Trauma and the effects of trauma on the human body continue to be an enormous medical problem, one underscored by the fact that 1.4 million trauma survivors are permanently disabled and 140,000 die each year in the United States alone. Modern medicine has done a remarkable job of increasing survival following severe trauma, resulting in a growing number of people living with major disabilities, thus intensifying the discussion surrounding the role of palliative care in trauma medicine. According to Raphael Lee, M.D. Sc.D., Professor, Department of Surgery, and Director of the Program for Research in Molecular Repair, this problem creates a desperate need for therapeutic strategies to immediately reverse the cellular and molecular alterations following various common forms of trauma. Several years ago, the University of Chicago and Argonne National Lab team created the Program for Research in Cell Healing and Repair, now the Program for Research in Molecular Repair, as a forum for information exchange in this area of research and as a catalyst for program project funding.

“The first attempts to address this idea of molecular restoration, actually undoing the effects of physical trauma, and preventing cell death using biocompatible copolymer surfactants, was here at the University of Chicago,” explains Lee. “In 1992, we reported that it was possible to restore physically disrupted cell membranes using biocompatible surfactants that have been in clinical use in blood banking for decades. This opened a new approach to traumatic injury. Subsequently, several university faculty have extended the understanding of molecular mechanics [Ka Yee Lee, Ph.D., Associate Professor, Chemistry, and Milicent Firestone, Ph.D., Argonne National Laboratory] and cellular responses [Lance Becker, M.D., Professor, Medicine, Terry Vanden Hoek, M.D., Associate Professor, Medicine and Eugene Chang, M.D., Professor, Medicine] and post-trauma membrane repair [Jeremy Marks, M.D., Ph.D., Associate Professor, Pediatrics, David Frim, M.D., Professor, Surgery, and Daniel Curry, M.D., Assistant Professor, Surgery].”

While restoring membrane integrity after injury is critical to any successful trauma therapy, many forms of trauma such as thermal burns, dehydration, and freeze injury are associated with unfolding (i.e. denaturation) of cellular proteins as well. Recently, Lee and his peers demonstrated that it was possible to use similar copolymer surfactants to refold denatured enzymes, phenomena that have been corroborated in collaboration with P. Thiyagarajan, Ph.D., Argonne National Laboratory, and by enzyme kinetic studies with Marvin Makinen, Ph.D., Professor, Biochemistry & Molecular Biology. Ultimately, the goal is to understand what happens to cells during traumatic experiences and then to effectively counteract those effects, restore cellular function before irreversible changes occur, and prevent tissue death. In recent collaborations with Purdue University's veterinary school, ambulation was restored in all injured and paralyzed dogs by intravenous injection of these surfactants within hours after trauma.

The application of these methods in trauma therapy is broad and potentially important. The interest in this technology is rapidly growing partly motivated by need for effective therapy for radiation trauma. In collaboration with Ralph Weichselbaum, M.D., Daniel K. Ludwig Professor and Chair, Radiation & Cellular Oncology, Lee's group demonstrated that it was possible to substantially percent acute cell death after instances of severe radiation exposure with membrane sealing surfactant administered after radiation exposure. These surfactant polymers are known to be effective in preventing tissue death after transient interruptions in blood system circulation that occur in cases of myocardial infarction.

“The polymers buffer free radicals of damaged cells, which may limit DNA and protein damage after stroke or cerebral palsy,” says Marks. “How amazing would it be to be able to erase the effects of such events?”

“Ultimately, the fundamental purpose of the Program is to develop strategies that can be administered on site and time of resuscitation of a major trauma victim, that will substantially improve survival and extent of recovery," says Lee. "Our goal is to help people recover fully from traumatic injury."

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