UCSF names first director of its stem cell biology program

By Jennifer O'Brien

Signaling an important milestone in its pioneering stem cell efforts, UCSF School of Medicine has announced the first director of its Developmental and Stem Cell Biology Program. Arnold R. Kriegstein, MD, PhD, scientific director of the Neural Stem Cell Center at Columbia University, will assume leadership in August.

“Kriegstein brings to UCSF an international reputation for his work on neuronal stem cells in the developing brain, and is ideally suited to lead this important UCSF program at the scientific frontier,” said UCSF School of Medicine Dean David Kessler, MD, in his recent announcement.

The program will be an important new cornerstone of the UCSF Parnassus Campus, says Kessler, the site of many discoveries in the biomedical sciences, including two that led to Nobel prizes—one regarding the genetic underpinnings of cancer, and one regarding the identification of prions, which cause some forms of neurodegeneration, including “mad cow” disease. The Parnassus Campus is also where Gail Martin, PhD, UCSF professor of anatomy, was one of the first scientists in the world to isolate precursor cells from mouse embryos and coined the term embryonic stem cells, laying the groundwork for current worldwide research on the use of human embryonic stem cells to treat disease.

“We are extremely pleased to welcome Dr. Kriegstein to UCSF,” says UCSF Chancellor J. Michael Bishop, MD. “The field of stem cell research is in its infancy, but the potential to add to our basic knowledge of human development and to establish therapeutic applications is enormous. UCSF has been a pioneer in the field from the outset, and we look forward to Dr. Kriegstein’s leadership as our scientists continue to explore the nature and capacity of these cells.”

The UCSF Developmental and Stem Cell Biology Program, established in August 2002 and led by an interim faculty committee during the Director search, was one of the first such programs to be created in the country. Launched with a $5 million matching grant from Andy Grove, the chairman of Intel Corp., it funds basic studies in stem cell biology and their translation into clinical practice. The goal of these studies, involving both animal and human cells, is to pave the way for treatments for such diseases as diabetes, cardiovascular disease, Parkinson’s disease, Alzheimer’s disease and spinal cord injury.

“I am honored and extremely excited to be taking the helm of the UCSF Developmental and Stem Cell Biology Program,” says Kriegstein. “UCSF researchers have been pioneers in the stem cell field, demonstrating great creativity and ingenuity in their research, as seen in numerous important advances, as well as a determination to persevere.”

UCSF researchers Susan Fisher, PhD, UCSF professor of stomatology, anatomy and pharmaceutical chemistry, and Meri Firpo, PhD, UCSF assistant research geneticist in the Deparment of Obstetrics, Gynecology and Reproductive Sciences, currently are working to derive human embryonic stem cell lines using new techniques that would make them eligible under Food and Drug Administration standards for transplantation into people. They each are doing so with funding from various sources, including the private sector (Geron Corp. or foundations), a University of California Discovery grant and/or gifts to the UCSF Developmental and Stem Cell Biology Program.

Stem cell researcher Renee Reijo Pera, PhD, UCSF associate professor of obstetrics, gynecology and reproductive sciences, and Fisher, will co-direct a new Human Embryonic Stem Cell Center, under the umbrella of the overall Program.

Earlier, UCSF was one of only two universities in the United States that derived human embryonic stem cell lines that qualified for inclusion on the National Institutes of Health Stem Cell Registry, established in 2001. These cell lines, derived with funding from Geron Corp. and a UC Discovery grant, currently are being distributed to scientists around the world for study, with funding support from the NIH. While the National Institutes of Health funds studies on human embryonic stem cell lines included on the NIH Stem Cell Registry, it does not fund studies aimed at deriving new stem cell lines or studying these lines.

The new Developmental and Stem Cell Biology Program, which this past winter met the Grove “Stem Cell Challenge”—raising the funding level to date to more than $11 million in gifts and matching funds—recently awarded $50,000 grants, with the potential for renewal, to four scientists. The grants fuel studies aimed at:

*Developing a gene-trapping technology to examine the decision-making process that prompts embryonic stem cells to develop into specialized cells. The tool, being developed by Bruce Conklin, MD, UCSF associate professor of medicine, and Whittmore Tingley MD, PhD, assistant professor of medicine, both of the J. David Gladstone Institute of Cardiovascular Disease, is currently focused on the genes of insulin-producing cells of the pancreas, with the goal of developing strategies for treating diabetes. The tool also could be applied to studies of many diseases and conditions, including heart failure, liver failure, Alzheimer’s disease, Parkinson’s disease and stroke.

*Identifying the genes involved in maintaining adult neural stem cells in mice, with the intent of “knocking out” these genes in order to discover the precise function of the cells. The goal of the work, being conducted by Y.N. Jan, PhD, UCSF professor of physiology and biochemistry and biophysics, is to determine the function of adult neural stem cells in humans, in order to develop strategies to treat brain disorders such as Parkinson’s disease.

*Studying the genes involved in the development of human sperm and egg cells, as well as embryonic stem cells, with the goal of better understanding the process of human development and the problems that can occur, including infertility and birth defects, with an eye toward treatment. The work is being conducted by Renee Reijo Pera, PhD, UCSF associate professor of obstetrics, gynecology and reproductive sciences.

*Investigating the role of stem cells in the regenerative process that takes place in planarians, or flat worms, which are able to regenerate severed tissue within a few days. The study, led by Ron Vale, PhD, UCSF professor and chairman of the Department of Cellular and Molecular Pharmacology, is aimed at understanding the regenerative potential of planarians, which may enable researchers to identify therapeutic strategies for regeneration of human organs.

Other key areas of stem cell research at UCSF include work by Arturo Alvarez-Buylla, PhD, UCSF professor of neurological surgery, who recently reported the discovery of a ribbon of stem cells in the human brain that potentially could be used to develop strategies for regenerating damaged brain tissue - and that could offer new insight into the most common type of brain tumor; and by Didier Stainier, PhD, UCSF professor of biochemistry, who is pioneering studies of embryonic stem cells in zebrafish, identifying genes that contribute to the development of heart stem cells.

Kriegstein has focused his research primarily on the process by which neurons are born and migrate to the cortex, an issue of fundamental importance to a wide range of neurodevelopmental disorders, including schizophrenia, epilepsy, and learning disabilities.

His team investigates intercellular signaling and proliferation in the embryonic cerebral cortex during fetal stages of development. The findings from the lab have revealed that embryonic neuronal progenitor cells appear to be highly interactive, communicating with each other directly through gap junction channels and responding to their local environment through specific neurotransmitter receptors. In addition, the findings have demonstrated that radial glial cells, long thought to simply guide postmitotic neurons during migration, are neuronal stem cells in the developing brain. The team found that radial glial cells divide to produce neurons that then climb along their parent radial glial cell fiber to reach the developing cerebral cortex. The finding suggests that a radial glial ‘mother’ cell generates and guides daughter neurons, and that in the mature brain a “family” of related, potentially interconnected neurons may form functional units. The identification of the radial glial cell as a key neuronal stem cell in the developing brain has helped shift attention to the role of glial cells as neuronal stem cells in the adult brain, and has the potential to lead to innovative therapies aimed at neuronal regeneration.

Born in Germany, Kriegstein received his MD and PhD degrees from New York University in 1977, and he has held academic appointments at New York University, Harvard University, Stanford University, Yale University, and Columbia University.