Friday, October 27, 2006

UCSF Plays Significant Role in Stem Cell Research

By Jennifer O’Brien

It has been a robust year for stem cell research at UCSF. Previously made up of numerous pioneering labs working relatively independently, the research program here has coalesced into one of the premier stem cell institutes in the United States.

Scientists in some 60 labs representing the fields of molecular biology, developmental and cell biology, neurobiology, immunology, and cancer research are bringing their expertise to bear on studies of cell differentiation, or specialization, and tissue regeneration - all studies aimed at illuminating and treating disease.

The researchers are carrying out their studies in adult and embryonic stem cells - as well as similar early-stage cells - of fruit flies, zebrafish, worms, mice and humans. They are working to characterize the nature of the cells and to identify the genes that are expressed as the cells move increasingly toward becoming particular cell types, such as those of the heart, brain or pancreas. They are also exploring the use of stem cells to treat animals with experimental diseases.

Rik Derynck, co-director of the UCSF Institute for Regeneration Medicine, takes a break with colleague Lisa Choy at his lab at the Parnassus campus. Photo/Lisa Cisneros

They are making headway. The scientists, based in labs throughout the University, are gaining insights into the earliest stages of development and the genetic missteps that lead to such conditions as birth defects, infertility, the development of some cancers and the onset of a host of diseases, including breast cancer and Parkinson’s disease.

They also are making advances that could someday lead to the use of stem cells and other early-stage cells as the basis for therapies to treat or replace damaged tissues in diseases such as heart disease, diabetes, Parkinson’s disease, childhood epilepsy, Huntington’s disease, amyotrophic lateral sclerosis (ALS), musculoskeletal diseases and spinal cord injury.

Laying the Foundation

“It is an extraordinarily exciting time in the development of the stem cell field and UCSF’s role in it,” says Arnold Kriegstein, director of the UCSF Institute for Regeneration Medicine. “UCSF, with the breadth and depth of its research enterprise, is in a position to play a significant role in laying the foundation for the field and, eventually, to help move discoveries toward clinical trials in patients.”

The range of research underway at UCSF is broad:

• Arturo Alvarez-Buylla, professor of neurological surgery, discovered a population of neural stem cells in the brain, and is carrying out a range of studies on these cells. One line of his research suggests that adult neural stem cells may be the cause of malignant gliomas, the most common form of brain tumor. If this hypothesis proves true, scientists may be able to target and destroy such rogue stem cells.
• Yerem Yeghiazarians, assistant professor of medicine, interventional cardiology, and director of the Translational Cardiac Stem Cell Program, is exploring the potential of treating cardiomyopathy, a condition that results in weakening of the heart muscle and its pumping ability, with stem cells.
• Mike German, professor of medicine, and Matthias Hebrok, associate professor of medicine, are studying the genes that prompt stem cells to become insulin-producing pancreatic beta cells. Their goal is to create pancreatic islet cells that could be transplanted into diabetic patients to treat their disease.
• Susan Fisher, co-director of the UCSF Human Embryonic Stem Cell Research Center, is working to grow human embryonic stem cell lines in “feeder-free” conditions - i.e., without exposure to mouse or human cells that traditionally have been used to nourish the cells in culture. The goal is to create conditions for the cells that would qualify them under the Food and Drug Administration’s biological safety standards for transplantation, with an eye toward cell-based therapies.
• Renee Reijo Pera, co-director of the UCSF Human Embryonic Stem Cell Research Center, is studying human embryonic stem cells with the goal of identifying genetic mutations that could play a role in some cases of birth defects, infertility and cancer. She also is carrying out studies of somatic cell nuclear transfer, or therapeutic cloning, with the ultimate goal of providing a strategy for creating patient-specific cell lines to study and treat diseases.

Fostering Collaboration

To harness the potential of the research underway, the institute has been organized in recent months along a series of research “pipelines” designed to advance the process by which a discovery moves from the lab bench to clinical trials.

Scientists working at different stages of research in a common organ system or disease area, such as one designated diabetes/pancreas/liver, are now formally linked in a system that promotes collaboration and communication. At the same time, scientists studying the same biological phenomenon, such as stem cell differentiation, but within different pipelines, are now united under “pillars.”

“This organizational structure will foster collaboration and synergy toward a common goal beyond what is already provided by the highly interactive environment at UCSF,” says Rik Derynck, co-director of the UCSF Institute for Regeneration Medicine.

Meanwhile, the institute’s physical space is evolving. This fall, the UCSF Human Embryonic Stem Cell Research Center, constructed with nonfederal funds, will open. It is intended to provide space for research that, under federal rules, cannot be conducted in lab space supported with federal funds. The center will enable scientists to begin new studies and to move existing studies currently conducted off campus into the facility.

And in May of this year, UCSF announced a proposed plan to construct a building on the Parnassus campus dedicated to stem cell research. Ray and Dagmar Dolby have contributed $16 million toward its construction.

The building is designed to bring under one roof 18 labs involved in various areas of human and animal embryonic and adult stem cell and related early-cell studies. It will serve as the core of a research program that will continue to extend throughout UCSF.

“The objective of the building,” says Derynck, “is to foster intensive collaboration and a cross-pollination of ideas across a broad spectrum of labs and disciplines, with the goal of answering fundamental questions about the earliest steps of embryo and cell development.”

Gaining Support

Stem cell research at UCSF is supported with funds from the federal government, foundations and private donors. While this funding will remain critical, says Kriegstein, UCSF and other research universities in California also anticipate support from the California Institute for Regenerative Medicine (CIRM). CIRM, established by California voters with the passage of Proposition 71 in November 2004, is designed to distribute $3 billion for research over 10 years.

It likely will be another year before the lawsuits challenging the constitutionality of CIRM are resolved, but grant money has begun moving from CIRM, thanks to private donors and a loan by the state authorized by California Governor Arnold Schwarzenegger.

As a result, in April, UCSF - along with 15 other California nonprofit institutions - received the first round of funding from CIRM. The funds will be used by UCSF for a three-year training program designed to prepare the next generation of stem cell scientists. UCSF’s training program, led by Reijo Pera and Kevin Shannon, UCSF professor of pediatrics, will provide instruction for 16 predoctoral, postdoctoral and clinical fellows in stem cell research.

And in August, CIRM announced plans to award funding for two research grant programs, both intended to advance human embryonic stem cell research in California.

“The announcement of these new human embryonic stem cell grant opportunities is generating great interest among UCSF scientists who currently are not even working with human cells,” says Kriegstein. “This is a wonderful sign that the field is continuing to move forward with great energy and talent.”