2008 CSL Undergraduate Summer Research Stipends

Angela Pak

Fourth-year undergraduate, Molecular Biochemistry and Biophysics

Nick Menhart

Associate Professor of Biology

Determining the role and clinical relevance of exon skipped motifs of the dystrophin rod

Angela's work may improve gene therapy for Duchenne muscular dystrophy.

For two years — funded by the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases — Menhart and his team have been mapping the rod region of dystrophin, the protein whose defect underlies Duchenne muscular dystrophy, a fatal disease that strikes 1 in 3,500 boys. Their work is critical to gene therapy for DMD.

Dystrophin is very large, in part why this disease is so common. It is coded for in its gene in a modular fashion in 79 distinct pieces called exons. A defect in just one or a small number of exons disrupts all protein production. Like a train derailment on a subway line, if one piece of track is broken, it can bring the whole system to a halt as trains stack up.

Researchers are trying a strategy called exon-skipping to restart protein production, "detouring" around individual patients' exon defects. But detouring can cause problems. Skipping can affect the nature of the dystrophin made and whether it will be effective.

"That's where we come in," says Menhart "We're trying to determine the properties of the protein so that we can plan effective detours." It is critical to know as much as possible about dystrophin and how edited dystrophin works.

"I've known since I was a little kid that I wanted to help people who are sick," says Angela, a student from Guam who plans to study medicine after IIT. This summer, using recombinant DNA technology, she prepared test versions of various alternative repairs involving exon skips and determined which repaired dystrophins most closely mimic the intact natural dystrophin. The goal was to pinpoint the most productive dystrophin repair sites, including repairs being studied for actual patients.

Angela said, "Studying something that is still a mystery to the scientific world — that can possibly make a positive impact in our society — is so exciting."

Photographer: Mindy Sherman, IIT Communications & Marketing

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2008 CSL Undergraduate Summer Research Stipends

Angela Pak

Nick Menhart

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