Meet Dr. Roger Moorehead
Keywords: Breast cancer, gene expression, lung cancer, mechanisms of tumour initiation and progression, microRNAs, RNA sequencing, signal transduction pathways, transgenic mouse models, tumorigenesis, xenograft mouse models
- Professor – Department of Biomedical Sciences, University of Guelph, Ontario Veterinary College
Seeking Partnerships in the Areas of:
Soy supplementation for preventing breast cancer; Technologies to increase microRNA expression in vivo; IGF1R targeting agents; AKT1 targeting agents
Education and Employment Background:
- PhD – Medical Sciences (McMaster University, Hamilton, Ontario, Canada)
- BSc – Medical Sciences (McMaster University, Hamilton, Ontario, Canada)
Research Themes & Interests:
Dr Moorehead’s research focuses on understanding the mechanisms behind the initiation and progression of breast and lung cancer. Using transgenic and knockout mice along with human and murine tumor cell lines the Moorehead lab is identifying genes and non-coding RNAs that regulate cell proliferation, apoptosis and migration. This research will improve our understanding of why tumors develop and spread throughout the body and may provide new therapeutic strategies for preventing or treating breast and lung cancer.
Some of the major research themes are listed below.
- The insulin-like growth factor family in breast cancer: The Moorehead lab created the first inducible transgenic mouse model of IGF1R overexpression in mammary epithelial cells. IGF1R overexpression induced mammary tumour development in 100% of the mice and metastatic tumours in ~30% of the mice. We have used this model to understand mammary tumor initiation, progression, metastasis and epithelial to mesenchymal transition (EMT). We have also used this model to demonstrate that IGF1R overexpression induces mammary tumors with characteristics of human basal-like and claudin-low breast cancer.
- The insulin-like growth factor family in lung cancer: The Moorehead lab created the first inducible transgenic mouse model to overexpress IGF1R in type II alveolar cells and Clara cells of the lung. Overexpression of IGF1R induced lung tumor development in 100% of the mice. Using this model and human lung cancer cell lines, it was shown that the downstream signaling molecule AKT1 promoted lung tumour development while the family member, AKT2 inhibited lung tumour development.
- The role of miR-200s in mammary tumor initiation and progression. Research in the Moorehead lab has found that a family of microRNAs known as the miR-200 family influences mammary tumour progression and metastasis. Re-expression of miR-200 family members in mouse and human triple negative mammary tumors restored some epithelial characteristics, delay mammary tumor development and inhibited metastasis.
- The impact of dietary soy on mammary tumorigenesis. Using the IGF1R transgenic mouse model described above, the Moorehead lab has found that diets containing a highly refined form of soy, known as isolated soy protein, promotes mammary tumor development. However, diets containing a less refined form of dietary soy, known as soybean meal, completely protected the mice from mammary tumor development. The isolated soy protein diet also differed in the type of carbohydrate and the levels of several vitamins, so Moorehead lab is currently investigating the complex interaction of soy with other dietary components to modulate breast cancer risk.
Recent Research Focuses & Partnerships:
- How signaling via tyrosine kinase receptors mediates tumor development.
- The impact of microRNAs on tumor growth and metastasis.
- Whether dietary soy can protect against mammary tumor development.
- Moorehead RA. Rodent models assessing mammary tumor prevention by soy or soy isoflavones. Genes (Basel) 2019 Jul 26;10(8):566. doi: 10.3390/genes10080566.
- Jones RA, Moorehead RA. Integrative analysis of copy number and gene expression data identifies potential oncogenic drivers that promote mammary tumor recurrence. Genes Chromosomes Cancer. 2019 Jun;58(6):381-391. doi: 10.1002/gcc.22729. Epub 2019 Jan 30. PMID:30597648
- Jones RA, Franks SE, Moorehead RA. Comparative mRNA and miRNA transcriptome analysis of a mouse model of IGFIR-driven lung cancer. PLoS One. 2018 Nov 9;13(11):e0206948. doi: 10.1371/journal.pone.0206948. eCollection 2018. PMID:30412601
- Watson, KL, Jones RA, Bruce A and Moorehead RA. The miR-200b/200a/429 cluster prevents metastasis and induces dormancy in a murine claudin-low mammary tumor cell line. Experimental Cell Research (in press).
