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UCSF stem cell, cancer scientist honored for pioneering studies

UCSF's Robert Blelloch, MD, PhD, has received the 2011 Outstanding Young Investigator Award from the International Society for Stem Cell Research, for his pioneering research on the role of molecular tools known as microRNAs in embryonic stem cells and cancer.

Blelloch will present his research today, June 15, 2011, at the opening of the ISSCR annual meeting in Toronto (6 p.m. EDT). He will participate in a press briefing at ISSCR tomorrow, June 16 (noon EDT).

MicroRNAs play a subtle, but key, role in regulating the production of proteins, which carry out all cell functions. After a gene's message has been transcripted into messenger RNA, microRNA binds a particular site on the mRNA and ratchets down the amount of protein it produces.

In recent years, research on the role of microRNAs in stem cells and cancer has "exploded," said Blelloch, a member of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at the University of California, San Francisco.

Thanks in part to his team, scientists now know that microRNAs are part of the molecular framework that determines an embryonic stem cell's fate. The cell either will duplicate its genetic material and divide into two identical copies of itself, thus "self renewing," or it will begin to differentiate as a particular type of adult cell, say, a heart muscle cell.

Scientists also know that faulty microRNA function allows unregulated stem cell growth, contributing to cancers. These molecular tools regulate the switch between proliferation and differentiation in both stem cells and cancer.

There are many hundreds of microRNAs, with different roles. Furthermore, each microRNA influences hundreds of messenger RNAs, exerting significant influence on the cell.

During the last few years, Blelloch's team has reported several key findings. In 2008, they reported that microRNAs promote self renewal of embryonic stem cells in mice (Nature Genetics, 2008). In 2009, they showed that when those same microRNAs were inserted into adult cells the cells de-differentiated back into embryonic stem cells (Nature Biotechnology, 2009). In 2010, they inserted a microRNA into embryonic stem cells and promoted differentiation, but determined that the microRNA had to compete with microRNAs that promote embryonic stem cell self-renewal (Nature, 2010). This year, his laboratory has been looking at microRNAs as a potential tool to systematically dissect the molecular pathways that regulate cell fate transitions, including dedifferentiation of adult cells to create induced pluripotent stem cells (Nature Biotechnology, 2011).

"People have come to realize microRNAs are remarkably powerful," said Blelloch, associate professor in the Departments of Urology, Obstetrics, Gynecology and Reproductive Sciences and Pathology and a member of the Helen Diller Family Comprehensive Cancer Center.

Using microRNAs for therapeutic purposes has great potential , he said. "They could be used either to induce adult cells to de-differentiate to embryonic stem cells, which could be expanded, manipulated and returned to a patient, or to promote differentiation of embryonic stem cells to produce tissues that would remain integrated in the body once re-introduced." They also could be used to target cancers, and they attract interest from biotechnology companies.

Because microRNAs are small molecules, he noted, they could be delivered in ways similar to everyday drugs, but would likely have far more direct effects than artificially created small molecules, "as millions and millions of years of evolution have molded them to have specific effects on the cells."

Moreover, because they are transient, he said, they could be introduced, have an impact and then be gone in a couple of days. Like a drug, he said, they would be metabolized and not create a permanent genetic change.

"Robert has made significant insights into the molecular regulation of stem cell self-renewal, differentiation, and dedifferentiation, and is helping lay the groundwork for potential therapeutic strategies," said Arnold Kriegstein, MD, PhD, director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF.

His microRNA research is part of his overall interest in the molecular tools that "lock in" differentiation of adult cells. Tight regulation is important for maintaining organ function and avoiding the possibility of uncontrolled cell growth, the basis of cancer. But learning how to unlock the differentiated state would offer potential paths to regenerative medicine and cancer therapies.

"Along with research on DNA methylation and histone modifications, insights into microRNAs should lead to a deeper understanding of the role of epigenetics in development and disease," he said. "We expect they'll all be tied together."

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.


Contact: Jennifer O'Brien
University of California - San Francisco

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