Left to right, beginning with top row: Daniel Haber, M.D., Ph.D., Friedhelm Hildebrandt, M.D., Beth Levine, M.D., Christopher V. Plowe, M.D., Kerry J. Ressler, M.D., Ph.D., Andrey Shaw, M.D.

Engle is now using her findings to develop mutant mice that may help reveal the details of such breakdowns. "My colleagues and I are excited by the light these studies may shed on the normal development and targeting of cranial motor neurons," she says, "and on why these neurons seem particularly vulnerable to specific gene mutations."

Vulnerable neurons, particularly in very young patients, are also on the mind of another new HHMI investigator, David H. Rowitch of the University of California, San Francisco (UCSF). Rowitch, who treats premature infants at UCSF, rattles off stats he calls "completely unacceptable": nearly 800,000 people in the United States have cerebral palsy, a neurological condition that causes permanent loss of muscle coordination beginning early in life. Health care for patients with the disorder—a potential consequence of premature birth—costs nearly $35 billion a year.

"We actually have a higher incidence of cerebral palsy now than in the 1960s, but this disease has fallen off the radar screen," he says. According to Rowitch, rates are up because more extremely low birth-weight babies, born as early as 6 months gestation, are surviving.

Rowitch, whose laboratory in the UCSF Institute for Regeneration Medicine investigates the biology of the brain's stem cells, is in a position to reduce those numbers. In order to change the standard of care for protecting newborns at high risk for cerebral palsy, he is exploring the basic biology behind the disease, of which little is known.

"Recent studies reveal that up to 50 percent of babies born between 24 and 26 weeks' gestation (about 6 to 6 1/2 months into a pregnancy) will have some degree of cognitive impairment because this is a very important period of brain development," says Rowitch. "While the field of neonatology has made real advances in treatments supporting heart and lung function, when it comes to the brain, we have no therapy to improve outcomes in babies born at these early stages."

Cerebral palsy is usually attributed to an early episode of brain damage, but evidence from Rowitch's lab suggests that the problem is more likely inhibition of the mechanisms the brain normally uses to repair itself.

As he learns more about what goes wrong during brain development to cause the disorder, Rowitch will help establish a program at UCSF whereby new discoveries about the developing brain and nervous system can be applied to tiny patients. "You really need to have a specialized clinical setting that doesn't yet exist for neonates—we'll be the first in the nation. The hope," he says, "is to do for the brain what we're already doing for the heart and lungs."

Photos: Haber: Darren McCollester / PR Newswire ©HHMI, Hildebrandt: Don Alley / PR Newswire ©HHMI, Levine: Tim Sharp / PR Newswire ©HHMI, Plowe: Kaye Evans-Lutterodt / PR Newswire ©HHMI, Ressler: Parker Smith / PR Newswire ©HHMI, Shaw: Sarah Conrad / PR Newswire ©HHMI

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