Profile

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:

Cancer treatment tailor-made for your tumour (Newsroom)
Funding for research into tailor-made tumour treatment (RNZ)
Cancer research boosted by awards (Otago Daily Times)
Can old drugs put a leash on wandering cancer cells (stuff.co.nz)
Otago study takes closer look at DNA for clues on improving bowel cancer therapy (Pharmacy Today; requires login)
Southland Medical Foundation supports bowel cancer research project (stuff.co.nz)

Publications

Milne, T., Anwar, M., Burga, L., Harcombe, H., Garelja, M., Middleton, A., Ribeiro, D. C., Fleming, N., Ogbuehi, K., & Bahn, A. (Eds.). (2023). Proceedings of the 268th Otago Medical School Research Society (OMSRS) Meeting: Masters/Honours/Postgraduate Diploma Student Speaker Awards. Dunedin, New Zealand: OMSRS. Retrieved from https://ourarchive.otago.ac.nz/handle/10523/12839 Conference Contribution - Edited volume of conference proceedings

van der Werf, J., Chin, C. V., Dunbier, A., & Fleming, N. (2023). Influence of SNP rs1800795 on macrophage polarisation, colitis, and response to emerging therapies. Proceedings of the Genetics Otago (GO) Annual Symposium & Workshops. Retrieved from https://blogs.otago.ac.nz/go Conference Contribution - Published proceedings: Abstract

Milne, T., Anwar, M., Burga, L., Harcombe, H., Garelja, M., Middleton, A., Ribeiro, D. C., Fleming, N., Ogbuehi, K., & Bahn, A. (Eds.). (2023). Proceedings of the 267th Otago Medical School Research Society (OMSRS) Meeting: PhD Student Speaker Speaker Awards. Dunedin, New Zealand: OMSRS. Retrieved from https://ourarchive.otago.ac.nz/handle/10523/12839 Conference Contribution - Edited volume of conference proceedings

Milne, T., Anwar, M., Burga, L., Harcombe, H., Garelja, M., Middleton, A., Ribeiro, D. C., Fleming, N., Ogbuehi, K., & Bahn, A. (Eds.). (2023). Proceedings of the 266th Otago Medical School Research Society (OMSRS) Meeting: Research Staff Speaker Awards. Dunedin, New Zealand: OMSRS. Retrieved from https://ourarchive.otago.ac.nz/handle/10523/12839 Conference Contribution - Edited volume of conference proceedings

Milne, T., Anwar, M., Burga, L., Harcombe, H., Garelja, M., Middleton, A., Ribeiro, D. C., Fleming, N., Ogbuehi, K., & Bahn, A. (Eds.). (2023). Proceedings of the 265th Otago Medical School Research Society (OMSRS) Meeting: Summer Student Speaker Awards. Dunedin, New Zealand: OMSRS. Retrieved from https://ourarchive.otago.ac.nz/handle/10523/12839 Conference Contribution - Edited volume of conference proceedings

2023

Conference Contribution - Published proceedings: Abstract

Conference Contribution - Edited volume of conference proceedings

2022

Conference Contribution - Published proceedings: Abstract

Chin, A. C. V., van der Werf, J., Kallingappa, P., Brink, R., Merry, T. L., & Fleming, N. I. (2022). Successful modelling of a single nucleotide polymorphism in cells and mice using CRISPR-Cas9 and CRISPR-Cas12 methodologies. Proceedings of the Genetics Otago (GO) Annual Symposium. Retrieved from https://blogs.otago.ac.nz/go

Conference Contribution - Verbal presentation and other Conference outputs

Chin, A. C. V., van der Werf, J., Merry, T. L., & Fleming, N. I. (2022, August). Altered control of interleukin-6 during macrophage polarisation may contribute to colorectal cancer progression. Verbal presentation at the Cancer Satellite Meeting: Queenstown Research Week, Queenstown, New Zealand.

Watson, L., MacRae, C., Kallingappa, P., Fleming, N. I., & Merry, T. L. (2022, August). The paradoxical role of IL-6 in cardiometabolic health. Verbal presentation at the Metabolic & Cardiovascular Disease Satellite Meeting: Queenstown Research Week, Queenstown, New Zealand.

Chin, A. C. V., van der Werf, J., Kallingappa, P., Brink, R., Merry, T. L., & Fleming, N. I. (2022, August). Successful modelling of a single nucleotide polymorphism in cells and mice using CRISPR-Cas9 and CRISPR-Cas12 methodologies. Verbal presentation at the CRISPR Technologies Satellite Meeting: Queenstown Research Week, Queenstown, New Zealand.

