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Mark Zylka, assistant professor of cell and molecular physiology in the School of Medicine and a member of the UNC Neuroscience Center, has received a prestigious Transformative R01 from the NIH.

The T-RO1, or “Transformative” RO1 program, new this year, is named for the institutes’ standard RO1 grants, but without the traditional budget cap or requirement for preliminary results, and with the flexibility to work in large, complex teams. According to the NIH, this means scientists are free to propose new, bold ideas that may require significant resources to pursue.

Dr. Zylka and his lab will investigate new ways to provide pain relief without serious side effects. More Americans suffer from chronic pain than heart disease, diabetes and cancer combined. Unfortunately, existing analgesics are not completely effective for all pain conditions and have serious side effects. A critical challenge for modern biomedical research is the need to provide pain relief without serious side effects. His research will focus on harnessing particular enzymes found on the membrane of pain-sensing neurons and determining if these enzymes can be used alone or in combination to treat acute and chronic pain. In collaboration with a group headed by Stephen V. Frye, Ph.D., in the center for integrative chemical biology and drug discovery at the Eshelman School of Pharmacy, Zylka will use medicinal chemistry to synthesize “prodrugs,” pharmacologically inactive compounds that convert to the active form of the drug within the body. These studies are important in developing new proteins and small molecules that target ectonucleotidases for the treatment of acute and chronic pain, and have the potential to transform how we treat pain in millions of patients with fewer side effects.

Dr. Zylka will directly address this challenge by harnessing particular enzymes found on the membrane of pain-sensing neurons. He will determine if these enzymes can be used alone or in combination to treat acute and chronic pain. These will involve complex studies with genetically modified mice that are missing these enzymes.

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