Robert A. Weinberg, PhD

2007-2008 BCRF Project:
The ability of breast cancer cells to thrive and proliferate at various locations throughout the human body depends on their ability to recruit normal supporting (stromal) cells from the bone marrow. This recruitment depends on the ability of the breast cancer cells to stimulate the bone marrow to release such supporting cells into the circulation, making them available for recruitment by the breast cancer.

Dr. Weinberg's laboratory has discovered one of the signals that primary breast tumors release to stimulate the bone marrow. They would like to determine over the next year the nature of the cells in the bone marrow that are stimulated by this signal and mobilized into the circulation as well as the identities of the support (stromal) cell types that are recruited from the circulation into the tumor-associated stroma. The ability of the cancer cells in a primary breast tumor to metastasize is influenced by one type of bone marrow cell, which is recruited into the tumor mass and, once present, stimulates the breast cancer cells to move actively and metastasize. They would like to know the identity of the signal(s) that are released by breast cancer cells and impinge upon nearby recruited bone marrow-derived stromal cells, inducing the latter to release invasion/metastasis-provoking signals within the primary breast tumor mass.

Mid-Year Progress Report:
The ability of breast cancer cells to invade and metastasize depends on their acquisition of traits that are normally associated with mesenchymal cells, i.e., cells from connective tissues. Cells that undergo such a change in property are often said to have undergone an "epithelial-mesenchymal transition" (EMT), which imparts to breast cancer cells traits such as motility, invasiveness and a resistance to killing. Dr. Weinberg's team now has found, quite unexpectedly, that another consequence of breast cells passing through an EMT is the acquisition of many cellular traits that are normally associated with stem cells. Thus, normal human mammary epithelial cells, of the type that line the milk ducts, acquire stem-cell traits when they undergo an EMT, as do human breast cancer cells. This holds important implications for diagnosing and treating human breast cancers, since the curing of breast tumors will likely depend on eradicating all of their cancerstem cells.

Bio:
Dr. Weinberg is a founding member of the Whitehead Institute for Biomedical Research and the Daniel K. Ludwig Professor for Cancer Research at the Massachusetts Institute of Technology (MIT). He is also the first Director of the Ludwig Cancer Center at MIT. He is an internationally recognized authority on the genetic basis of human cancer.

Dr. Weinberg and his colleagues isolated the first human cancer-causing gene, the ras oncogene, and the first known tumor suppressor gene, Rb, the retinoblastoma gene. The principal goal of his research program is to determine how oncogenes, their normal counterparts (proto-oncogenes), and tumor suppressor genes fit together in the complex circuitry that controls cell growth. More recently, his group has succeeded in creating the first genetically defined human cancer cells. He is particularly interested in applying this knowledge to improve the diagnosis and treatment of breast cancer.

Dr. Weinberg is the author or editor of six books and more than 350 articles. He has written a comprehensive cancer textbook entitled "The Biology of Cancer". His other books, intended for a lay audience, are "One Renegade Cell," "Racing to the Beginning of the Road: The Search for the Origin of Cancer" and "Genes and the Biology of Cancer," co-authored with Dr. Harold E. Varmus, former Director of the National Institutes of Health. He is an elected Member of the U.S. National Academy of Sciences and Fellow of the American Academy of Arts and Sciences. He is a Member of the American Philosophical Society and the Institute of Medicine.

Among Dr. Weinberg's many honors and awards are the Discover Magazine 1982 Scientist of the Year, the National Academy of Sciences/U.S. Steel Foundation Award in Molecular Biology, the Sloan Prize of the General Motors Cancer Research Foundation, the Bristol-Myers Award for Distinguished Achievement in Cancer Research, the Harvey Prize from the American Society for Technion Israel Institute of Technology, the Gairdner Foundation International Award, the Keio Medical Foundation Prize, the 1997 National Medal of Science, the City of Medicine Award and the 2004 Wolf Foundation Prize and the Prince of Asturias Science Prize. He has served on scientific advisory boards for the Institute of Molecular Pathology in Vienna, Austria, the Weizmann Institute in Rehovot, Israel, and the Massachusetts General Hospital in Boston.

Born in Pittsburgh in 1942, Dr. Weinberg received his B.S. (1964) and Ph.D. (1969) degrees in Biology from MIT. He did postdoctoral research at the Weizmann Institute and the Salk Institute in La Jolla, California, and then returned to MIT in 1972. In 1982, he was appointed Professor of Biology at MIT.