Two receive awards for research to benefit children

Two University of Wisconsin–Madison researchers have received three-year Hartwell Individual Biomedical Research Awards to support research into fungal disease and therapy for attention deficit hyperactivity disorder (ADHD).

Christina Hull, associate professor of biomolecular chemistry, is funded to explore Cryptococcus, a fungus that causes brain infections in people with immune deficits due to cancer treatment, transplant or AIDS. Hull will focus on the spore — the transmissible phase of the fungus — with the goal of understanding how the spore transforms itself into a yeast cell, which can cause brain swelling, blindness and death.

Using high-speed technology at UW–Madison, Hull will screen for drugs that can either block that transformation or treat the yeast infection without unacceptable side effects. “There are not many antifungal drugs, and some of them are quite toxic, because humans and fungi are close relatives,” she says. “If you could give a nontoxic spore-blocking drug to a transplant patient when they start taking drugs to suppress the immune system, that would stop the disease process even if they inhaled these spores.”

Fungal diseases are a growing problem, Hull says. “Fungal spores are ubiquitous in soil and when we stir it up and inhale them, a whole range of infections can start. But if the inhaled spore cannot grow, it cannot cause disease, so learning to block that process could be key in the prevention of many fatal fungal diseases.” The grant will also fund studies on the role that fungal spores play in allergic asthma.

The second Hartwell Award will support studies led by Luis Populin, an associate professor of neuroscience at UW–Madison, toward developing a system to simplify drug treatment for ADHD, one of the most common childhood diagnoses in the United States. The work grows from Populin’s studies of monkeys, which measured the effects of methylphenidate (Ritalin, a common ADHD drug), on working memory and other aspects of executive functioning.

“We found that the effect varied depending on the dose and the individual, which could explain why these dosing decisions often come down to educated trial and error,” he says.

The new research will focus on 60 children and use a computer game developed by Assistant Professor of Psychology Shawn Green to evaluate the effects of methylphenidate. “The game will measure temporal discounting,” says Professor of Psychology Rick Jenison. “Would you rather receive $10 today, or wait a month and receive $100? To the degree that you are patient and trusting, you might take the $100, but most people, especially those with ADHD, take the bird in hand. Luis’ study showed that methylphenidate made the impulsive monkeys more willing to wait. We will use the game to look for a similar effect in children with ADHD in collaboration with Ryan Herringa, a pediatric psychiatrist and an assistant professor of psychiatry.”

The ultimate goal, Populin says, “is to start devising a mathematical tool that would help a doctor choose the dose that is most beneficial for reducing impulsive behavior without hindering working memory, flexibility and other aspects of executive functioning. We will test temporal discounting with a game that children don’t see as boring, but still evaluates impulsivity so the doctor can make a faster, more accurate dosing decision. Then everybody benefits.”

The primary mission of The Hartwell Foundation (based in Memphis, Tennessee) is to grant awards to individuals for innovative, applied biomedical research to benefit children in the United States. Hull and Populin will each receive $100,000 annually for three years. UW–Madison has also received two Hartwell Fellowships, which provide postdoctoral support for two years at $50,000 direct cost per year.