Illinois Medicine

cover story by Richard Asa st in Translation G uy Weinberg, MD, developed a lipid emulsion treatment to resuscitate patients who present with toxicity to local anesthetics and overdoses of a variety of drugs. Mary Jo LaDu, PhD, followed the link between the gene apoE and Alzheimer's disease, and her work has made a major impact on research around the globe. Victor Gordeuk, MD, director of the College of Medicine's Sickle Cell Center, leads a team that has built an airtight feedback loop of basic research and clinical observations. These are just a few examples of how translational research continues to transform the College of Medicine into a home for the integration of basic and clinical research. To bolster its existing talented leadership, the college has strategically recruited five new department heads with experience promoting this tight bench-to-bedside connection and providing mentorship support to NIH-funded researchers (see sidebar profiles, page 24). Their work will help to foster the university's strengths in developing technological innovations for clinical applications and fuel the college's ability to address unmet medical needs. The college also has undertaken a strategy to enhance the research environment and infrastructure for translational science through its partnership with the federally funded Center for Clinical and Translational Science (CCTS). Many of the college's investigators have relied on support services such as study design, regulatory support, biomedical informatics, community engagement and a clinical research facility provided by the CCTS, which serves as home for the concept and a nexus for multidisciplinary collaboration. For example, the center awards pilot and just-in-time grants that provide stimulus to investigators with novel ideas at the forefront of translational science, enabling preliminary research that will help prepare them for externally funded research grant proposals, says CCTS co-director Robin Mermelstein, PhD. Just-in-time grants increase the responsiveness and competitiveness of proposals by, for example, helping investigators bolster preliminary data sections. "We emphasize collaborations among faculty and across departments, certainly throughout the College of Medicine," Mermelstein says. "They bring together different perspectives on approaching a problem, and that creates new linkages, particularly in bringing basic scientists in contact with clinical scientists in a feedback loop, which is critical." Serving a dual role as director of the CCTS and dean of the College of Medicine, Dimitri T. Azar, MD, MBA, has a unique perspective on the integral role of translational science in today's research landscape. "There has always been patient- and community-centered research here, along with a well-established and respected infrastructure in basic research," he says. "We have the opportunity to enhance the impact of our research through collaboration. A structured approach, through translational science, will make the whole greater than the sum of the parts. It will enhance the effectiveness of our institution across the clinical and basic research spectrum. Ultimately, our collaborations will break down the traditional barriers that have developed over the years and will help us solve more health-related problems." UIC is one of 60 institutions funded by the Clinical and Translational Science Awards program, administered by the National Center for Advancing Translational Science, created at the National Institutes of Health in 2012. The purpose of NCATS is to help "enhance the development, testing and implementation of diagnostics and therapeutics across a wide range of human diseases and conditions. By improving the process through which diagnostics and therapeutics are developed, NCATS aims to make translational science more efficient, less expensive and less risky," according to the NCATS website. W hen Weinberg left his position as a basic researcher at the National Institutes of Health nearly 30 years ago, he never expected to be back in the laboratory. Instead, his career has dovetailed anew with the bench at the College of Medicine, jump-started initially by his desire to understand why a patient with carnitine deficiency almost died from a very small dose of local anesthetic. That question led to animal studies of the mitochondrial effects of local anesthetics, which confirmed Weinberg's suspicion that they inhibit normal mitochondrial metabolism of fatty acids. Building on this result, Weinberg and his team did studies in 2000 to replicate the metabolic effects of carnitine deficiency—which led to the unexpected observation that pre-treating an animal with an intravenous lipid emulsion rendered it very resistant to local anesthetic toxicity. The follow-up experiments identified intravenous lipid emulsion infusion as a very effective method for reversing an otherwise fatal local anesthetic overdose and toxicity. "That has now led back to the bedside and has saved lives in operating and emergency rooms across the globe," Weinberg says. illinois medicine | 23

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