Two Children's Hospital Boston neuroscientists among 12 receiving the NIH Director's Pioneer Award

Five-year grants to advance research in brain plasticity and brain injury from early-life seizures

September 18, 2007

Two Children's Hospital Boston neuroscientists have been named recipients of the 2007 NIH Director's Pioneer Award which supports biomedical scientists exploring bold new ideas. Takao K. Hensch, PhD, and Frances E. Jensen, MD, both of Children's Department of Neurology and Neurobiology Program, were among just 12 scientists receiving this highly competitive, $2.5 million five-year grant. Their work is expected to yield fresh approaches to preventing and treating developmental disorders of the brain.

A total of 449 scientists applied for the 2007 Pioneer Awards, to be announced on September 19. The program, which complements NIH's traditional grant programs, supports exceptionally creative scientists who take highly innovative, potentially transformative approaches to major challenges in biomedical research. These scientists' risky but potentially high-impact ideas may be too novel, span too diverse a range of disciplines, or be at a stage too early to fare well in the traditional NIH peer-review process.

"Critical periods" that shape the brain
Hensch and Jensen, both professors at Harvard Medical School, are each studying early brain development, but from different perspectives. Hensch's research focuses on how circuits in the brain are shaped by experience during "critical periods" in infancy and early childhood, when the brain is especially adaptable and able to rewire itself, and in manipulating the brain at the molecular level so these periods can be recaptured. Defects in the brain's ability to wire itself during critical periods are thought to underlie developmental disorders such as autism, schizophrenia and ADHD.

Takao K. Hensch, PhDUnder his Pioneer Award, Hensch will examine the role of recently-discovered bits of genetic material, known as non-coding RNAs, in this vital process. Non-coding RNAs can influence brain function on the fly--beyond what's hard-wired in people's DNA--allowing the brain to respond to what's happening in its environment. Although the human genome project is complete, the world of non-coding RNAs is largely unexplored. Recently, Hensch and colleagues discovered that these RNAs' activity can be manipulated to re-activate this period of plasticity in adulthood, and Hensch now hopes to test different manipulations in mouse models.

"Given the potential for non-coding RNAs to orchestrate whole networks of genes within the brain, we hope to uncover new therapeutic approaches to developmental disorders," says Hensch.

Curbing the effects of early-life seizures
Jensen's research focuses on mechanisms of brain injury and epilepsy in the developing brain, with specific emphasis on newborn infants. Her work has yielded new candidate therapies for treatments that are now under development for clinical trials. Jensen is also exploring how seizures early in life alter circuits in the brain, resulting in learning deficits, neuropsychiatric symptoms and autism as childhood unfolds.

Frances E. Jensen, MDJensen will use her Pioneer Award to further examine the molecular brain abnormalities that result from early-life seizures, determine how they may lead to learning and memory problems, and identify potential targets for therapy to reverse or prevent these disabling consequences of epilepsy. In addition, since many people with autism also have epilepsy, her laboratory will investigate whether treatments directed at epilepsy-induced brain changes might improve outcome in autistic syndromes.

"To date, most work in the epilepsy field has centered on the mechanism or prevention of the seizures themselves," notes Jensen, a practicing neurologist at Children's Hospital Boston and Brigham and Women's Hospital. "However, epilepsy can involve far more than the occurrence of seizures, and certain kinds of seizures in the immature brain can disrupt brain networks in ways that lead to cognitive and behavioral impairment, learning disorders or autism. We hope to find ways to limit this disruption after an infant or child has suffered seizures."

Jensen, Hensch and the other 10 Pioneer Award recipients will each receive $2.5 million in direct costs over five years. NIH Director Elias A. Zerhouni, MD, will announce the 2007 award recipients at the start of the NIH Director's Pioneer Award Symposium on Wednesday, Sept. 19. The symposium, free and open to the public, will run from 8:15 a.m. to 5:30 p.m. in the Natcher Conference Center on the NIH campus in Bethesda, MD.

For more information on the Pioneer Award, see: http://nihroadmap.nih.gov/pioneer.

Contact:
James Newton
Children's Hospital Boston
617-919-3110
james.newton@childrens.harvard.edu

NIH News Media Branch
National Institutes of Health
301-496-5787
nihnmb@mail.nih.gov

Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 500 scientists, including eight members of the National Academy of Sciences, 11 members of the Institute of Medicine and 10 members of the Howard Hughes Medical Institute comprise Children's research community. Founded as a 20-bed hospital for children, Children's Hospital Boston today is a 377-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's also is the primary pediatric teaching affiliate of Harvard Medical School. For more information about the hospital and its research visit: www.childrenshospital.org/newsroom.

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