Our research efforts are focused on investigating select mechanisms by which oncogenes disrupt cell growth, proliferation and apoptosis. Our emphasis is currently on understanding how the oncoproteins c-myc, and the large and small T antigen transforming proteins of the DNA tumor virus SV40, impact specific signal transduction pathways that regulate cellular homeostasis. Signaling modules that we are investigating include the TGF-? and PI3K/Akt/mTOR pathways, both of which are disrupted at multiple nodes in a variety of human cancers. Our research strategy utilizes a cadre of mouse strains with select, conditional gain- and loss-of-function mutations in the TGF-? and PI3K/Akt signaling pathways. These strains of mice are being used independently, or in combination with mouse strains expressing dominant oncogenes either conditionally or constitutively, to address the specific contribution of these pathways to the loss of growth control and the generation of cancer. A second area of interest is the extension of gene inactivation technology to the rat. To date there are no reports of the successful isolation and propagation of pluripotent embryonic stem cell lines in this species. The strategies we are currently employing include using in-house generated strains of genetically engineered rats which harbor GFP-marked embryonic stem cells and germ cells, in combination with novel cell culture and cell sorting strategies. Once established, pluripotent rat ES cell lines will be used for the inactivation of select genes via homologous recombination.
RESEARCH INTERESTS
Regulation of growth and proliferation
In vivo models of cancer
Oncogene and growth factor collaboration in cancer
Regulation of liver growth
RECENT PUBLICATIONS
Comerford, S.A., Clouthier, D.E., Hinnant, E., and Hammer, R.E., "Induction of hepatocyte proliferation and death by modulation of T-Antigen expression." Oncogene, 22:2515-2530, 2003
Clouthier, D.E., Comerford, S.A., and Hammer, R.E., "Hepatic fibrosis, glomerulosclerosis, and a lipodystrophy-like syndrome in PEPCK-TGF-beta1 transgenic mice." J. Clin. Invest., 100:2697-2713, 1997
Engelking, L.J., Kuriyama, H, Hammer, R.E., Horton, J. D., Brown, M.S.,Goldstein, J. L. and Liang, G, "Overexpression of Insig-1 in the livers of transgenic mice inhibits SREBP processing and reduces insulin-stimulated lipogenesis" J. Clinical Investigation, 113:1168-75, Spring 2004
Horton, J. D., Shiomorura, I., Ikemoto, S.,Bashmakov, Y., and Hammer, R.E., "Overexpression of sterol regulatory element-binding protein 1a in mouse adipose tissue produces adipocyte hypertrophy, increased fatty acid secretion, and fatty liver" J. Biological Chemistry, 278:36652-60, 2003
Beale, E.G., Forest, C., and Hammer, R.E., "Regualtion of cytosolic phosphoenolpyruvate carboxykinase gene expression in adipocytes" Biochimie, 85:1207-11, 2003
SIGNIFICANT PUBLICATIONS
Hofmann, S.L., Russell, D.W., Brown, M.S., Goldstein, J.L., and Hammer, R.E., "Overexpression of low density lipoprotein (LDL) receptor eliminates LDL from plasma in transgenic mice." Science, 239:1277-1281, 1988
Hammer, R.E., Maika, S.D., Richardson, J.A., Tang, J.P., and Taurog, J.D., "Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human beta 2m: an animal model of HLA-B27-associated human disorders." Cell, 63:1099-1112, 1990
Palmiter, R.D., Brinster, R.L., Hammer, R.E., Trumbauer, M.E., Rosenfeld, M.G., Birnberg, N.C., and Evans, R.M., "Dramatic growth of mice that develop from eggs microinjected with metallothionein-growth hormone fusion genes." Nature, 300:611-615, 1982
Hammer, R.E., Palmiter, R.D., and Brinster, R.L., "Partial correction of murine hereditary growth disorder by germ-line incorporation of a new gene." Nature, 311:65-67, 1984
Hammer, R.E., Brinster, R.L., Rosenfeld, M.G., Evans, R.M., and Mayo, K.E., "Expression of human growth hormone-releasing factor in transgenic mice results in increased somatic growth." Nature, 315:413-416, 1985
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