Three scientists from Keck Medicine of USC have won grants exceeding $4.3 million from the California Institute for Regenerative Medicine (CIRM) for research that includes a temporary liver for patients, novel ways to treat immune disorders and developing new animal models for neurodegenerative diseases.
The grants going to USC Stem Cell principal investigators Paula Cannon, Toshio Miki and Qi-Long Ying are part of the CIRM Tools and Technologies initiative, supporting projects that address the challenges of translating stem cell discoveries into cures. The winners were chosen from among 212 proposals to create, design and test the key technologies needed to usher in the era of regenerative medicine.
Sometimes even the most promising therapy can be derailed by a tiny problem.
“Sometimes even the most promising therapy can be derailed by a tiny problem,” said Jonathan Thomas, chair of CIRM’s governing board. “These awards are designed to help find ways to overcome those problems, to bridge the gaps in our knowledge and to ensure that the best research is able to keep progressing and move out of the lab and into clinical trials in patients.”
Liver support system
Miki’s team at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC plans to develop what he calls an “extracorporeal liver support system” for patients with liver failure.
The ELS will house a collection of human liver cells, produced from stem cells, in a device outside of the patient’s body but connected to the circulation. It will be able to function as a temporary liver: removing toxins, preventing irreversible brain damage, and giving the patient’s own liver a chance to recover and regenerate.
If successful, the device will allow patients to recuperate without undergoing liver transplantation.
The project overseen by Miki, an assistant professor of research in the Department of Biochemistry and Molecular Biology at the Keck School of Medicine of USC, is an international collaboration with Katrin Zeilinger at Berlin’s Charité University and Frank Shubert at Stem Cell Systems GmbH, with additional support from Germany’s Federal Ministry for Education and Research.
Blood-forming stem cells
Cannon plans to improve the precision and safety of “targeted nucleases,” which she describes as “scissors” used to edit specific genes in hematopoietic or blood-forming stem cells. Cannon hopes to develop the next generation of targeted nucleases to treat severe immune deficiencies and blood diseases, such as sickle cell disease.
She and her colleagues have already developed a targeted nuclease that could potentially cure HIV/AIDS by introducing a mutation in a gene called CCR5 that confers natural immunity to HIV. Heading into clinical trials, the approach is inspired by the “Berlin patient,” a man cured of both HIV and leukemia through a bone marrow transplant from a donor with a CCR5 mutation.
Cannon is a principal investigator with USC Stem Cell and associate professor of Molecular Microbiology and Immunology, Pediatrics, and Biochemistry and Molecular Biology at the Keck School.
Sophisticated lab rats
Ying, also at the Broad Center for Regenerative Medicine and Stem Cell Research, plans to use stem cell-based technology to create some of the world’s most sophisticated lab rats for research into new therapies for heart failure, diabetes and neurodegenerative diseases.
Transgenic rats will provide an even more powerful tool than transgenic mice, which have allowed scientists for nearly 25 years to study and model a wide range of diseases that also occur in humans. The rat is widely accepted as more similar to the human in its physiology, which is essential for cardiac, metabolic and neurological studies.
An associate professor of Stem Cell Biology and Regenerative Medicine at the Keck School, Ying is collaborating with USC colleagues Justin Ichida, Bangyan Stiles and Ching-Ling (Ellen) Lien, who is also affiliated with the Saban Research Institute of Children’s Hospital Los Angeles.
“At USC, we are committed to developing the critical tools and technologies for the broader scientific community to translate stem cell discoveries into patient cures,” said Andrew McMahon, director of the Broad Center, and chair of the department and university-wide initiative in stem cell research.
“We are grateful for this ongoing support invested in CIRM by the voters in California,” he added. “Their investment is accelerating the progress of scientists at USC and other world-class universities within the state toward the future of regenerative medicine.”