La Jolla Institute scientist Hilde Cheroutre earns the 2009 NIH Director's Pioneer Award

Hilde Cheroutre to receive $4.7 million to explore autoimmunity

A scientist at the La Jolla Institute for Allergy & Immunology has received one of the National Institutes of Health (NIH)'s top awards -- the 2009 NIH Director's Pioneer Award. The prestigious prize carries with it funding for total costs of up to $4.7 million over five years, and is designed to support the work of exceptionally creative scientists, whose novel proposals offer the potential to make extraordinary contributions to human health.

Hilde Cheroutre, Ph.D., received the award during the Pioneer Award Symposium today at the NIH headquarters in Bethesda, Maryland. NIH Director Francis S. Collins, M.D., Ph.D., announced the winners. Dr. Cheroutre is one of a select group of 18 scientists nationwide chosen for the 2009 prize from among more than 2,300 applicants. The award will fund her innovative research proposal that, if successful, would create a new way of detecting, treating and possibly preventing autoimmune diseases, with the potential for identifying high risk for autoimmunity in newborns.

In announcing the winners, the NIH said the awards are part of its ongoing efforts to encourage highly creative scientists to explore bold ideas that have the potential to catapult fields forward and speed the translation of research into improved health.

"Leaps in knowledge often result from exceptional minds exploring ideas that were considered risky at their inception, especially in the absence of strong supportive data," said an NIH statement describing the awards. "The changing face of biomedical research calls for support of aggressive risk-taking and innovation that will produce tomorrow's conceptual and technological breakthroughs."

Nilabh Shastri, Ph.D., a prominent scientist and immunology professor at UC Berkeley, who previously worked with Dr. Cheroutre, said her selection "justifies the existence of such awards."

"Dr. Cheroutre possesses a remarkable and rare combination of abilities which have allowed her to make seminal research contributions," said Dr. Shastri, noting that Dr. Cheroutre's previous discoveries have opened up novel avenues of research on the molecular mechanisms of immunological memory, regulatory T cells and autoimmunity. "She not only questions dogmas, but also designs appropriate experiments and has the persistence to carry through until the problems are resolved. She is simply one of the best."

Dr. Cheroutre's proposal focuses on pinpointing specific molecular and genetic events that, she believes, could lay at the basis of susceptibility to autoimmunity. She also will work toward developing innovative treatment, and even more far-reaching approaches, that might prevent autoimmunity in those susceptible individuals. Autoimmunity occurs when the body's white blood cells mistakenly attack normal cells. This leads to a host of disorders such as type 1 diabetes, multiple sclerosis and rheumatoid arthritis. "Normally, the immune system provides us protection against pathogens and the generation of transformed cancer cells," said Dr. Cheroutre. "But in autoimmunity, the immune system does not seem to be able to distinguish bad from good cells. It's like the body gets caught in friendly fire. It can cause incredible self-destruction."

If Dr. Cheroutre's premise is correct -- and she proves that certain cellular defects underlie autoimmunity -- it could allow for early detection of those individuals at high risk. "If true, it would enable us to detect at birth whether an individual is genetically prone to autoimmunity."

The second part of her groundbreaking proposal would then come into play through the development of new therapies that could potentially prevent autoimmunity in those people identified as highly susceptible. Theoretically, similar treatments could also be used for those who have already developed autoimmunity.

"If successful, an individual could be treated very early on - right after birth-- to prevent the disease from occurring or they could be closely observed (medically) and the moment they start to show signs of autoimmunity, treatment could begin," said Dr. Cheroutre. "This would enable treatment before autoimmunity starts up and gets out of hand. It is so important to stop or control these diseases before too much damage has occurred. They are kind of like cancer, in that once it gets too far along, it takes a huge toll."

Dr. Cheroutre's bold proposal is not her first venture into unconventional thinking. In fact, she is a world renowned expert on mucosal immunity, whose findings over the years have frequently bucked conventional wisdom on the immunology of the intestines or broken new ground in immunology in general. Such was her 2007 discovery that retinoic acid, a vitamin A derivative, can play a critical role in controlling inflammation in the body, which is the chief cause of inflammatory bowel disease, rheumatoid arthritis and several other autoimmune diseases. Nature Medicine named it one of the key biomedical research advances of the year. The finding was a departure from current understanding and opened a new frontier in inflammation research.

This, of course, is just the kind of researcher the NIH is looking for with its Pioneer award. The NIH selects the recipients through a special application and evaluation process. Distinguished outside experts identify the most highly competitive applicants. The Advisory Committee to the Director, NIH, performs the second level of review and Dr. Collins makes final decisions based on the outside evaluations and programmatic considerations.

Unlike the predominant form of NIH research grants that require heavy documentation and significant preliminary data, the Pioneer award does not seek pre-existing data from applicants, since they are dealing with novel concepts that have not yet been tested. Instead, the selection committee looks for highly creative proposals put forth by exemplary researchers, along with proof of past innovation and a record of success.

Dr. Cheroutre said her proposal is based on logic, reason and previous information she garnered in her studies of the mucosal immune system. "It really is my knowledge from the mucosal immune system, and the mechanisms by which the body chooses to tolerate or attack certain substances, that I used to reason and make this proposal," she said.

Dr. Cheroutre finds the Pioneer award both exhilarating and challenging. "The NIH is giving recipients the chance to explore our most imaginative concepts. It's a once in a lifetime opportunity. I hope that the opportunity given to me with this award will ultimately lead to innovative and advanced knowledge that can help to prevent autoimmunity from occurring and effectively treat those people who already suffer from autoimmune diseases."