Marius Wernig arrived at Stanford recently with a worldwide reputation for creating induced pluripotent stem cells from adult skin cells. What is less known is his success in composing classical music and opera, with pieces having premiered in Bonn, Cologne and Vienna.

"The two fields have a lot of parallels," said Wernig, who in December became assistant professor of pathology at the University School of Medicine. "Both require creativity, and are yet highly structured. Composing operates with a set of rules, or tonal system, while biological research utilizes sets of common experiments to explore various hypotheses."

Wernig, who had previously been at MIT's Whitehead Institute, will be a key member of the Stem Cell Biology and Regenerative Medicine Institute. His appointment is the latest in assembling a "dream team" for stem cell research at the institute, covering all of the most promising areas of stem cell research.

"With the hiring of Dr. Wernig, we now have outstanding people pursuing research along the most exciting scientific fronts: embryonic stem cells, cancer stem cells, mature tissue and organ stem cells and now induced pluripotent stem cells," said the institute's director, Irving Weissman, the Virginia & D.K. Ludwig Professor for Clinical Investigation in Cancer Research. "The extensive talents of these scientists and the development of the Lorry I. Lokey Stem Cell Research Building set the stage for major advances in this field."

Agreed Renee Reijo-Pera, PhD, director of the institute's Center for Human Embryonic Stem Cell Research and Education. "He brings expertise in both iPS cells and in neural biology, which is something we didn't previously have at the institute."

Born in Innsbruck, Austria, Wernig studied medicine and music in Vienna and Germany before pursuing a research career at the Whitehead Institute in Massachusetts. There, Wernig worked in the laboratory of Rudolf Jaenisch, MD, one of the few research groups worldwide to successfully create iPS cells from mouse skin cells. The researchers discovered that, by introducing just four genes into an adult cell, they could induce that cell to behave like an embryonic stem cell. Althoughresearch on iPS cells holds the promise of creating stem cell therapies without the use of embryos, researchers emphasize that there are technical challenges associated with iPS cells and they need to follow all research pathways to provide the greatest chance of success.

Wernig's research will be aimed at understanding how iPS reprogramming works. "Right now it's a bit of a black box," Wernig said. "We know that if we stick these four genes into the cell it undergoes this amazing metamorphosis, but how that really works is completely unclear."

The second major part of Wernig's research will be to look at how iPS cells might be used to treat disease. Wernig said that using embryo-derived stem cells in therapy would face significant logistical hurdles. Creating new stem cells with a particular patient's genetic makeup by nuclear transfer (often called therapeutic cloning) would involve implanting adult cell nuclei into oocytes (egg cells). Because the success rate is currently so low in the animal models being tested, hundreds of oocytes have to be harvested to create one patient-specific stem cell line. Nuclear transfer hasn't yet been achieved in humans. "Logistically it would be very difficult," Wernig observed. The iPS technique offers the hope that patient-specific stem cells could be easily created by transforming skin or other cells that can be easily obtained without the use of eggs and thereby bypassing all ethical considerations and technical hurdles associated with therapeutic cloning.

Wernig plans to focus on two major diseases that may yield to stem cell therapy: sickle cell anemia and Parkinson's. In sickle cell disease, a genetic mutation can sometimes make red blood cells change shape, which can cause pain, organ damage and other complications. Stem cell research may provide a way to create new blood cells without the genetic mutation, diminishing or eliminating symptoms of the disease. Parkinson's disease is a slowly progressive movement disorder caused by the loss of a very specific population of nerve cells in the brain. If a patient's own cells can be transformed into embryonic cells that grow into replacements for those nerve cells, the patient's movements can improve.

"We can't say that we will cure Parkinson's disease, but I'm very optimistic that these patients would greatly benefit" from a stem cell therapy, Wernig said.

 

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