- Chorner PM, Moorehead RA. A-674563, a putative AKT1 inhibitor that also suppresses CDK2 activity, inhibits human NSCLC cell growth more effectively than the pan-AKT inhibitor, MK-2206. PLoS One. 2018 Feb 22;13(2):e0193344.
- Jones R, Watson K, Bruce A, Nersesian S, Kitz J, Moorehead R. Re-expression of miR-200c suppresses proliferation, colony formation and in vivo tumor growth of murine claudin-low mammary tumor cells. Oncotarget. 2017 Apr 4;8(14):23727-23749.
- Linnerth-Petrik NM, Santry LA, Moorehead R, Jücker M, Wootton SK, Petrik J. Akt isoform specific effects in ovarian cancer progression. Oncotarget. 2016 Nov 15;7(46):74820-74833
- Saleh S, Thompson DE, McConkey J, Murray P, Moorehead RA. Osteopontin regulates proliferation, apoptosis, and migration of murine claudin-low mammary tumor cells. BMC Cancer. 2016 Jun 10;16:359.
- Franks SE, Jones RA, Briah R, Murray P, Moorehead RA. BMS-754807 is cytotoxic to non-small cell lung cancer cells and enhances the effects of platinum chemotherapeutics in the human lung cancer cell line A549. BMC Res Notes. 2016 Mar 1;9:134.
- Franks, SE, Briah, R, Jones, RA and Moorehead, RA. Unique roles of Akt1 and Akt2 in IGF-IR mediated lung tumorigenesis. Oncotarget. 2016 Jan 19;7(3):3297-316.
- Watson, KL, Stalker, L, Jones, RA and Moorehead, RA. High levels of dietary soy decrease mammary tumor latency and increase incidence in MTB-IGFIR transgenic mice. BMC Cancer 2015 Feb 6;15:37
- Jones, RA, Watson, KL, Campbell, CI and Moorehead, RA. IGF-IR mediated mammary tumorigenesis is enhanced during pubertal development. PLoS One 2014 Sep 26;9(9): e108781
- Stalker, L, Pemberton, J andMoorehead, RA. Inhibition of proliferation and migration of luminal and claudin-low breast cancer cells by PDGFR inhibitors. Cancer Cell Int 2014 Sep 5;14(1):89.
- Watson, KL and Moorehead RA. Loss of Akt1 or Akt2 delays mammary tumor onset and suppresses tumor growth rate in MTB-IGFIR transgenic mice. BMC Cancer 2013 13:375
- Thompson, D.E., Siwicky, M.D., and Moorehead, R.A. Caveolin-1 expression is elevated in claudin-low mammary tumor cells. Cancer Cell Int 2012 12:6Campbell, C.I. and Moorehead, R.A. Mammary tumors that become independent of the type I insulin-like growth factor receptor express elevated levels of platelet-derived growth factor receptors. BMC Cancer 2011 11:480
- Franks, S.E., Campbell, C.I., Barnett, E.F., Siwicky, M.D., Livingstone, J., Cory, S. and Moorehead, R.A.Transgenic IGF-IR overexpression induces mammary tumors with basal-like characteristics, whereas IGF-IR-independent mammary tumors express a claudin-low gene signature. Oncogene 2011 (epub ahead of print)
- Campbell, C.I., Thompson, D.E., Siwicky, M.D. and Moorehead, R.A. Murine mammary tumor cells with a cluadin-low genotype. Cancer Cell Int 2011 11;28
- Campbell, C.I., Petrik, J.J. and Moorehead, R.A. ErbB2 enhances mammary tumorigenesis, oncogene-independent recurrence and metastasis in a model of IGF-IR-mediated mammary tumorigenesis. Mol Cancer 2010 9:235
