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New senior associate dean for research building bridges from bench to bedside

Courtesty of Daria Mochly-Rosen

Daria Mochly-Rosen became the medical school’s new senior associate dean for research in late November.

BY RUTHANN RICHTER

One of the defining moments of Daria Mochly-Rosen's career came in the summer of 1998, when she was sitting in a chapel in Florence, Italy, working on a large computer beneath a 16th-century fresco. The church had been converted to a magnetic resonance laboratory, and Mochly-Rosen, PhD, was doing computer simulations to pinpoint the part of an enzyme thought to have a key role in heart disease.

Suddenly, the answer became clear. Her finding, confirmed the same day by her labmates at Stanford, would lead to a drug that is now in a clinical trial to reduce damage from heart attacks.

"For me, the breakthroughs always happened when I was out of my element," said Mochly-Rosen, professor of molecular pharmacology and the George D. Smith Professor in Translational Medicine. "There, I was pulled out of my normal environment and knowledge base. I was on a different continent in a church, and I—a biochemist—was using a mainframe computer for long biophysical calculations. It was an amazing experience."

As the new senior associate dean of research, Mochly-Rosen aims to foster those kinds of translational discoveries: the application of basic research to therapies for patients. She hopes to encourage researchers to look beyond their areas of expertise and to make it easier for them to cross barriers they might encounter along the way.

Her appointment, announced in late November, comes at an important juncture for the medical school, which is making a huge effort to move translational research forward through its four recently established research institutes, the new comprehensive cancer center and other initiatives.

"Translational research is about reducing barriers between cultures and facilitating the use of a common language," Mochly-Rosen said. "It's a matter of teaching each other enough so that together we can do something more than each of us can do."

Mochly-Rosen will share the new deanship responsibilities—and an office—with Harry Greenberg, MD, the Joseph D. Grant Professor of Medicine. She replaces John Boothroyd, PhD, professor of microbiology and immunology, who stepped down from the post in September after three years.

To manage her new responsibilities, she gave up her post as chair of the Department of Molecular Pharmacology; the new chair is James Ferrell, MD, PhD, professor of molecular pharmacology and biochemistry.

"I am particularly pleased that Dr. Daria Mochly-Rosen has agreed to take on the responsibilities of senior associate dean for research," said Philip Pizzo, MD, dean of the School of Medicine. "She is an internationally recognized basic scientist whose work has provided fundamental insights in its own right. In addition she has observed how some of her research might impact human disease and has sought ways to create connections from her research laboratory to the patient."

First and foremost, Mochly-Rosen wants to strengthen basic research—the search for basic understanding of fundamental questions that may not yield an immediate application. "It's very important for us to encourage, celebrate and facilitate basic research for its own sake," she said. "Otherwise there is nothing to translate."

Mochly-Rosen trained as a basic researcher, receiving her degree in chemical immunology at the Weizmann Institute of Science in Israel, her native country. She came to UC-Berkeley to do her postdoctoral studies under Daniel E. Koshland, PhD, the former editor of Science magazine and a renowned biochemist, and then moved on to UCSF. She arrived at Stanford in 1993.

Her work focuses on a family of very similar enzymes. In 1988, she found that the enzymes occupy different locations within a cell. That finding suggested that the function of the enzymes was determined by where they sat within the cell. To prove that, she turned to heart cells, as she could easily measure the response—the change in heartbeat—when the enzymes shifted locations in response to different stimuli.

And so it was that she became a translational researcher.

Mochly-Rosen began to learn about heart disease and ally herself with cardiologists, inviting a cardiology fellow to work in her lab. After she had identified the key areas in the protein and done more lab work with her colleagues, she moved on to pig studies, which showed that inhibiting one of her prized enzymes, known as delta protein kinase C, or PKC, significantly limited the damage from heart attacks.

Mochly-Rosen then took a year off from Stanford to launch a company, KAI Pharmaceuticals in South San Francisco, that would move the findings into the clinic.

She noted that by continually venturing outside her areas of expertise—talking to physiologists and collaborating with cardiologists—she and her colleagues were able to do the right experiments to convince others and eventually the federal Food and Drug Administration that they had produced a compound that might minimize the damage after a heart attack. But, she said, their goal wasn't to make a drug but to begin to understand why cells have several members of the same family of enzymes, a true basic research question.

"I feel as a basic researcher, I have the best job—being paid to fulfill my curiosity," she said. At the same time, she added, "If my research leads to something useful, it's my obligation to see it through."

She said she does not expect others necessarily to follow her path into the world of start-ups, as there are many routes to discovery and translation. "There should be no formulas, but a menu of opportunities for how to take something forward if it has use," she said.

Mochly-Rosen said she expects to devote at least 20 percent of her time to her dean's job. She'll continue to teach and to do research: "You'll have to kill me before I will give up my lab," she said.