The Professional Career of Shinya Yamanaka, 2012 Nobel Prize Awardee by John Diaz

Shinya Yamanaka is a Japanese physician and researcher of adult stem cells, or biological cells found in all multicellular organisms, that can divide through mitosis and differentiate into diverse specialized cell types and can self-renew to produce more stem cells.

Yamanaka serves as the director of Center for iPS Cell Research and Application and a professor at the Institute for Frontier Medical Sciences at Kyoto University, or “Kyodai,” a national university located in Kyoto, Japan; and as a professor of anatomy at University of California, San Francisco (UCSF), a center of health sciences research, patient care, and education, located in San Francisco, California. He is also the current president of the International Society for Stem Cell Research (ISSCR).

In 2011, he received the Wolf Prize in Medicine, awarded once a year by the Wolf Foundation in Israel, with Rudolf Jaenisch, a biologist at MIT. This year, he won two prizes: the Millenium Technology Prize, the largest technology prizes in the world, together with Linus Torvalds, a Finnish American software engineer and hacker, who has the principal force behind the development of the Linux kernel; and the Nobel Prize in Physiology or Medicine, administered by the Nobel Foundation, awarded once a year for outstanding discoveries in the fields of life sciences and medicine, together with John B. Gurdon.

Between 1987 and 1989, Yamanaka was a resident in orthopedic surgery at the National Osaka Hospital. From 1993 to 1996, he was at the Gladstone Institute of Cardiovascular Disease, an independent and nonprofit biomedical research organization whose focus is to better understand, prevent, treat and cure cardiovascular, viral and neurological conditions such as heart failure, HIV/AIDS and Alzheimer’s disease; which is affiliated with the University of California, San Francisco (“UCSF”), a center of health sciences research, patient care, and education, located in San Francisco.

Between 1996 and 1999, he was an assistant professor, which is generally a rank held for a probationary period of three to seven years, after which the individual must either earn tenure and promotion to associate professor or find other employment, at the Nara Institute of Science and Technology, abbreviated as NAIST, a Japanese national university located in Ikoma, Nara of Kansai Science City. During 2003-2005, he was a professor at the Nara Institute of Science and Technology. Between 2004 and 2010, Yamanaka was a professor at the Institute for Frontier Medical Sciences. Currently, Yamanaka is the director and a professor at the Center for iPS Cell Research and Application in Kyoto University, Japan.

In 2006, he and his team induced pluripotent stem cells (iPS cells), a type of pluripotent stem cell artificially derived from a non-pluripotent cell--typically an adult somatic cell--by inducing a “forced” expression of specific genes, from adult mouse fibroblasts, a type of cell that synthesizes the extracellular matrix and collagen, the structural framework (stroma) for animal tissues, and plays a critical role in wound healing.

iPS cells closely resemble embryonic stem cells (“ES cells”), pluripotent stem cells derived from the inner cell mass of the blastocyst, an early-stage embryo, the “in vitro” equivalent of the part of the blastocyst, a structure formed in the early development of vertebrates (the embryo a few days after fertilization), which grows to become which the embryo proper. They could show that his iPS cells were pluripotent, which in cell biology, refers to a stem cell that has the potential to differentiate into any of the three germ layers: endoderm (interior stomach lining, gastrointestinal tract, the lungs), mesoderm, (muscle (muscle, bone, blood, urogenital), or ectoderm (epidermal tissues and nervous system); i.e. capable of generating all cell lineages of the body, and were soon after capable of generating mice from iPS cells.

In 2007, he and his team generated iPS cells from human adult fibroblasts, again as the first group to do so. A key difference from previous attempts by the field was his team’s use of multiple transcription factors (sometimes called a sequence-specific DNA-binding factor), which in molecular biology and genetics, is a protein  that binds to specific DNA sequences, thereby controlling the flow (or transcription) of genetic information from DNA to mRNA. It is instead of transfecting, or the process deliberately introducing nucleic acids into cells, one transcription factor per experiment.

They started with 24 transcription factors known to be important in the early embryo, but could in the end reduce it to four transcription factors--SoX2, also known as “SRY (sex determining region-Y)-box 2, a transcription factor that is essential for maintaining self-renewal and pluripotency, of undifferentiated embryonic stem cells; Oct4 (octamer-binding transcription factor 4), also known as “POU5F1” (POU domain, class 5, transcription factor 1), a protein that in humans is encoded by the “POU5F1” gene; Klf4 (“Kruppel-like factor 4”), a protein that in humans is encoded by the “KLF4” gene; and, c-Myc (“Myc”), a regulator gene that codes for a transcription factor.

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