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Pioneer of Cancer Biology To Give Khoury Lecture

By Samuel Perdue

Bad things can happen when cells stop paying attention to their growth signals. When cells break from the tightly regulated balance of reproduction and death, uncontrolled division results and cancer may occur. On Wednesday, Dec. 6, a pioneer in the field of cancer biology will visit NIH and speak about how far science has come in understanding the underlying mechanisms behind cell division and cancer.

Dr. Robert A. Weinberg will present "Creation of Human Cancer Cells" for the annual George Khoury Lecture, to be held at 3 p.m. in Masur Auditorium, Bldg. 10. Weinberg, who is currently Daniel K. Ludwig professor for cancer research at the Massachusetts Institute of Technology, has achieved many "firsts" in cancer research, and his studies have continued to reveal new ways of looking at human cancer and its causes.

Dr. Robert A. Weinberg

In 1980, Weinberg's laboratory broke new ground in cancer research with the discovery of the first human oncogene, called ras. The ras oncogene is a mutated form of a gene encoding an intracellular switch. In healthy cells, this protein switch turns cell division on and off, providing a key control point that governs cell numbers. When the gene is altered, however, the switch remains stuck in the "on" position, causing the cell to divide out of control.

Weinberg continued to look for ways in which altered genes could affect cell division, and in 1986 his studies of retinal cancer led to isolation of the first known tumor suppressor gene. The retinoblastoma gene, or Rb, encodes a protein that puts the brake on cell division. Many children with retinoblastoma are missing their Rb gene and therefore cannot stop cell division in certain retinal cells, causing tumors to appear.

Those seminal discoveries, made within a span of 6 years, identified two types of cellular controls that, when altered, could lead to cancer in humans. Weinberg's research revolutionized the way scientists thought about human cancer and led to new methods of early diagnosis. By beginning to establish a framework for the underlying genetics of cancer, the Weinberg laboratory opened the door for many other researchers to begin probing cells for other genes that might play a role in this disease.

Over the years many new oncogenes and tumor suppressors have been discovered, and Weinberg has continued to investigate the complex molecular circuitry that controls cell division. Today his laboratory also studies a third protein, called telomerase, which has been implicated in many human cancers. Telomerase extends the tips of chromosomes that have been shortened following repeated cell divisions. These shortened tips, or telomeres, typically tell a cell when it has reached the end of its life. Telomerase blocks the signal, however, and the cell continues to divide unchecked.

"Over the past two years, we have learned how alterations of oncogenes, tumor suppressor genes, and the telomerase gene collaborate to produce cancerous cells," says Weinberg. "Such work suggests that a common set of regulatory pathways must be perturbed during the creation of a wide variety of human tumor types."

Weinberg has been on the MIT biology faculty since 1972, and in 1982 he became one of the five original members of the Whitehead Institute for Biomedical Research, a position he still holds today. He has been an American Cancer Society research professor since 1985. A member of the National Academy of Sciences, he holds many honors and awards including the Discover magazine 1982 Scientist of the Year, the National Academy of Sciences/U.S. Steel Foundation Award in molecular biology, the Bristol-Myers Award for Distinguished Achievement in Cancer Research, the Gairdner Foundation International Award for Achievement in Medical Science, and the 1997 Medal of Science. He has served on scientific advisory boards for the Institute of Molecular Pathology in Vienna, Austria; the Weizmann Institute in Rehovot, Israel; and Massachusetts General Hospital.

Weinberg is the author or editor of five books and more than 290 articles. His most recent books, intended for lay audiences, 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, coauthored with former NIH director Dr. Harold Varmus.

The talk is part of the NIH Director's Wednesday Afternoon Lecture Series. For more information or for reasonable accommodation, call Hilda Madine, 594-5595.

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