Hidesaburo Hanafusa Biography (1929-)
- virologist, molecular oncologist
Hidesaburo Hanafusa is a prominent researcher in the genetics of cancerous viruses. As explained by Fulvio Bardossi and Judith N. Schwartz in a Research Profile distributed by the Rockefeller University, Hanafusa "has used his training as a biochemist, combined with new insights and new technologies from molecular biology and genetics, to observe, isolate, control, and explain the events that occur and the elements that interact when virus meets cell." Hanafusa's early work with the Rous sarcoma virus (RSV), a virus that causes cancer in birds, has laid the foundation for a new hypothesis on how cancer may be caused by damaged genes--so-called "oncogenes"--within an organism's own cells. The oncogene theory proposes that genes have the potential to cause a normal cell to become cancerous. Hanafusa's current investigations at the Rockefeller University in New York City focuses on oncogenesand explores how they induce cellular transformation from a normal to a cancerous state.
Hanafusa was born on December 1, 1929 in Nishinomiya, Japan. He is the son ofKamehachi and Tomi Hanafusa. He majored in biochemistry, and received his bachelor's degree in 1953, and his doctorate in 1960, both from Osaka University. On May 11, 1958, Hanafusa married Teruko Inoue, a fellow student at Osakawho has become one of his principal scientific colleagues. The couple have one daughter, Kei. In 1961, Hanafusa left his homeland in Japan and accepted aposition in the laboratory of Harry Rubin, a pioneer in tumor virus researchat the University of California in Berkeley.
When Nobel Prize-winning pathologist Peyton Rous made the pioneering discovery in 1910 that a virus causes cancer in chickens, the basic mechanismsof cancer were as yet poorly understood. A half century later, Hanafusa continued the research into the causes of viral cancer. Hanafusa's initial project with Rubin at the University of California produced a major discovery. While trying to isolate pure RSV, the researchers found that the virus could transform normal cells into cancerous ones. Interestingly, however, the virus could not replicate itself without a protein from a helper virus. This virus became a tool for future experiments. By changing the properties and activitiesof the altered RSV, Hanafusa could analyze key reactions that are responsiblefor bringing about a cancerous state. Hanafusa pursued these studies as a visiting scientist at the College de France in Paris from 1964 to 1966 and thenas head of a laboratory of viral oncology at the Public Health Research Institute in New York City.
In 1973 Hanafusa became professor of viral oncology at the Rockefeller University. In a new set of experiments, he injected chickens with RSV that had been altered to remove most of the genetic information specifically responsiblefor tumor formation. To his surprise, the chickens developed tumors anyway. On examination, he found the viruses had reacquired the missing tumor gene--the oncogene--from the chicken cell's own genetic information. These experiments showed that inappropriate activation of normal cellular genes causes tumors. Since then, more than twenty such oncogenes have been identified as being responsible for various kinds of cancers.
While exploring the nature of the RSV sarcoma gene (an oncogene), Hanafusa learned that the RSV mutants which he had isolated were temperature sensitive.This proved to be an important clue that the substance produced was a protein. Subsequent speculations presume that oncogenes may have an important role in normal cell life--to manufacture a protein required by the cell. It is onlywhen the protein is overproduced that cancer occurs. Hanafusa later learnedthat the RSV sarcoma gene induces the protein tyrosine kinase, which can, byitself, trigger a cell division. Further investigations by Hanafusa have explored the role of this protein in the cell's signaling apparatus, a complicated sequence of intracellular communication known as phosphorylation. Hanafusafound that when infected with RSV, many cellular proteins become phosphorylated on tyrosine, and this process is associated with changes in cell growth.
In 1988, Hanafusa identified a novel oncogene, crk, in an avian sarcoma virus. Although it has no known catalytic function, its overproduction induces tyrosine phosphorylation of some cellular proteins and causes cancer. This finding has contributed to a surge of interest in the interaction between the phosphotyrosine-containing proteins and peptide domains in the cell's signaling network.
For his contributions in cancer virus studies, Hanafusa received the Howard Taylor Ricketts Award in 1981, the Albert Lasker Basic Medical Research Awardin 1982, the Asahi Press Prize in 1984, and the Alfred P. Sloan, Jr. Prize in1993. He was elected a Foreign Associate of the National Academy of Sciencesin 1985.