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  F E A T U R E S  
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FEATURES
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GUIDING GROUNDBREAKING WORK

'Matchmaker ' Jan Nolta serves as catalyst for collaborative research

 "" PHOTO — Jan Nolta, one of the nation's leading stem cell experts, and John Laird, an internationally renowned interventional cardiologist, are preparing for the first stem-cell clinical trials at UC Davis using marrow-derived stem cells from patients to repair damage to heart tissue following a heart attack and to restore blood flow in patients suffering from peripheral vascular disease.
 
Jan Nolta, one of the nation's leading stem cell experts, and John Laird, an internationally renowned interventional cardiologist, are preparing for the first stem-cell clinical trials at UC Davis using marrow-derived stem cells from patients to repair damage to heart tissue following a heart attack and to restore blood flow in patients suffering from peripheral vascular disease.
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In three short years, the UC Davis Stem Cell Program has moved to the forefront of regenerative medicine research in California.

The program is near the top of the list of institutions funded by the California Institute for Regenerative Medicine (CIRM), the state stem cell agency. It has grown to include more than 135 basic, translational and clinical faculty members, is involved in innovative partnerships both on and off campus, and is months away from opening a state-of-the art facility that will allow the start of stem cell-based clinical trials.

Director Jan Nolta is the driving force behind the program, but takes only partial credit for these achievements.

"I've really just been playing matchmaker," Nolta says.

Rapid growth

Since her arrival, Nolta has been meeting with researchers throughout campus to learn more about the stem cell research under way, as well as which researchers were poised to add stem cell research to their programs. She identified 15 disease-team areas – from HIV/ AIDS to hearing loss. Five of these teams, Nolta reports, were among 20 academic teams selected by CIRM through competitive review to move forward to full application for funding.

"When I got here, people were already doing great work," Nolta says. "Now, they are doing it together in additional areas."

The research team of Randi Hagerman, a pediatrician who specializes in fragile X syndrome, and her husband, Paul Hagerman, a molecular biologist, discovered the fragile x-associated tremor/ataxia syndrome ( FXTAS, pronounced "FAX-tass") in 2001, in which a small mutation  also called a premutation  occurs in the same gene that causes fragile X syndrome. The genetic mutation is the most common cause of inherited mental impairment and the leading single-gene cause of autism in children. Prior to its discovery, FXTAS was often misdiagnosed as Alzheimer's disease, Parkinson's disease or the more rare Charcot-Marie-Tooth syndrome. In addition to finding treatments that specifically target FXTAS, the Hagermans and their research teams are helping to improve understanding of all age-related neurodegenerative processes.

CIRM grants for UC Davis total over $48 million, with $20 million earmarked for the $62 million Institute for Regenerative Cures, a 90,000-square-foot facility that provides researchers with advanced laboratories, cell manufacturing areas and testing rooms.

The institute's Good Manufacturing Practices (GMP) laboratory – a facility that adheres to strict federal guidelines for the production of cells and other materials used to treat humans – will open later this year. Clinical trials will begin once the validation process is complete and the facility is operational.

"This will be the premier human stem cell GMP facility in Northern California," says Gerhard Bauer, director of the GMP lab.

The first clinical trials at UC Davis will use marrow-derived stem cells from patients to treat vision loss or disruption caused by retinal occlusion (blocked arteries and veins of the eye), to repair damage to heart tissue following a heart attack, and to restore blood flow in patients suffering from peripheral vascular disease.

Partnerships on, off campus

In addition to bringing together individual researchers, Nolta has developed collaborations across disciplines. In May, the UC Davis School of Veterinary Medicine opened its new Regenerative Medicine Laboratory at the William R. Pritchard Veterinary Medical Teaching Hospital. The new lab focuses on use of stem cell therapies to treat injured and diseased horses, but in the future is expected to add treatments for dogs and cats.

PHOTO — Epidemiologist Irva Hertz-Picciotto oversees several federally funded research studies related to autism. They include the Early Autism Risk Longitudinal Investigation (EARLI) study that will follow up to 1,200 pregnant women who already have a child with autism, the Markers of Autism Risk in Babies – Learning Early Signs (MARB LES ) Study and the Childhood Autism Risk from Genetics and the Environment (CH ARGE ) Study. Hertz-Picciotto also is heading up UC Davis’ participation in the National Children’s Study, which is assessing the effects of environmental and genetic factors on 100,000 American children from before birth to age 21. It is the largest study of child and human health ever conducted in the United States.

