Robert Cormier

Contact Information Phone: 218-726-8625 Fax: Email: rcormier@d.umn.edu Address: 247 SMed 1035 University Dr. Duluth, MN 55812

Assistant Professor

Links

Academic Health Center Graduate Programs

Research

Research in our laboratory is focused on the mapping and functional characterization of genetic modifiers of colorectal cancer (CRC). While identifying these genes directly in humans is difficult, mouse models can be used to clone cancer susceptibility genes whose human homologues can be evaluated clinically. The 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. Studies are currently underway to identify the distal Mom1 gene.

Additional projects in the lab include: using targeted mutagenesis to study the role of potential genetic modifiers of Min such as PPAR gamma, MUC2, EphA2, and MCT1; understanding how altered DNA methylation affects Min tumorigenesis; and identification of genes critical for intestinal cancer metastasis using transposon mediated mutagenesis.

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 and fundamentals of mouse husbandry.

Laboratory Personnel

Christina Bogan, Junior Laboratory Technician

Publications

Publication listing on PubMed

Selected Papers

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. Expression of Pla2g2a prevents tumorigenesis in azoxymethane-treated C57BL/6 mice; gene expression studies reveal Pla2g2a target genes in mouse colon. Cellular Oncology 2008, submitted.

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. A Sleeping Beauty Transposon-based screen identifies genes altered in human colorectal cancer. Science, September, 2008; submitted.

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, in press.

Bogan, C., Chen, J., O’Sullivan, M.G. and Cormier, R.T. (2008). Loss of EphA2 receptor tyrosine kinase reduces Apc^Min/+ tumorigenesis. Int J Cancer, in press.

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 Res, 68 (18): 7313-7322.

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

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

Cormier, R.T. and W.F. Dove (2000).  Dnmt1 ^N/+ Reduces the Net Growth Rate and Multiplicity of Intestinal Adenomas in C57BL/6-Multiple Intestinal Neoplasia (Min)/+ Mice Independently of p53 but Demonstrates Strong Synergy with the Modifier of Min 1 ^AKR Resistance Allele.  Cancer Res 60: 3965-3970.

Cormier, R.T., Bilger, A., Lillich, A.J., Halberg, R.B., Hong, K.H., Gould, K.A., Borenstein, N., Lander, E.S., and W.F. Dove (2000).  The Mom1 ^AKR Intestinal Tumor Resistance Region Consists of Pla2g2a and a Locus Distal to D4Mit64.  Oncogene 19: 3182-3192.

Dove, W.F., Cormier, R.T., Gould, K.A., Halberg, R.B., Merritt, A.J., Newton, M.A., and A.R. Shoemaker (1998).  The Intestinal Epithelium and Its Neoplasms:  Genetic, Cellular, and Tissue Interactions.  Philosophical Transactions of the Royal Society of London: Biological Sciences.  May, 1998.

Cormier, R.T., Hong, K.H., Halberg, R.B., Hawkins, T.L., Richardson, P., Mulherkar, R., Dove, W.F., and E.S. Lander (1997).  Secretory Phospholipase Pla2g2a Confers Resistance to Intestinal Tumorigenesis.  Nature Genetics 17: 89-91.

Published Abstracts

Timothy K. Starr, Raha Allaei, Kevin A. T. Silverstein, Rodney A. Staggs, Tracy L. Bergemann, M. Gerard O’Sullivan, Ilze Matise, Adam J. Dupuy, Lara S. Collier, Scott Powers, Ann L. ObergStephen N. Thibodeau, Lino Tessarollo, Neal G. Copeland, Nancy A. Jenkins, David A. Largaespada andRobert T. Cormier . Intestinal cancer gene discovery using Sleeping Beauty-induced mutagenesis in Apc ^+/+ and Apc ^Min/+ mice. 22^nd  Annual International  Mouse Genome Conference, Prague, Czech Republic, November, 2008.

Wehmas, L.C. and Cormier, R.T. Estrogen Receptor Beta’s Role as a Tumor Suppressor in the Intestine of Apc ^Min/+ Mice. International Student Congress of the Biomedical Sciences, Groningen, Netherlands, June, 2008.

