UC Davis researcher focuses on stem cell safety

Paul Knoepfler

The California Institute of Regenerative Medicine (CIRM) recently awarded a grant of more than $2 million over the next five years to UC Davis Health System researcher Paul S. Knoepfler, who is exploring ways to ensure that certain types of stem cells can be safely used in medical treatments.

Knoepfler, an assistant professor of cell biology and human anatomy, received one of the institute's New Faculty awards, which support promising M.D. and Ph.D. scientists in the early stages of their careers as a way to foster the next generation of California stem cell scientists. His research proposal, entitled "Molecular Mechanisms Governing hESC and iPS Cell Self-renewal and Pluripotency," was approved by CIRM's 29-member governing board during a meeting recently on the Stanford University campus.

Knoepfler, who also holds a position at the Institute for Pediatric Regenerative Medicine at Shriner's Hospital for Children Northern California, earned his doctorate in molecular pathology and specializes in stem cell and cancer-related research. Much of his work has focused on deciphering how stem cells are programmed and how that programming can go awry, thereby causing birth defects or cancer.

While there is great potential for using newly identified stem cells to effectively treat disease and injury, a major challenge in regenerative medicine is finding ways to safely use them for human therapies. Adult stem cells, which are undifferentiated cells found throughout the body of both adults and children, have been used for years to successfully treat leukemia and related bone and blood cancers. But two of the most promising stem cells now under investigation, human embryonic stem cells (hESC) and induced pluripotent stem cells (iPS), have been shown to cause tumors in mice. Physicians and scientists, including Knoepfler, recognize that further study is required.

Ann BonhamStem cell research is a top priority for UC Davis, and CIRM's support for both individual investigators and needed facilities greatly complements our goals of advancing science to improve health care for all."
Ann Bonham, executive associate dean for academic affairs.

"We know quite a lot about what makes stem cells attractive as potential tools for regenerative therapies," said Knoepfler, "but, surprisingly, we know almost nothing about the cellular mechanisms that prompt even normal stem cells, cells that have not undergone any mutations, to cause tumors. Since we won't be able to use them in treatments until we can prove their safety, this award from CIRM will be a major catalyst for my work in this crucial area of regenerative medicine."

Knoepfler is focusing on one of key culprits in the tumor-forming capacity of stem cells, a gene called Myc. The gene not only plays a significant role in the positive, normal functions of many stem cells, it is also one of the most potent cancer-causing genes in humans. It recently was found to be a critical factor in driving iPS cells to form tumors.

"Unfortunately, we can't simply delete the Myc gene," noted Knoepfler. "It is important for the efficient generation of iPS cells, and research suggests it may play a key role in their maintenance and function for regenerative medicine."

In order to ensure the safety of stem cells without eliminating their beneficial role, Knoepfler has developed two lines of research: 1) to look at how the Myc gene works in iPS and hESC cells in order to identify the cellular pathways that generate positive effects while eliminating the gene's negative properties; and 2) to identify novel, functionally important stem cell factors that can substitute for Myc or work independently of it.

UC Davis Stem Cell Program

For patients and families suffering from chronic disease or injury, the promise of stem cell therapies offers great hope. UC Davis is a leader in advancing that promising goal. It has brought together physicians, research scientists, biomedical engineers and a range of other experts and collaborative partners to establish the UC Davis Institute for Regenerative Cures: a facility supported by the California Institute for Regenerative Medicine. 

The new $62 million institute will be housed in a 90,000 square-foot facility on the university’s Sacramento campus, where collaborative, team-oriented science will advance breakthrough discoveries and bring stem cell therapies and cures to patients.

Click here to learn more

"One of the most exciting aspects of Paul's work is that he is focusing on the safety of induced pluripotent stem cells," said Jan Nolta, director of the UC Davis stem cell program. "Since iPS cells have many of the same properties as human embryonic stem cells, but can be derived from an individual's own skin cells, they represent great promise for individualized, patient-specific regenerative medicine. We just need to find a way to produce these stem cells without their tumor-causing abilities, which is why this grant is so important and could make such a major difference."

Knoepfler's award from the state's stem cell agency is the ninth for UC Davis since the agency began funding research several years ago. In September, UC Davis officially broke ground on the university's new Institute for Regenerative Cures: a facility supported by the California Institute for Regenerative Cures. This multi-year construction project eventually will be the research home to 50-60 senior faculty investigators and upwards of 200 trainees, graduate students, technicians and other support staff.

"Stem cell research is a top priority for UC Davis, and CIRM's support for both individual investigators and needed facilities greatly complements our goals of advancing science to improve health care for all," said Ann Bonham, executive associate dean for academic affairs. "That commitment to research and discovery is reflected in talented scientists like Paul Knoepfler and Jan Nolta, who joined UC Davis in recognition that this is the place where they can make a difference."

UC Davis is playing a leading role in stem cell research, with more than 125 scientists and physicians currently working on a variety of regenerative medicine investigations at campus locations in both Davis and Sacramento. The university is constructing a 90,000 square-foot facility in Sacramento, where researchers will have access to state-of-the-art laboratories and stem cell manufacturing and testing rooms. That project, along with the newly-funded Translational Human Embryonic Stem Cell Shared Research Facility in Davis, will complement the university's Clinical and Translational Science Center, which is supported by the National Institutes of Health (NIH). In 2005, the NIH awarded $6 million to UC Davis to fund a Center of Excellence in Translational Human Stem Cell Research, one of only two such centers in the nation. For more information, visit https://www.ucdmc.ucdavis.edu/stemcellresearch/.