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Today, his lab focuses on the molecular mechanisms behind tumor formation. Weinberg’s research is divided into three main areas: invasion and metastasis; cell death; and the processes by which epithelial and stromal cells, the two primary types of cells found in mammalian tissue, interact in tumors [ weinberg research 220 kbps QuickTime].
Weinberg considers metastasis and invasion to be the "last frontier of cancer research", since researchers know very little about how tumors manage to colonize distant sites in the body. He is focusing on a small group of transcription factors proteins that control gene expression. These proteins, which are typically involved in embryogenesis, may contribute to a cancer’s ability to colonize distant sites in the body. Weinberg and his team are exploring the theory that tumors can resurrect the embryonic properties of these proteins and use them to seed the body with cancer cells.
Each time a cell divides into two new daughter cells, a small protective region of the chromosomes called the telomere loses some of its DNA. When a particular amount of the telomere is gone, the cell dies. Cancer cells, however, develop the ability to preserve this region and then can replicate without limit. Weinberg’s lab is exploring the molecular events involved in this process.
Most mammalian tissues are formed in distinct epithelial and stromal layers. Often, a tumor that forms in an epithelial tissue layer must recruit stromal cells in order to become a carcinoma, and Weinberg’s lab is exploring the molecular process by which this occurs. In addition, his lab is investigating a pathway within epithelial cells that enables them to release signals that stimulate blood vessel growth in nearby stromal cells. Weinberg’s group has also developed a technique for incorporating human epithelial cells into mouse breast tissue so that the mice form human breast tissue, and even human breast cancer.
Weinberg, who received his PhD in biology from the Massachusetts Institute of Technology in 1969, has held research positions at the Weizmann Institute and the Salk Institute. In 1982, Weinberg helped found Whitehead Institute, joined the faculty as a professor of biology at MIT, and published his landmark paper "Mechanism of Activation of a Human Oncogene" in the journal Nature. In 1999, another major paper, "Creation of Human Tumor Cells with Defined Genetic Elements," was also published in Nature.
Selected Publications
Gupta, P.B., Kuperwasser, C., Brunet, J.P., Ramaswamy, S., Kuo, W.L., Gray, J.W., Naber, S.P., Weinberg, R.A. (2005) The melanocyte differentiation program predisposes to metastasis after neoplastic transformation. Nature Genetics, 37, 1047-1054.
Yang, J., Mani, S.A., Donaher, J.L., Ramaswamy, S., Itzykson, R.A., Come, C., Savagner, P., Gitelman, I., Richardson, A., Weinberg, R.A. (2004). Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell, 117: 927-939
Hahn, W.C., Counter, C.M., Lundberg, A.S., Beijersbergen, R.L., Brooks, M.W., and Weinberg, R.A. (1999). Creation of human tumor cells with defined genetic elements. Nature, 400:464-468.
Land, H., Parada, L.F., and Weinberg, R.A. (1983). Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature, 304: 596-602.
Tabin, C.J., Bradley, S.M., Bargmann, C.I., Weinberg, R.A., Papageorge, A.G., Scolnick, E.M., Dhar, R., Lowy, D.R., and Chang, E.H. (1982). Mechanism of activation of a human oncogene. Nature, 300: 143-149.
Shih, C. and Weinberg, R.A. (1982). Isolation of a transforming sequence from a human bladder carcinoma cell line. Cell, 29: 161-169. |