Fijneman, R.J.A., Bade, L.K., Peham, J.R., van de Wiel, M.A., van Hinsbergh, V.W.M., Meijer, G.A., and Cormier^, R.T. Expression profiling of mouse colon reveals Pla2g2a target genes. European Multidisciplinary Colorectal Cancer Congress 2008. Berlin, Germany, February, 2008.

Fijneman, R.J.A., Bade, L.K., Peham, J.R., van de Wiel, M.A., van Hinsbergh, V.W.M., Meijer, G.A., and Cormier^, R.T. Expression profiling of mouse colon reveals Pla2g2a target genes. International Society for Clinical Oncology 2008. Amsterdam, Netherlands March, 2008.

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. Expression of Pla2g2a prevents tumorigenesis in azoxymethane-treated C57BL/6 mice; gene expression studies reveal Pla2g2a target genes in mouse colon. 21^st Annual International  Mouse Genome Conference, Kyoto, Japan, October, 2007.

Starr, T.K., Allaei, R., Staggs, R.A., Silverstein, K.A., Dupuy, A.J., Jenkins, N.A., Copeland, N.C., Cormier, R.T. and Largaespada, D.A.. Identification of Driver Mutations in Gastrointestinal Tract Cancer. American Association for Cancer Research. Molecular Targets and Cancer Therapeutics, October 2007, San Francisco, CA.

Collier, L.S., Green, L.E., Hackett, C.S., Hodgson, J.G., Weiss, W.A., Cormier, R.T. and Largaespada, D.L. Treacherous transposition? 5th Annual International Conference on Transposition & Animal Biotechnology. 2007.

Cormier, R.T., Matise, I., and Velcich, A. Expression of Pla2g2a prevents tumorigenesis in Muc2-deficient mice. American Association for Cancer Research Mouse Models of Cancer Meeting, Cambridge, MA, (October, 2006).

McAlpine, C.A., Barak, Y., Matise, I., and Cormier, R.T. (2006).   Intestinal-specific PPARg deficiency enhances tumorigenesis in Apc ^Min/+ mice.  Wisconsin Symposium on Human Biology, Madison, WI.

McAlpine, C.A., Barak, Y., and Cormier, R.T. (2005). Intestinal-specific PPARg deficiency enhances tumorigenesis in Apc ^Min/+ mice. The 19^th Annual International Mouse Genome Conference, Strasbourg, France.

Fijneman, R.J.A., Cormier, R.T., Meijer, G.A., and Kraal, G. (2004). Is Group IIA Secretory Phospholipase A2 a Candidate Gene for Marif1? American Association for Cancer Research Meeting on Colon Cancer in Murine Models and Humans, Bar Harbor, ME.

Bogan, C., McAlpine, C., Amdahl, M., Bluemn, E., Velcich, A., Barak, Y., Evans,  R., Chen, J., and Cormier, R. (2004). Genetic Pathway Analysis of Mom1 Candidate Genes. The 18^th Annual International Mouse Genome Conference, Seattle, WA.

Bogan, C., McAlpine, C., Amdahl, M., Bluemn, E., Velcich, A., Barak, Y., Evans,  R., Chen, J., and Cormier, R. (2004). Genetic Pathway Analysis of Mom1 Candidate Genes. American Association for Cancer Research Meeting on Colon Cancer in Murine Models and Humans, Bar Harbor, ME.

Dove, W.F., Amos-Landgraf, J., Bilger, A., Chen, X., Clipson, L., Cormier, B., Ernhardt, W., Haigis, K., Halberg, R., Harms, A., Hegeman A., Hoff, P., Kwong, L., Meyerand, E., Nelson, C., Newton, M., Pasch, C., Shedlovsky A., Sussman, M., Thliveris, A., Weichert, J., and White, A. (2004). From the Apc-Min Mouse Model to Genes and Moleculaes Involved in Human Colon Cancer. American Gastroenterological Association Research Symposium, New Orleans, LA.

Haigis, K.M., Cormier, R.T., Shoemaker, A.R., and Dove, W.F. (2001). Spontaneous and Induced Mechanism of Apc Loss During Intestinal Tumor Initiation. Aspen Cancer Conference, Aspen, Colorado.

