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Miracles in the Making


By Mary Daily

Published Jan 1, 2011 8:00 AM

Four Genes Equal One Breakthrough

The most hopeful expectations lie in regenerative medicine — the creation of healthy cells to replace damaged or destroyed ones.

"It's the ability to remake what is damaged and replace what is lost," Witte explains, calling regenerative medicine "a game changer ... We're pushing the envelope because we know we can make a difference."

He cites Alzheimer's, Parkinson's and heart diseases as among those that lend themselves to this type of therapy.

But politics has roiled the lab for as long as there has been stem cell science. The use of human ES cells remains a political flashpoint, with controversy constantly impinging on the science and limiting researchers' access to human ES cells (most recently in August, when a federal judge blocked President Barack Obama's 2009 executive order expanding human ES cell research). So it has long been clear that a viable alternative was needed to keep the science moving.

The answer began to emerge in 2006, when a researcher in Kyoto, Japan, inserted into the genome of adult mouse skin cells four genes that are typically highly expressed in embryonic stem cells. The result was induced pluripotent stem cells, or iPS cells, which are highly similar to ES cells. Here was the viable alternative — and here again, UCLA would play a pivotal role.

At about the same time as the Japanese researchers were making their discovery, biochemist Kathrin Plath and molecular and cellular biologist Bill Lowry joined Witte's team.

Plath, who grew up in Germany, attended Harvard Medical School and, following postdocs at MIT and UC San Francisco, joined the faculty of UCLA's medical school.

Lowry, from Seattle, attended the University of Washington and the Weill Cornell Graduate School of Medical Sciences in New York, where he studied how cells communicate with one another, called cell signaling. At Rockefeller University, his postdoctoral studies focused on how stem cells translate signals from their environment into a coherent response. Now, on UCLA's life sciences faculty in the College of Letters & Science, Lowry teaches undergraduates in addition to running his lab.


Image provided the Broad Stem Cell Research Center.

Building on the Japanese discovery, Plath and Lowry — through several attempts — made a huge breakthrough: By using the same four genes, they produced iPS cells from an adult human skin cell. It was a seminal leap in regenerative medicine.

"If we can take a skin cell back into an embryonic state," Plath explains, "we can override what was set up in development."

Plath and Lowry were the first in California to make the discovery, and it would not have been possible without first knowing how to successfully grow human ES cells in the lab.

The team has now created about 50 iPS lines for future use.