Robert T. Cormier, PhD
Associate Professor, Medical School, Duluth Campus
Associate Professor, Medical School, Duluth Campus
Integrated Biosciences Graduate Program, PhD Program in Biochemistry, Molecular Biology and Biophysics
PhD, Oncology, University of Wisconsin-Madison
BS, University of Wisconsin-Madison
For more than two decades the focus of our research group has been the genetics of colorectal cancer. Four ongoing projects are characteristic of our work.
1. PLA2G2A gene and colorectal cancer. At the University of Wisconsin-Madison, work conducted in the laboratory Dr. William Dove identified the Pla2g2a gene as a component of the Mom1 locus (Cormier et al., Nature Genetics 1997; Oncogene, 2000), the first modifier gene of cancer identified in mammals following its positional cloning. Since moving to the University of Minnesota Medical School we have continued to work on understanding the mechanisms underlying Pla2g2a’srole in CRC. In a collaboration with researchers in the Netherlands we have shown that Pla2g2a confers resistance to tumorigenesis in the Muc2 knockout mouse model of inflammatory intestinal cancer and in AOM treated mice, in addition to its tumor resistance in ApcMin mice. Gene expression analysis has identified a large number of Pla2g2a target genes including Runx1. Using Runx1 conditional knockout mice we have shown that Runx1 is a novel tumor suppressor gene in the mouse GI tract. Most recently, in a collaboration with investigators in Rotterdam, mechanisms underlying Pla2g2a’s tumor resistance in the intestinal stem cell compartment were described (Schewe et al., Cell Stem Cell, July, 2016).
2. Sleeping Beauty Transposon Mutagenesis screens in mice. In a collaboration with Dr. David Largaespada and co-workers at the University of Minnesota-Twin Cities that spans more than a dozen years, we have conducted forward genetic screens in the GI tract of mice using the Sleeping Beauty transposon system. This work has led to the identification of more than a hundred candidate driver genes for colorectal cancer, described in publications in leading journals such as Science, Nature and PNAS.
3. Role of the ion channel genes KCNQ1 and CFTR in colorectal cancer. Two ion channel genes that were initially identified as candidate cancer driver genes in Sleeping Beauty mutagenesis, KCNQ1 (Than et al.,Oncogene 2014; den Uil, British Journal of Cancer, 2016) and CFTR (Than et al., Oncogene, 2016), have been confirmed by our group as novel tumor suppressor genes in both mouse models and in human colorectal cancer. We have found that expression of both KCNQ1 and CFTR is associated with disease-free survival in early stage CRC and with a significant 23-month survival advantage in CRC patients with liver metastasis (KCNQ1). Our findings for CFTR are consistent with the high susceptibility for colorectal tumor development in cystic fibrosis patients who are CFTR homozygous mutants. Preliminary work indicates that both KCNQ1 and CFTR may influence the intestinal stem cell compartment. To further investigate this question we have created 3D organoids from the small and large intestine of mice and humans. Our results indicate that organoids deficient for either KCNQ1 or CFTR demonstrate abnormal growth phenotypes, including organoid number, growth and differentiation.
4. Disease modeling in transgenic golden Syrian hamsters. In collaboration with Dr. Zhongde Wang at Utah State University we are testing the first genetically engineered golden Syrian hamster models of human disease. Hamster knockouts and knockins were created using CRISPR/Cas9-mediated gene targeting, piggyBac-mediated transgenesis and pronuclear injection. We are currently studying mechanisms underlying a novel cancer syndrome in KCNQ1 KO hamsters (Li et al., 2018), as well as widespread cancer development in TP53 KO hamsters. We are also interested in the role of cholesteryl ester transfer protein (CETP) mutant hamsters in disorders of the GI tract.
See full list of publications at: PubMed
Patricia M Scott, Kyle J Anderson, Mekhla Singhania, and Robert Cormier. Cystic Fibrosis, CFTR and Colorectal Cancer. International Journal of Molecular Sciences. 2020, 21, 2891; doi:10.3390/ijms21082891.
Anderson, KJ, Cormier, RT, Scott, PM. The role of ion channel genes in gastrointestinal cancer. World Journal of Gastroenterology, 2019, Oct 14;25(38):5732-5772. doi: 10.3748/wjg.v25.i38.5732.
Rong Li, Jinxin Miao, M. Gerald O’Sullivan, Alexandre-Flaviu Tabaran, Kyle J. Anderson, Patricia M. Scott, Zhongde Wang, and Robert T. Cormier. A novel cancer syndrome caused by KCNQ1-deficiency in the golden Syrian hamster. J. Carcinogenesis, 2018, Oct 10;17:6. doi: 10.4103/jcar.JCar_5_18. eCollection 2018.PMID:30450013.
Den Uil, SH, Coupe, VMH, van den Broek, E, Goos, JACM, Delis-van Diemen PM, Belt, EJT, van Grieken, NCT, Scott, PM, Vermeulen, L, Medema, JP, Bril, H, Stockmann, HBAC, Cormier, RT, Meijer, GA, Fijneman, RJA. Loss of KCNQ1 expression in stage II and stage III colon cancer is a strong prognostic factor for disease recurrence. British Journal of Cancer, Nov 17, 2016 ePub before Print. Doi: 10.1038/BJC.2016.376. PMID: 27855440.