Enerson, B.E., Cormier, R.T., and Drewes, L.R. (2001). Influence of the Ketogenic Diet on Gene Expression Profiles of Rat Cerebral Cortex. University of Minnesota Biomedical Genomics Center Conference, Minneapolis, MN.

Enerson, B.E., Cormier, R.T., and Drewes, L.R. (2001). Generation of a Transgenic Mouse Over Expressing MCT1 in the Brain Endothelium. IVth International Conference, Cerebral Vascular Biology, King’s College, Cambridge, UK.

Dove, W.F., Bilger, A., Cormier, R.T., Gould, K.A., Haigis, K.M., Halberg, R.B., Shedlovsky, A., and Shoemaker, A.R. (2000). The Network of Genes Impacting Intestinal Neoplasia. The 14^th International Mouse Genome Conference, Narita, Japan.

Cormier, R.T.  Pla2g2a and Mom1:  A Complex Story (2000). Conference on Modeling Human Colo-Rectal Cancer in Mice, The Jackson Laboratory, Bar Harbor, ME.

Cormier, R.T.  The Dnmt1 ^N/+ Allele:  An Effect on Min Tumor Growth Kinetics and Synergy with Mom1 (2000). Conference on Modeling Human Colo-Rectal Cancer in Mice, The Jackson Laboratory, Bar Harbor, ME.

Cormier, R.T., Halberg, R.B., and Dove, W.F.  The Effects of DNA Hypomethylation on Tumorigenesis in the B6-Min Mouse (1999). Symposium: Genetics, Genomics, and Molecules, University of Wisconsin-Madison.

Cormier, R.T., Halberg, R.B., Merritt, A.J., Hong, K.H., Hawkins, T.L., Richardson, P., Mulherkar, R., Lander, E.S., and Dove, W.F. (1998). The Role of Secretory Phospholipase Pla2g2a in Resistance to Min-induced Intestinal Tumorigenesis.    Keystone Symposia on Signal Transduction and Lipid Second Messengers.  Taos, NM.

Cormier, R.T., and Dove, W.F.  Investigations Into the Role of DNA Methyltransferase Deficiency in Min Tumorigenesis (1997). FASEB Conference on Biological Methylation, Saxton’s River, VT.

Selected Scientific Meeting Presentations

VU Medical Center Amsterdam, Netherlands. (2005). Seminar presentation, Dept. of Pathology. “Intestinal-specific PPARg deficiency enhances tumorigenesis in Apc ^Min/+ mice.”

Lakehead University Seminar Series on Biotechnology, Thunder Bay, ON, Canada. (2005). “Genetic Analysis of Mom1 Intestinal Cancer Resistance Genes”.

American Association for Cancer Research Meeting on Colon Cancer in Murine Models and Humans, The Jackson Laboratory, Bar Harbor, ME. (2004). “Genetic Pathway Analysis of Mom1 Candidate Genes”.

University of Minnesota Department of Biochemistry, Molecular Biology & Biophysics Seminar Series, Minneapolis, MN. (2003). “Genetic Analyis of the Mom1 Locus”.

University of Minnesota Cancer Center, Genetic Mechanisms of Cancer Seminar Series, Minneapolis, MN. (2003). “Genetic Analysis of the Mom1 Locus”.

Modeling Human Colo-Rectal Cancer in Mice, The Jackson Laboratory, Bar Harbor, ME. (2000).  “Pla2g2a and Mom1: a Complex Story.”

Modeling Human Colo-Rectal Cancer in Mice, The Jackson Laboratory, Bar Harbor, ME. (2000).  “The Dnmt1 ^N/+ Allele: an Effect on Min Tumor Growth Kinetics and Synergy with Mom1.”

Roswell Park Cancer Institute, Molecular Genetics Seminar Series, Buffalo, NY. (1998). “The Role of Dnmt1 in Min Tumorigenesis”.

FASEB Conference on Biological Methylation. Saxton’s River, VT. (1997).  “Investigations Into the Role of DNA Methyltransferase Deficiency in Min Tumorigenesis.”