Watson, L. E., MacRae, C., Fleming, N., D'Souza, R. F., & Merry, T. L. (2022, August-September). Understanding the role of the IL-6 -174 G/C (rs1800795) promoter variant in metabolic responses to exercise. Verbal presentation at the 16th New Zealand Medical Sciences Congress (MedSci), Queenstown, New Zealand.

2021

Journal - Research Other

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

2020

Journal - Research Article

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

2018

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

Conference Contribution - Published proceedings: Abstract

Munro, F., Gimenez, G., Shepherd, P., Braithwaite, A., McCall, J., & Fleming, N. (2018). A common variation in the IL6 promoter predicts time to metastasis for colorectal cancer and may indicate the mechanisms involved. Proceedings of the New Zealand Society for Oncology (NZSO) Conference. Retrieved from http://www.nzsoncology.org.nz/

Conference Contribution - Poster Presentation (not in published proceedings)

Henderson, L., Mehta, S., Fleming, N., Eccles, M., Chatterjee, A., Print, C., … Braithwaite, A. (2018, August). p63 promotes proliferation in melanoma cell lines via regulation of AQP3. Poster session presented at the Queenstown Molecular Biology (QMB) Meetings, Queenstown, New Zealand.

Conference Contribution - Verbal presentation and other Conference outputs

Munro, F. M., Gimenez, G., Shepherd, P. R., Braithwaite, A. W., McCall, J. L., & Fleming, N. I. (2018, August). Regulation of IL-6 is pivotal to outcome in colorectal cancer. Verbal presentation at the Queenstown Molecular Biology (QMB) Meetings, Queenstown, New Zealand.

2016

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

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

Conference Contribution - Verbal presentation and other Conference outputs

Fleming, N. (2016, March). Control of the IL6 by the p53 protein family. Verbal presentation at the Genetics Otago Symposium, Dunedin, New Zealand.

Fleming, N. I., Henderson, L. E., Campbell, H. G., Antony, J., Print, C. G., Baird, M., & Braithwaite, A. W. (2016, August-September). A common variation within the IL6 promoter may alter its control by the p53 protein family and influence cancer progression. Verbal presentation at the Queenstown Molecular Biology (QMB) Meetings, Nelson, New Zealand.

Mehta, S., Lasham, A., Woolley, A., Algie, M., Al Jabry, T., Ma, W., Fleming, N., Young, K., Parker, K., … Braithwaite, A. (2016, August-September). Role of YB-1 in cell cycle. Verbal presentation at the Queenstown Molecular Biology (QMB) Meetings, Nelson, New Zealand.

Campbell, H., Fleming, N., Roth, I., Vennin, C., McCall, J., Mehta, S., Wiles, A., Williams, G., … Baird, M., & Braithwaite, A. W. (2016, August-September). IL-6 signalling mediates tumorigenesis, invasion and metastasis driven by the Δ133p53 isoform. Verbal presentation at the Queenstown Molecular Biology (QMB) Meetings, Nelson, New Zealand.

2015

Conference Contribution - Poster Presentation (not in published proceedings)

Roth, I., Campbell, H., Rubio, C., Vennin, C., Wilson, M., Wiles, A., Williams, G., … Fleming, N., Baird, M., & Braithwaite, A. (2015, October). Does a variant of the tumour suppressor P53 play a role in tumour metastasis? Poster session presented at the Otago Spotlight Series: Cancer Research, Wellington, New Zealand.

Conference Contribution - Verbal presentation and other Conference outputs

Fleming, N., Henderson, L. E., Print, C. G., Baird, M. A., & Braithwaite, A. W. (2015, August). Tumour suppression mechanisms and pro-migratory signals. Verbal presentation at the Queenstown Molecular Biology (QMB) Meetings, Queenstown, New Zealand.

2014

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

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

Conference Contribution - Poster Presentation (not in published proceedings)

Roth, I., Rubio, C., Campbell, H., Fleming, N., Baird, M., & Braithwaite, A. (2014, September). The Δ133p53 isoform promotes secreted cytokine-dependent cell migration. Poster session presented at the Division of Health Sciences Research Forum: Learning Different Research Languages, Dunedin, New Zealand.

2013

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

2011

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

2010

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

2009

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

2004

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

2003

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

2002

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.

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

2001

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.

2000

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.