- Siwicky, M.D., Petrik, J.J., and Moorehead, R.A. The function of IGF-IR in NNK-mediated lung tumorigenesis. Lung Cancer 2011 71:11-18
- Jones, R.A., Petrik, J.J. and Moorehead, R.A. Preneoplastic changes persist after IGF-IR downregulation and tumor regression. Oncogne 2010 29:4779-4786
- Linnerth, N.M., Siwicky, M.D., Campbell, C.I., Watson, K.L.M., Petrik, J.J., Whitsett, J.A., and Moorehead, R.A. Type I insulin-like growth factor receptor induces pulmonary tumorigenesis. Neoplasia. 2009 11:672-682
- Jones, R.A., Campbell, C.I., Wood, G.A., Petrik, J.J., and Moorehead, R.A., Reversibility and recurrence of IGF-IR-induced mammary tumors. Oncogene. 2009 Apr 20. [Epub ahead of print]
- Greenaway, J., Henkin, J., Lawler, J., Moorehead, R., and Petrik, J. ABT-510 induces tumor cell apoptosis and inhibits ovarian tumor growth in an orthotopic, syngeneic model of epithelial ovarian cancer. Mol Cancer Ther. 2009 Jan;8(1):64-74.
- Jones, R.A., and Moorehead, R.A. The impact of transgenic IGF-IR overexpression on mammary development and tumorigenesis. J Mammary Gland Biol Neoplasia. 2008 Dec;13(4):407-13. Epub 2008 Nov 11. Review.
- Linnerth, N.M., Greenaway, J.B., Petrik, J.J., and Moorehead, R.A. cAMP response element-binding protein is expressed at high levels in human ovarian adenocarcinoma and regulates ovarian tumor cell proliferation. Int J Gynecol Cancer. 2008 Jun 11.
- Jones, R.A., Campbell, C.I., Petrik, J.J., and Moorehead, R.A. Characterization of a novel primary mammary tumor cell line reveals that cyclin D1 is regulated by the type I insulin-like growth factor receptor. Mol Cancer Res. 2008 May;6(5):819-28.
- Jones, R.A., Campbell, C.I., Gunther, E.J., Chodosh, L.A., Petrik, J.J., Khokha, R., and Moorehead, R.A. Transgenic overexpression of IGF-IR disrupts mammary ductal morphogenesis and induces tumor formation. Oncogene. 2007 Mar 8;26(11):1636-44. Epub 2006 Sep 4.
- Linnerth, N.L., Baldwin, M., Campbell, C., Brown, M., McGowan, H., and Moorehead, R.A. IGF-II induces CREB phosphorylation and cell survival in human lung cancer cells. Oncogene 2005 Nov; 10:24(49); 7310-9.
- Linnerth, N.L., Sirbovan, K., and Moorehead, R.A. Use of a Transgenic Mouse Model to Identify Markers of Human Lung Tumors. International Journal of Cancer 114:977-982, 2005.
- miR-200 research project has been funded by two Canadian Institutes of Health Research (CIHR) operating grants (2014-2019 and 2019-2024)
- dietary soy research funded by CIHR and the Canadian Cancer Society (CCS)
- lung cancer research funded by CCS
- CIHR New Investigator Salary Award 2005-2010
- U of G probing the value of consuming soy in preventing breast cancer (Guelph Mercury, 2010).
- The Connection between diet and breast cancer (Guelph Research Magazine, 2011; p.29).
- Innovative look at old molecule could lead to better outcomes for a hard-to-treat cancer. (Feb 24, 2015).
- Breast Cancer: Moving towards a cure (Guelph Research Magazine March, 2015; p.43)
Phone: (519) 824-4120 ext. 54950
Office: Biomed 3626
Ontario Veterinary College
University of Guelph
50 Stone Road E.,
Guelph, ON, Canada, N1G 2W1