University at Buffalo - The State University of New York

Published: March 2, 2006

By JESSICA KELTZ
Reporter Contributor

Matthew Disney began trying to understand the way RNA molecules are structured about 10 years ago while working toward an undergraduate degree at the University of Maryland. But he says he doesn't intend to change his goal—developing better prescription drugs—anytime soon.

The goal of Matthew Disney’s research is to better understand the structure of RNA molecules in order to design more effective prescription drugs.
PHOTO: NANCY J. PARISI

"I'd be disappointed if I didn't work on this for the next 30 years," says Disney, who joined the UB faculty as an assistant professor in the Department of Chemistry, College of Arts and Sciences, this past fall. "This is one of those things you work on for a long time. It could be endless, and endlessly satisfying."

Disney studies RNA and how it folds. Unlike DNA, which forms in the famous "double helix" pattern, RNA doesn't have a single, predictable structure, he explains. RNAs can fold into many different structures, unlike the repeatable patterns that DNA folds into. RNA folds into many different small motifs that often serve as platforms for interacting proteins or other RNAs.

"If you have the sequence, you can predict the structure accurately," Disney says. This structural information is invaluable for understanding how the RNA works and, potentially, how to design drugs that target it.

The goal of Disney's research is to better understand the way RNA molecules fold and design drug-like compounds that bind the RNA in a predictable manner and inhibit its activity. To achieve this goal, we need to find a code for recognition of RNA, he says. Armed with such a code, scientists could create antibiotics that kill drug-resistant strains of bacteria, for example.

"I think we could make a big impact on the way scientists design drugs," he says.

Physicians prescribe drugs knowing what they treat, but usually not their modes of action, Disney notes. Being able to efficiently design drugs that are specific for the target of interest and being able to predict potential off-target effects would be valuable for making specific drugs, he adds.

"You want to be able to design compounds that are better than the ones currently used so you could fight antibiotic resistant bacterial infections."

In addition to potentially fighting antibiotic-resistant bacterial infections, this RNA research also could make strides against cancer and genetic diseases, such as sickle cell anemia and cystic fibrosis, Disney says. This is because RNA plays important roles in a variety of diseases.

He says an RNA inhibitor could be even better than a DNA inhibitor because RNA has a greater range of functions within human cells. Moreover, pharmaceutical compounds that target DNA have to get into a cell's nucleus, the only place DNA is present; this is a challenge for making compounds that target DNA, Disney says.

"Since RNA is present both in the cell's nucleus and cytoplasm, you do not need to get a compound only into the nucleus to target it," he says.

Disney came to UB fresh from a year and a half in Zurich, Switzerland, where he worked as a postdoctoral researcher at the Swiss Federal Institute of Technology (ETH). Prior to that, he worked for six months in the same position at MIT. In Europe, scientific research is conducted differently; he says in many cases, professional technicians do the routine analysis to see if you made the compounds you are interested in.

The technicians, he says, were very skilled and did excellent work, but he prefers doing his work himself.

"That drove me crazy," he says. "You lose some satisfaction in your science because having to rely on someone else to do your analysis puts limits on your work. The only limits I want are what my mind can think and what my hands can do.

"At the same time, living in a foreign country gives you a better understanding of the European perspective and it was interesting to see it firsthand. The war in Iraq made things difficult, but living in a foreign country was overall a great experience and more Americans should travel to other countries and experience their culture. That being said, it is great to be back in the United States," he says. "Moving back here makes me have a greater appreciation for the U.S."

"Before his MIT appointment, Disney, who grew up in Baltimore, earned a B.S. and an M.S. in chemistry from the University of Maryland-College Park and a Ph.D. in biophysical chemistry from the University of Rochester. He last taught while he was in Rochester—his MIT and ETH fellowship being entirely research-oriented—but says that getting back into the swing of teaching was relatively easy.

During the fall semester, Disney taught "Introduction to Medicinal Chemistry," taken by a mix of graduate and undergraduate students. This semester, he's teaching "Chemistry of Biological Systems."

"It was good to be able to interact with the students," he says. "It was challenging trying to get them to communicate with me scientifically, but toward the end of the course, they started to talk more."

Getting his research program established also has gone well.

"People have been very helpful in helping me get started," he says. "I don't think it could have been a better start-up situation in terms of support from the faculty and staff."

He received a five-year, $50,000 new faculty award from the Camille and Henry Dreyfus Foundation, and his work also is funded by the New York State Center of Excellence in Bioinformatics and Life Sciences.

Disney lives in Williamsville with his wife, Jessica Childs-Disney, a UB adjunct professor of chemistry who will join the faculty at Canisius College in the fall as an assistant professor of biochemistry.