced by bone-marrow-derived antigen-presenting cells is facilitated by the tumor suppressor protein p53 via regulation of IL-12. OncoImmunology, 5(3), e1112941. doi: 10.1080/2162402X.2015.1112941

Journal - Research Article

Diesch, J., Sanij, E., Gilan, O., Love, C., Tran, H., Fleming, N. I., … Dhillon, A. S. (2014). Widespread FRA1-dependent control of mesenchymal transdifferentiation programs in colorectal cancer cells. PLoS ONE, 9(3), e88950. doi: 10.1371/journal.pone.0088950

Journal - Research Article

Shalev, I., Moffitt, T. E., Braithwaite, A. W., Danese, A., Fleming, N. I., Goldman-Mellor, S., … Poulton, R., Robertson, S. P., … Caspi, A. (2014). Internalizing disorders and leukocyte telomere erosion: A prospective study of depression, generalized anxiety disorder and post-traumatic stress disorder. Molecular Psychiatry, 19, 1163-1170. doi: 10.1038/mp.2013.183

Journal - Research Article

Fleming, N. I., Jorissen, R. N., Mouradov, D., Christie, M., Sakthianandeswaren, A., Palmieri, M., … Sieber, O. M. (2013). SMAD2, SMAD3 and SMAD4 mutations in colorectal cancer. Cancer Research, 73(2), 725-735. doi: 10.1158/0008-5472.CAN-12-2706

Journal - Research Article

Sakthianandeswaren, A., Christie, M., D'Andreti, C., Tsui, C., Jorissen, R. N., Li, S., Fleming, N. I., … Sieber, O. M. (2011). PHLDA1 expression marks the putative epithelial stem cells and contributes to intestinal tumorigenesis. Cancer Research, 71(10), 3709-3719. doi: 10.1158/0008-5472.CAN-10-2342

Journal - Research Article

Fleming, N. I., Knower, K. C., Lazarus, K. A., Fuller, P. J., Simpson, E. R., & Clyne, C. D. (2010). Aromatase is a direct target of FOXL2: C134W in granulosa cell tumors via a single highly conserved binding site in the ovarian specific promoter. PLoS ONE, 5(12), e14389. doi: 10.1371/journal.pone.0014389

Journal - Research Article

Fleming, N. I., Trivett, M. K., George, J., Slavin, J. L., Murray, W. K., Moseley, J. M., … Thomas, D. M. (2009). Parathyroid hormone—related protein protects against mammary tumor emergence and is associated with monocyte infiltration in ductal carcinoma in situ. Cancer Research, 69(18), 7473-7479. doi: 10.1158/0008-5472.CAN-09-0194

Journal - Research Article

Thomas, D. M., Fleming, N. I., Holloway, A. J., & Bowtell, D. D. L. (2004). Molecular medicine: A clinician's primer on microarrays. Internal Medicine Journal, 34(9-10), 565-569. doi: 10.1111/j.1445-5994.2004.00680.x

Journal - Research Article

Gill, H., Cheadle, J. P., Maynard, J., Fleming, N., Whatley, S., Cranston, T., … Clarke, A. (2003). Mutation analysis in the MECP2 gene and genetic counselling for Rett syndrome. Journal of Medical Genetics, 40(5), 380-384. doi: 10.1136/jmg.40.5.380

Journal - Research Article

Al-Tassan, N., Chmiel, N. H., Maynard, J., Fleming, N., Livingston, A. L., Williams, G. T., … Cheadle, J. P. (2002). Inherited variants of MYH associated with somatic G:C→T:A mutations in colorectal tumors. Nature Genetics, 30(2), 227-232. doi: 10.1038/ng828

Journal - Research Article

Cheadle, J. P., Krawczak, M., Thomas, M. W., Hodges, A. K., Al-Tassan, N., Fleming, N., & Sampson, J. R. (2002). Different combinations of biallelic APC mutation confer different growth advantages in colorectal tumours. Cancer Research, 62(2), 363-366.

Journal - Research Article

Fleming, N., Maynard, J., Tzitzis, L., Sampson, J. R., & Cheadle, J. P. (2001). LD-PCR coupled to long-read direct sequencing: An approach for mutation detection in genes with compact genomic structures. Journal of Biochemical & Biophysical Methods, 47(1-2), 131-136.

Journal - Research Article

Cheadle, J. P., Gill, H., Fleming, N., Maynard, J., Kerr, A., Leonard, H., … Clarke, A. (2000). Long-read sequence analysis of the MECP2 gene in Rett syndrome patients: Correlation of disease severity with mutation type and location. Human Molecular Genetics, 9(7), 1119-1129.

Journal - Research Article

van der Werf, J., Chin, C. V., & Fleming, N. I. (2021). SnoRNA in cancer progression, metastasis and immunotherapy response. Biology, 10, 809. doi: 10.3390/biology10080809

Journal - Research Other

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