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Researchers of MERIT

By Jackie Powder

Excelling in their fields. Consistently pushing boundaries. Questioning accepted theories and seeking new solutions.

These are some of the characteristics that recently earned three Bloomberg School researchers—Valeria CulottaNicholas Ialongo and Barry Zirkin—prestigious National Institutes of Health MERIT Awards. The MERIT (Method to Extend Research in Time) recognizes established scientists who have a history of excellence and show promise of continued success. It carries up to 10 years of additional grant support and is intended to foster the investigators' creativity and eliminate the burden of applying for a grant renewal every three or four years.

NIH does not accept applications for the awards; recipients are selected based on work completed under a specific NIH grant.

For decades, Barry Zirkin's work has centered on understanding the biochemical and molecular underpinnings of reduced testosterone production. Men's declining ability to produce the hormone over time may lead to increased osteoporosis and deficits in cognition, muscle strength and libido. Zirkin, PhD, professor of Biochemistry and Molecular Biology, was the first to show that lower testosterone levels from aging are not caused by a loss of Leydig cells (which produce testosterone in the testis), but result from changes in the cells that inhibit their ability to function properly.

"He [Zirkin] has almost single-handedly advanced the field of male reproductive aging," says Frank Bellino, PhD, Zirkin's former program officer at the National Institute on Aging.

Zirkin's work on Brown Norway rats suggests that suppression of testosterone production through hormonal contraception may prevent aging of Leydig cells. "The acceptability of male hormonal contraception would be enhanced greatly" if it could serve two purposes: birth control when needed, and later, maintaining higher levels of testosterone, Zirkin says.

"NIH-funded research is the most rigorously peer-reviewed research, and these people have been selected as the best of the best." Dean Michael J. Klag, MD, MPH '87

Culotta's groundbreaking research on the origins of inherited forms of amyotrophic lateral sclerosis (Lou Gehrig's disease) centers on the copper-containing superoxide dismutase (SOD) enzyme. Although SOD is an antioxidant that protects against oxidative stress diseases such as cancer, mutant forms of the same enzyme can cause ALS, a uniformly fatal condition.

"When [SOD] mutates, it changes from a beneficial enzyme to one that's very toxic to motor neurons," says Culotta, the first person to show how copper activates the protective enzyme, SOD.

"That's what we've been studying over the past 12 years—how copper moves around in the cell and gets to the protein, and once it does, how it impacts on the protein and its ability to cause disease," says Culotta, PhD, professor of Environmental Health Sciences.

Culotta received international attention in 1997 for the discovery of a protein "chaperone" responsible for transporting copper within a cell to SOD, raising important questions about copper's role in ALS. Her lab's recent discovery of glutaredoxin, another key protein that can disable SOD, may offer more clues as to how the normally beneficial enzyme mutates into a lethal one.

Nicholas Ialongo and colleagues have been tracking nearly 800 students in the Baltimore City school system for the past 13 years, assessing the effects of universal preventive interventions introduced in first-grade classrooms to reduce the risk of later antisocial behavior and drug use. One intervention provided teachers with classroom management training as well as ways to improve reading and math instruction. The other intervention focused on building strong family/school partnerships.

"He's not just following them [the students], but really building theory itself about how kids develop over time with and without interventions," says Elizabeth Ginexi, PhD, Ialongo's program officer at the National Institute on Drug Abuse.

The long-term study stems from a randomized trial initiated by Sheppard Kellam, professor emeritus and former chair of the Bloomberg School's Department of Mental Health.

Among the project's findings: Children who were assigned to the classroom-based interventions received better conduct reports in middle school than the control group. Although the intervention group showed academic achievement gains through middle school, they began to slide in high school—an indication that "booster" interventions may be beneficial.

Ialongo, PhD, professor of Mental Health, is also looking at family, school, neighborhood and genetic factors that may explain the children's differing responses to the interventions. "Such findings can inform our theories of how children develop and how best to intervene," he says.