UCSF faculty receive $13.7 million from CIRM for stem cell research

By Jennifer O'Brien

Five UCSF stem cell scientists have received New Faculty grants from the California Institute for Regenerative Medicine, support that will allow them to pursue lines of investigation ultimately aimed at developing treatment strategies for such conditions as cancer, heart disease, tooth regeneration, liver disease and amyotrophic lateral sclerosis.

The UCSF grants, which range from about $2 million to $3 million each, total $13.7 million and are intended to support the scientists in the critical early stages of their careers as independent investigators establishing their own laboratories and research programs. CIRM will provide salary and research support for up to five years, creating a stable environment for the faculty to build innovative and robust stem cell research programs.

“These grants are a tremendous boon to the investigators, but also to the stem cell field overall,” says Arnold Kriegstein, MD, PhD, director of the UCSF Institute for Regeneration Medicine. “They will fuel the research of some of the most creative stem cell scientists in the world, allowing them to pursue the significant scientific challenges they have set for themselves.”

The grants, announced today, are the latest round of research funds awarded by the Independent Citizens Oversight Committee, which oversees CIRM. The ICOC awarded $59 million in New Faculty grants to research universities throughout California.

The UCSF researchers will use the funds to explore fundamental questions about the way in which embryonic stem cells function, how they are regulated and what molecular steps lead them to specialize as specific types of mature cells, such as liver cells. In each case, they plan to use the knowledge they gain to explore cell-replacement therapies or identify potential drugs to treat diseases.

The UCSF faculty recipients, their research areas, and grant amounts are:

* Robert Blelloch, MD, PhD — He will study molecules known as small RNAs, which he hypothesizes play a key role in controlling the expression of embryonic stem cells. Understanding the mechanisms that determine and maintain the potential of stem cells will allow the medical and pharmaceutical community to improve the efficiency with which they can produce embryonic stem cell lines, as well as quality control of the resulting cells, he says. ($3,029,897 grant)
* Ophir Klein, MD, PhD — He will explore the molecular processes that regulate the behavior of dental stem cells in mice, with the goal of promoting tooth regeneration and craniofacial abnormalities in humans. As the signaling pathways are similar to those of the liver and other organs, his work will shed light on regeneration of these organs, as well. His ultimate goal, he says, is to help lay the groundwork for growing human teeth and help advance efforts to regenerate larger organs. ($3,075,251 grant)
* Emmanuelle Passegué, PhD — She will study mouse blood stem cells to investigate how they thrive and, at times, accumulate damage that leads to cancer. Her goal is to identify molecular targets for preventing therapy-related organ damage or secondary cancers. She also will use her mouse model of human leukemia to study what molecular changes lead to cancer stem cell formation and function during disease development. The goal of this work would be to design novel therapies that target cancer stem cells while sparing normal stem cells. ($2,274,368 grant)
* Jeremy Reiter, MD, PhD — He will study the genes that contribute to the development of ALS and other forms of neurodegenerative motor diseases. Using a mouse model he developed, his team will examine the impact of mutant genes associated with the diseases on mouse embryonic stem cells, in order to identify the way in which they actually kill the cells. Diseased motor neurons grown in cell culture dishes could be quickly and efficiently screened with potential drugs to discover agents that slow, halt or reverse the cellular damage, he notes. ($2,259,092 grant)
* Holger Willenbring, MD — He will investigate the genes that establish the function of early-stage liver cells. His goal is to use this knowledge to prompt human embryonic stem cells to specialize as early-stage liver cells in the culture dish. If he succeeds, he’ll transplant the cells into a mouse model of human liver disease. This would be proof of principle for the potential of embryonic stem cells for liver cell therapy, he says. ($3,032,510 grant)

## Additional Details Follow:

Descriptions of each grant award are available at http://www.cirm.ca.gov/RFA/rfa_08-01/default.asp

* Robert Blelloch, MD, PhD, is UCSF assistant professor of urology. “Mechanisms of small RNA regulation in early embryonic development.” (RN2-00906-1)
* Ophir Klein, MD, PhD, is UCSF assistant professor of orofacial sciences, pediatrics, and human genetics. “Laying the groundwork for building a tooth: analysis of dental epithelial stem cells.” (RN2-00933-1)
* Emmanuelle Passegué, PhD, is UCSF assistant professor of medicine. “Mechanisms Underlying the Responses of Normal and Cancer Stem Cells to Environmental and Therapeutic Insults.” (RN2-00934-1)
* Jeremy Reiter, MD, PhD, is UCSF assistant professor of biochemistry and biophysics. “High throughput modeling of human neurodegenerative diseases in embryonic stem cells.” (RN2-00919-1)
* Holger Willenbring, MD, is UCSF assistant professor of surgery. “Molecular dissection of adult liver regeneration to guide the generation of hepatocytes from pluripotent stem cells.” (RN2-00950-1)

## Related Links:

* UCSF Institute for Regeneration Medicine
* California Institute for Regenerative Medicine
* University of California, San Francisco