Three scientists from the University of North Carolina at Chapel Hill School of Medicine and the UNC Lineberger Comprehensive Cancer Center have received prestigious awards from the National Institutes of Health (NIH) aimed at encouraging "high risk" and innovative research.
Klaus Hahn, Ph.D., and Mark Zylka, Ph.D., have received "Transformative" RO1 awards, while Joseph DeSimone, Ph.D., who is also in the UNC College of Arts and Sciences, has been granted a Pioneer Award.
The "Transformative" RO1 awards, new to the NIH this year, are 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.
The new award program was specifically created under the NIH Roadmap for Medical Research to support exceptionally innovative, high risk, original and/or unconventional research projects that have the potential to create or overturn fundamental paradigms. These projects tend to be inherently risky, but if successful can profoundly impact a broad area of biomedical research.
Hahn, who is the Thurman Professor of Pharmacology in the School of Medicine and a member of UNC Lineberger Comprehensive Cancer Center, is collaborating with Harvard University's Gaudenz Danuser, PhD, to develop new methods of measuring how information flows through large signaling networks within cells.
"Our goal is to build on our laboratory's expertise in biosensor design and live cell imaging, combined with Dr. Danuser's expertise in image analysis of dynamic cellular processes, to design completely new ways to observe the complex signaling process that take place both within living cells and within larger networks of cells," said Hahn.
According to Hahn, current methods for measuring and imaging cellular signaling are limited both in terms of the size of the network and the magnitude of changes that scientists can observe at one time. Subtle and rapid changes critical to cell behavior cannot be observed using current laboratory methods and complex cellular networks are beyond the reach of current imaging approaches, so they don't do a good job of imitating what happens in the human body.
Cellular signaling lies at the heart of nearly all cell behaviors, so a better understanding of the subtleties of signaling can generate new insights regarding basic biological processes such as metabolism and aging as well as diseases ranging from cancer to neurological disorders.
Hahn and his colleagues are developing new nanotechnology-based biosensors that work in tandem with the computational approaches developed by the Danuser lab, to enhance sensitivity as neither approach could alone.
Zylka, assistant professor of cell and molecular physiology in the School of Medicine and a member of the UNC Neuroscience Center, notes that more Americans suffer from chronic pain than heart disease, diabetes and cancer combined. Unfortunately, existing pain relievers are not completely effective for all pain conditions and have serious side effects. These facts highlight what is undoubtedly a critical challenge for modern biomedical research: the need to provide pain relief without serious side effects.
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.
In collaboration with Dr. Stephen V. Frye's group in the Center for Integrative Chemical Biology and Drug Discovery at the Eshelman School of Pharmacy, he will use medicinal chemistry to synthesize "prodrugs," pharmacologically inactive compounds that convert to the active form of the drug within the body, in this case for pain relief.
"These studies will allow us to harness a class of enzymes that are found on the membrane of pain-sensing neurons as treatments for acute and chronic pain," Zylka said. "In addition, they have the potential to transform how we treat pain in millions of patients and with fewer side effects."