Nolta says a working partnership with the veterinary school's stem cell program has already resulted in enormous benefits for the School of Medicine.

"We learn a lot about treating human disease from successes in our care of the veterinary patients." Community members have also done a little matchmaking, Nolta says.

PHOTO — Stem Cell Research Program Director
Jan Nolta, immunologist William Murphy and Department of Dermatology Chair and skin cancer expert Fu-Tong Liu, are working together to explore ways to target and kill cancer stem cells, which can remain and metastasize following chemotherapy.  ""

Stem Cell Research Program Director Jan Nolta, immunologist William Murphy and Department of Dermatology Chair and skin cancer expert Fu-Tong Liu, are working together to explore ways to target and kill cancer stem cells, which can remain and metastasize following chemotherapy.
 
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"The patients and patient advocates for Huntington's disease sought me out early on," she recalls. "After meeting them, helping to cure this dreadful disease has become one of my true passions in life."

The outreach proved beneficial. In May, CIRM awarded Dr. Nolta's team a $2.7 million grant to create and test a new treatment for the disease, using mesenchymal stem cells harvested from a normal donor's bone marrow and engineered to fight the mutant protein.

"Families like mine have been waiting for an intervention for Huntington's since the gene was located 16 years ago," says Judy Roberson, president of the Huntington's Disease Society of America's Northern California Chapter. "Now, thanks to CIRM support and the research at UC Davis, there's real hope."

Training others a key

Nolta says she is particularly proud to be able to partner with her former mentors at California State University, Sacramento, to train skilled scientific and laboratory personnel who will fill the demand for jobs in the growing number of stem cell research laboratories. In March, CIRM awarded a three-year, $1.3 million "Bridges to Stem Cell Research" grant to fund a program of internships and related opportunities for cellular and molecular biology students from Sacramento State to work in UC Davis stem cell laboratories.

 "" Disease Team Areas within the UC Davis Stem Cell Program: Peripheral vascular disease, Hearing loss, Bladder disorders, Cartilage and bone injuries and disease such as osteoporosis, Liver disease, Eye degeneration and blindness, Heart disease and stroke, Kidney disease, Neurodegenerative diseases such as Parkinson's, Huntington's, Alzheimer's, ALS, Lung disease, Neurodevelopmental disorders such as autism and fragile
X-related disorders, Burns and non-healing ulcers, Tumor stem cells and cell-based immunotherapy for cancer, Blood disorders, leukemia, sickle cell anemia, Immune system disorders, HIV/AIDS
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"This grant provides our students with a tremendous opportunity for careers in one of the leading areas of scientific research," says Laurel Heffernan, associate dean and professor of biological sciences at Sacramento State. Dr. Heffernan was Dr. Nolta's former mentor at CSUS, and has helped many other students from disadvantaged backgrounds to become academic and community leaders.

The stem cell program is also working with The Jackson Laboratory, a Bar Harbor, Maine, company whose Sacramento facility is developing new therapies for cancer, Alzheimer's, Parkinson's and other diseases. UC Davis researchers are using some of the unique animal models developed by the company in their research. Nolta predicts a mutually beneficial collaboration.

Both Bauer and Nolta say UC Davis is becoming a major leader in the state and the country in stem cell research.

"This is a great collaborative environment with a real focus on innovation," Bauer says.

Nolta agrees. "What I love about UC Davis is the wonderful spirit of teamwork throughout the basic, translational and clinical groups and that we all pull forward together as teams rather than having internal competition. With our great spirit of teamwork and guidance from our community members, we are developing much-needed cures for diseases and injuries that can only be accomplished by groups working effectively together. It truly takes a village."

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  "Every person on our stem cell research teams, from trainee to faculty member, is in this business, and specifically working at UC Davis, to provide the best possible care for our patients  human or veterinary. This goes for basic, translational (bench-to-bedside) and clinical team members. This may seem like a basic tenet of any major academic medical center, but, in many places, science is unfortunately guided by egos and empires. Not so at UC Davis." — Jan Nolta, Director of the UC Davis Stem Cell Research Program  
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