Leading stem-cell expert to join Stanford Medicine faculty

Maria Grazia Roncarolo, MD, a stem cell and gene therapy expert and former scientific director of the San Raffaele Scientific Institute in Milan, Italy, is joining the Stanford University School of Medicine as a professor of pediatrics.

Roncarolo has been recruited to lead the school’s efforts to translate basic scientific discoveries in the field of regenerative medicine into novel patient therapies, including treatments based on stem cells and gene therapy. “My biggest goal is to build an infrastructure and assemble a team of world-class physician-scientists who can take full advantage of the tremendous discovery and knowledge generated at Stanford in order to transfer those into the clinic,” she said.

Roncarolo begins June 15 as chief of the newly created Division of Pediatric Translational and Regenerative Medicine within the Department of Pediatrics, and as a pediatric immunologist at Lucile Packard Children’s Hospital Stanford. She will also co-direct Stanford’s Institute for Stem Cell Biology and Regenerative Medicine.

“Dr. Roncarolo is a world leader in stem cell and gene therapies,” said Hugh O’Brodovich, MD, professor and chair of pediatrics, and director of the Child Health Research Institute at Stanford. “Under her direction, the San Raffaele Scientific Institute has been seminal in showing that these therapies can actually work. Being able to bring her here to Stanford to translate our discoveries into therapies for patients at one of the best children’s hospitals is a perfect match.” O’Brodovich is also the Adalyn Jay Physician-in-Chief at Lucile Packard Children’s Hospital Stanford.

Stanford's unique advantage

Stanford is the only institution in the world that has the antibodies required to purify human blood-forming stem cells, giving it a unique advantage in the quest to develop stem-cell-based medical treatments. Roncarolo, meanwhile, has brought many basic-science discoveries in this field to patients. She holds eight patents and has six pending for methods used in cell and gene therapies. She has published more than 280 scientific papers and 22 book chapters. Her publications have been cited more than 19,000 times.

“No single person has done as much as she in this field, or as successfully,” said Irving Weissman, MD, professor of pathology and of developmental biology, and director of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine. Roncarolo will join Michael Longaker, MD, professor of surgery, as a co-director of the institute.

“We are very excited that Maria Grazia is joining our faculty,” said Lloyd Minor, MD, dean of the School of Medicine. “She is an outstanding basic scientist and translational researcher, and a highly knowledgeable institutional leader. She will be a tremendous asset to our team.”

Bone marrow transplants have been used since the 1960s to treat cancers and inherited diseases of blood and immune cells. Modern stem-cell and gene-therapy research is making such transplants safer and expanding the range of diseases that can be treated. One important refinement, which Roncarolo will help to develop at Stanford, will be the ability to give patients highly purified preparations consisting of blood-forming stem cells first discovered and isolated by Weissman. She joins Judith Shizuru, MD, associate professor of medicine, who studies bone marrow transplantation in adults, in this effort. Scientists think this approach will eliminate many harmful side effects of older protocols in which patients received mixtures of stem cells that included immune cells capable of reacting against patients’ own tissues.

A pediatric immunologist by training, Roncarolo spent her early career in Lyon, France, at the University Claude Bernard, the pharmaceutical company Schering-Plough and the Hospital E. Herriot, where she focused on inherited metabolic and immune diseases, including severe combined immunodeficiency, better known as “bubble boy disease.”

“As a young doctor, I was really struck by the lack of therapies available to these patients and their families,” she said. “This unmet medical need sparked my interest in the establishment of new treatments using stem cell preparations.”

Immune cell discovery

In Lyon, Roncarolo discovered a new class of T cells. These cells, called T regulatory type-1 cells, help maintain immune-system homeostasis by, among other things, preventing autoimmune diseases and helping the immune system tolerate transplanted cells and organs.

In 1989, Roncarolo moved to the DNAX Research Institute for Molecular and Cellular Biology in Palo Alto, Calif., where she was a key member of the team that carried out the first stem cell transplants given before birth to treat genetic immune diseases. Though the in utero stem-cell transplant cured severe combined immunodeficiency, the procedure could not be generalized to other diseases.

This prompted Roncarolo to turn to gene-therapy approaches, which she pursued at the Telethon Institute for Cell and Gene Therapy at the San Raffaele Scientific Institute after moving there in 1998. She became the institute’s director in 2000.

Unlike a bone marrow transplant, gene therapy does not require a donor. Instead, defective stem cells are removed from the patient, engineered to contain functioning copies of the gene and transplanted back to the patient. Roncarolo led a trial of gene therapy for adenosine deaminase deficiency that was considered the gold standard for gene therapy when results on the first 10 patients were published in 2009.

Today, Roncarolo is excited by the possibility of bringing stem cell and gene therapies to greater patient populations. “At Stanford, there are really fantastic discoveries that can be translated into therapies that make a real difference for people,” she said. “I hope to measure my success at Stanford by the number of diseases we can cure.”