Matthias Schewe, Patrick F. Franken, Andrea Sacchetti, Rosalie Joosten, René Bottcher, Martin E. van Royen, Nancy R. Webb, Patricia M. Scott, Robert T. Cormier, Gerard Lambeau, and Riccardo Fodde. Secretory phospholipases are stem cell niche factors with distinct roles in intestinal homeostasis, inflammation and cancer. Cell Stem Cell, July 7, 2016. Published on line May 23, 2016. Http://dx.doi.org/10.1016/j.stem.2016.05.023.
Than, BLN, Linnekamp, JF, Starr, TK, Largaespada, DA, Rod, A, Zhang, Y, Bruner, V, Abrahante, J, Schumann, A, Luczak, T, Niemczyk, A, O’Sullivan, MG, Medema, JP, Fijneman, R, Meijer, G, Van den Broek, E, Hodges, C, Scott, PM, Vermeulen, L, and Cormier, RT. CFTR is a tumor suppressor gene in murine and human intestinal cancer. Oncogene, August 11, 2016. Advance online publication, 11 January 2016; doi:10.1038/onc.2015.483.
Than, BLN, Goos, JACM, Sarver, A L, O’Sullivan, MG, Rod, A, Starr, TK, Fijneman, RJA, Meijer, G, Zhang, Y, Zhao, L, Largaespada, DA, Scott, PM, and Cormier, RT The role of KCNQ1 in mouse and human gastrointestinal cancers. Oncogene. 2014 Jul 17;33(29):3861-8. doi: 10.1038/onc.2013.350. Epub 2013 Aug 26
Bagley, BN, Maklakova, V, Keane, T, Marshall, JG, Lester, RA, Cancel, MM, Bendzick, LE, Been, RA, Kogan, SC, Cormier, RT, Kendziorski, C, Adams, D and Collier, LS. A dominantly acting allele of murine Mcm4 causes chromosome instability and promotes leukemiogenesis. PLos Genet 2012;8(11):e1003034. doi: 10.1371/journal.pgen.1003034. Epub 2012 Nov 1.
Fijneman, RJA, Anderson, R, Richards, E, Liu, J, Tijssen, M, Meijer, GA, Rod, A, O’Sullivan, MG, Scott, PM, and Cormier, RT. (2012). Runx1 is a tumor suppressor gene in the mouse gastrointestinal tract. Cancer Science, 2012 Mar;103(3):593-9
Starr, TK, Scott, PM, Marsh, BM, Zhao, L., Than, BLN, M. O'Sullivan, MG, Sarver, AL, Dupuy, AJ, Largaespada, DA and Cormier, RT. (2011). A Sleeping Beauty transposon mediated screen identifies new murine susceptibility genes for Apc-dependent intestinal tumorigenesis. Proceedings National Academy Science USA, 108 (14)5765-5770
Fijneman, RJA, Bade, LK, Peham, JR, van de Wiel, MA, van Hinsbergh, VWM, Meijer, GA, O’Sullivan, MG, and Cormier, RT.(2009). Expression of Pla2g2a prevents tumorigenesis in azoxymethane-treated C57BL/6 mice; gene expression studies reveal Pla2g2a target genes in mouse colon. Cellular Oncology, 31 (5), 345-356.
Starr, TK, Allaei, R, Silverstein, KAT, Staggs, RA, Bergemann, T, O’Sullivan, MG, Matise, I., Dupuy, AJ, Collier, LS, Powers, S, Thibodeau, SN, Tessarollo, L, Copeland, NG, Jenkins, NA, Cormier, RT and Largaespada, DA. (2009). A Sleeping Beauty Transposon-based screen identifies genes altered in human colorectal cancer. Science, 323: 1747-1750.
Fijneman, RJA, Peham, JR, van de Wiel, MA, Meijer, GA, Matise, I, Velcich, A, and Cormier, RT. (2008). Expression of Pla2g2a prevents carcinogenesis in Muc2-deficient mice. Cancer Science, 99 (11): 2113-2119.
Bogan, C, Chen, J, O’Sullivan, MG and Cormier, RT. (2008). Loss of EphA2 receptor tyrosine kinase reduces ApcMin/+ tumorigenesis. International Journal of Cancer, 124 (6), 1366-1371.
Yang, K, Popova, NV, Yang, W, Lozonschi, I, Tadesse, S, Kent, S., Bancroft, L, Matise, I, Cormier, RT, Scherer, S, Edelmann, W, Lipkin, M., Augenlicht, L and Velcich, A. (2008). Interaction of Muc2 and Apc on Wnt signaling and in intestinal tumorigenesis: potential role of chronic inflammation. Cancer Research, 68 (18): 7313-7322.
Genetics: Molecular Genetics, Classical Genetics, Medical Genetics and Cancer Genetics; Gastrointestinal Cancer.
Mentoring & Advising: In the past fifteen years, our research group has advised more than 50 research trainees at the undergraduate, graduate (Ph.D., M.S.), post doctoral, and visiting scholar level. Our group currently includes six trainees.