March 16, 2007

UCSF human embryonic stem cell research fueled with CIRM funding

Susan Fisher, PhD -----

Eight UCSF faculty members intent on using human embryonic stem cells to explore treatment strategies for a variety of disorders—heart disease, stroke, Parkinson’s disease, multiple sclerosis, epilepsy and blood disorders—were among the 29 scientists awarded major grants today by the California Institute for Regenerative Medicine.

Seven of the UCSF grants were awarded to scientists based at UCSF and one was awarded to a researcher at the UCSF-affiliated J. David Gladstone Institutes.

The comprehensive grants to UCSF faculty, totaling $20.6 million, were chosen from among 70 applications from researchers at 23 non-profit institutions in California. They are to fund four years of research.

The grants are designed to support the work of leading scientists who are already carrying out promising studies with animal or human stem cells but need additional funding to fuel or advance their research into human embryonic stem cells.

“CIRM has done a tremendous job of laying the groundwork for a powerful research enterprise,” says Arnold Kriegstein, MD, PhD, director of the UCSF Institute for Regeneration Medicine. “Scientists need to carry out a broad, intensive investigation of human embryonic stem cells in order to determine their potential for treating and elucidating a host of diseases. These grants, coupled with the previous round of research and training grants, advance this effort.”

In most cases, the comprehensive grants issued to UCSF scientists will support research that builds on promising preliminary studies with animal and adult stem cells. Many will involve testing the use of human embryonic stem cells in animal models of particular diseases, such as heart disease.

One study, drawing together four of UCSF’s leading neuroscientists, involves trying to prompt human embryonic stem cells to specialize as a particular type of nerve cell, known as an inhibitory neuron, that could be used to dampen the electrical activity in the brain circuits of patients with Parkinson’s disease and epilepsy.

Another involves trying to prompt human embryonic stem cells to specialize as a brain cell known as an oligodentrocyte, with the goal of using the cell to regenerate the myelin sheath that is damaged in some strokes and in multiple sclerosis.

Yet another aims to prompt embryonic stem cells to develop into blood stem cells that could one day be used to replenish the blood of patients with leukemia and certain congenital blood disorders. Currently, many patients, particularly people of Hispanic and Asian descent, remain without suitable blood stem cells donors, leaving them with suboptimal options.

Several studies are exploring the potential of human embryonic stem cells to specialize as beating heart cells to repair damaged heart muscle and blood vessels. Much of the new work will focus on identifying the best conditions for culturing human embryonic stem cells and identifying molecular characteristics that make them optimal for repairing heart tissue.

Another study, led by a scientist who has already derived five lines of human embryonic stem cells, involves exploring the best methods for deriving these cells. This step is necessary, she says, because the techniques that are currently used are essentially random.

“Given their potential use in patients, it’s critical that we identify the most effective strategies for prompting embryonic stem cells to generate all the cell types of the body,” says the scientist, Susan Fisher, PhD, professor of cell and tissue biology and acting director of the UCSF Human Embryonic Stem Cell Center.

Yet another grant involves trying to prompt embryonic stem cells to specialize as oocytes, or eggs, with the goal of using the cells to carry out somatic cell nuclear transfer, or therapeutic cloning, studies.

The UCSF faculty recipients based at UCSF:

• Harold Bernstein, MD, PhD, UCSF associate professor of pediatrics, cardiology, UCSF Cardiovascular Research Institute, “Modeling Myocardial Therapy with Human Embryonic Stem Cells” $2,229,140

• Susan Fisher, PhD, UCSF professor of cell and tissue biology and acting director of the UCSF Human Embryonic Stem Cell Center, “Constructing a Fate Map of the Human Embryo” $2,532,388

• Arnold Kriegstein, MD, PhD, UCSF professor of neurology, “Derivation of Inhibitory Nerve Cells from Human Embryonic Stem Cells” $2,507,223

• Andrew Leavitt, MD, UCSF associate professor of laboratory medicine, “Understanding hESC-based Hematopoiesis for Therapeutic Benefit” $2,566,702

• Randall J. Lee, MD, PhD, UCSF associate professor of clinical medicine, “Embryonic Stem Cell-Derived Therapies Targeting Cardiac Ischemic Disease” $2,524,617

• Samuel Pleasure, MD, PhD, UCSF assistant professor of neurology, “Human Stem Cell Derived Oligodendrocytes for Treatment of Stroke and MS” $2,566,701

• Renee Reijo Pera, PhD, UCSF associate professor of obstetrics, gynecology and reproductive sciences, “Human Oocyte Development for Genetic, Pharmacological and Reprogramming Applications” $2,469,104

The UCSF faculty recipient at the UCSF-affiliated J. David Gladstone Institutes:

• Deepak Srivastava, MD, UCSF professor of pediatrics and biochemistry and biophysics, Wilma and Adeline Pirag Distinguished Chair, director, Gladstone Institute of Cardiovascular Disease, “microRNA Regulation of Cardiomyocyte Differentiation from Human Embryonic Stem Cells” $3,164,000

The grants are the second set of research funds awarded by the state stem cell agency. The first awards, known as Scientific Excellence through Exploration and Development (SEED) grants, were issued in February and were designed to spark novel ideas and yield preliminary data that then could be extended to full-scale investigations. Twelve UCSF faculty members - nine at UCSF and three at the Gladstone Institutes—received SEED grants, totaling $7.2 million.

The twelfth UCSF faculty member to receive a SEED grant received the funding approval today: Didier Stainier, PhD, UCSF professor of biochemistry, “Endodermal Differentiation of Human ES cells,” $635,242.

The first round of CIRM funds, for training the next generation of stem cell scientists, was awarded in April 2006. UCSF received one of the largest of the three-year training grants, to support 16 graduate students, postdoctoral fellows and clinical fellows.

For a description of each CIRM Comprehensive grant award:

http://www.cirm.ca.gov/

UCSF is a leading university that advances health worldwide by conducting advanced biomedical research, educating graduate students in the life sciences and health professions, and providing complex patient care.

The UCSF-affiliated J. David Gladstone Institutes is dedicated to the health and welfare of humankind through research into the causes and prevention of some of the world’s most devastating diseases.