Robert T. Cormier

Associate Professor

Essentia Health Chair in Cancer Biology

Links

Academic Health Center Graduate Programs
Integrated Biosciences Graduate Program


Research

Research in our laboratory is focused on the identification and characterization of susceptibility genes for colorectal cancer and involves analysis of both human cancer tissues and mouse models of colorectal cancer (CRC). In particular, studies employing forward and reverse genetics in mouse models are used to clone cancer susceptibility genes whose human homologues can be evaluated clinically. For example, the Apc^Min (Multiple Intestinal Neoplasia) mouse, which carries a dominant mutation in the Apc gene, has been shown to be a valuable model of human CRC. We are investigating genes in the Mom1 locus that confer resistance to Min-induced tumorigenesis. Mom1 is a complex of genes consisting of the secretory phospholipase Pla2g2a and one or more distal components. Several ongoing experiments seek to understand the genetic and biochemical basis for Pla2g2a’s tumor resistance, especially in the mouse colon. Additional mouse genetics studies in the lab include using targeted mutagenesis to study the role of potential genetic modifiers of Min such as Runx1, PPAR gamma, Muc2, EphA2, Parp1, Pax6, Kcnq1, Cftr and MCT1.

Another major project in our laboratory is a forward genetic screen in mice that utilizes Sleeping Beauty transposon-mediated mutagenesis to identify driver genes for gastrointestinal cancer. Screens performed in Apc wildtype and Apc^Min mice have identified more than 100 novel candidate cancer genes. Ongoing research involves the functional validation of these candidate cancer genes in human colon cancer cell culture, in genetically engineered mouse models and in human colorectal cancers.

Studies in human colorectal cancers involve whole genome, whole exome and whole transcriptome analyses using next generation sequencing to identify genes that function as drivers of colorectal cancer progression, genes that can be used as clinical prognostic predictors, and genes involved in resistance to therapy. A novel class of candidate driver mutations in human colorectal cancers of particular focus in our group are fusion oncogenes.

Students in our laboratory acquire training in various aspects of mouse cancer genetics including linkage-based gene mapping, targeted mutagenesis in embryonic stem cells, aspects of intestinal tumor biology, cancer cell biology, colon cancer stem cells, bioinformatics analysis of cancer genomes and transcriptomes and fundamentals of mouse husbandry

Publications

Publication listing on PubMed

Selected Papers:

Bruce N. Bagley, Vilena Maklakova, Thomas Keane, Jonathon G Marshall
Rachael A Lester, Michelle M Cancel, Laura E Bendzick , Raha A Been, Scott C. Kogan, Robert T Cormier, Christina Kendziorski, David Adams and Lara S. Collier. (2012). A dominantly acting allele of murine Mcm4 causes chromosome instability and promotes leukemiogenesis. (PLoS Genetics, in press)

Bergemann, T.L., Starr, T.K., Yu, H., Michael Steinbach, M., Chen, Y., Robert T. Cormier, R.T., Largaespada, D.A. and Kevin A.T. Silverstein, K.A.T. (2012). New methods for finding common insertion sites and co-occurring common insertion sites in transposon- and virus-based genetic screens. Nucleic Acids Research, 2012 May;40(9):3822-33.

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):593-92011.

Starr, T.K., Scott, P.M., Marsh, B.M., Zhao, L., Than, B.L.N., M. Gerard O'Sullivan, M.G., Sarver, A.L., Dupuy, A.J., David A. Largaespada, D.A. and Cormier, R.T. (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.

Cormier, R.T. PLA2G2A (Phospholipase A2, group IIA (Platelets, synovial fluid). Atlas Genet Cytogenet Oncol Haematol. March 2010.

Starr, T.K., Allaei, R., Silverstein, K.A.T., Staggs, R.A., Bergemann, T., O’Sullivan, M.G., Matise, I., Dupuy, A.J., Collier, L.S., Powers, S., Thibodeau, S.N., Tessarollo, L., Copeland, N.G., Jenkins, N.A., Cormier, R.T. and Largaespada, D.A. (2009). A Sleeping Beauty Transposon-based screen identifies genes altered in human colorectal cancer. Science, 323: 1747-1750.

Fijneman, R.J.A., Bade, L.K., Peham, J.R., van de Wiel, M.A., van Hinsbergh, V.W.M., Meijer, G.A., O’Sullivan, M.G., and Cormier, R.T. (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.

Fijneman, R. J. A. and Cormier, R.T. (2008). The putative roles of sPLA2-IIA (Pla2g2a) in cancer of the small and large intestine. Frontiers in Bioscience, 4144-4174, May, 2008.

Yang, K., Popova, N.V., Yang, W., Lozonschi, I., Tadesse, S., Kent, S., Bancroft, L., Matise, I., Cormier, R.T., Scherer, S., Edelmann, W., Lipkin, M., Leonard Augenlicht, A. and Anna 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.

Bogan, C., Chen, J., O’Sullivan, M.G. and Cormier, R.T. (2008). Loss of EphA2 receptor tyrosine kinase reduces Apc^Min/+ tumorigenesis. International Journal of Cancer, 124 (6), 1366-1371.

Fijneman, R.J.A., Peham, J.R., van de Wiel, M.A, Meijer, G.A, Matise, I., Velcich, A., and Cormier, R.T. (2008). Expression of Pla2g2a prevents carcinogenesis in Muc2-deficient mice. Cancer Science, 99 (11): 2113-2119.

McAlpine, C.A., Barak, Y., Matise, I., and R.T. Cormier (2006). Intestinal-specific PPARγ deficiency enhances tumorigenesis in Apc ^Min/+ mice. International Journal of Cancer 119, 2339-2346.