Yamanaka Wins 2012 Nobel Prize in Medicine

Shinya Yamanaka, MD, PhD, a professor of anatomy at UCSF as well as a senior investigator at the university-affiliated Gladstone Institute for Cardiovascular Disease, was awarded the 2012 Nobel Prize in Physiology and Medicine on Monday “for the discovery that mature cells can be reprogrammed to become pluripotent.”

Yamanaka, 50, whose primary academic appointment is at Kyoto University in Japan, shares the award with Sir John B. Gurdon, 79, of the University of Cambridge.

“This is a wonderful day for Dr. Yamanaka, UCSF, the Gladstone Institute, Kyoto University and the world,” said Chancellor Susan Desmond-Hellmann. “Dr. Yamanaka’s work exemplifies the potential of basic research to transform our understanding of human cell and molecular biology, and to use this knowledge to work toward the development of treatments for currently intractable diseases. He has opened up a whole new field of discovery, and our scientists are working hard to advance the research.”

Dr. Yamanaka came to UCSF by way of a postdoctoral fellowship in 1993, after completing his MD, orthopedic surgery residency and PhD in Japan. During his stay in San Francisco from 1993-1996, he researched the metabolism of cholesterol and fat at the Gladstone Institutes.

“The project he undertook was a complete failure,” said Robert Mahley, president emeritus and founder of the Gladstone Institutes. “Undaunted, he wanted to know why the cells proliferated as they did, and one of the ways to get to the answer was to study embryonic stem cells.” After completing his fellowship, Dr. Yamanaka returned to Japan, where he conducted the research that led to his seminal series of papers published in Nature and Cell in 2006 and 2007, describing a process of “resetting” adult cells into an embryonic-like state.

The majority of adult cells are differentiated, capable of making more copies of themselves but not of other types of cells. By contrast, human embryonic stem cells are known to be pluripotent, which means that they have the potential to become almost any cell in the human body. While these properties hold significant promise for many fields in medicine and science, the use of human embryos in the United States has been fraught with controversy.

Yamanaka’s work bypassed this dilemma by figuring out that by adding just four genes (now known as Yamanaka factors) to the adult skin cells of mice, he could prod them back into a pluripotent state, capable of developing into virtually any other type of cell. He called these discoveries “induced pluripotent stem cells,” or iPS cells for short. 

Although research into the clinical applications of iPS cells is still in its early stages, scientists at UCSF have been investigating their uses in a variety of different projects in regenerative medicine, drug safety and personalized medicine. On Monday, Dr. Yamanaka’s colleagues at UCSF cited these numerous potential applications in their congratulatory statements, emphasizing how far his discoveries have broadened the medical horizon.

“The ability to bring cells back to their more pluripotent state has generated an industry of investigators who are exploring the potential of this approach for therapies for neurological conditions, while simultaneously using this technology to develop new model systems from the peripheral cells of patients,” said Dr. Bruce Miller, chair of the UCSF Department of Neurology. “This discovery represented one of the few remaining holy grails in science, and it will change our field forever.”