Marc Johnson began his research career studying a rabies-like virus in fish. “Working with fish viruses is really cool research,” he notes, but there are just not a lot of people doing it,” and that sense of isolation was eventually too much. In search of collaboration and community, Johnson switched from fish viruses to HIV. Since then, the assistant professor in MU’s Department of Microbiology and Immunology has dedicated his research efforts to the study of these related humans viruses. He and his collaborators have made great progress in understanding how the HIV virus works in order to develop new therapeutics to combat the disease.
Spinal Muscular Atrophy (SMA) is the leading genetic cause of infantile death and the leading genetic killer of children under the age of two. As an associate professor in MU’s Department of Veterinary Pathobiology, Christian Lorson has dedicated his life’s research to the study of this devastating disease in hopes of someday developing therapies to replace the diseased gene with a ‘healthy” one.
Johnson’s lab research is largely concentrated on the study of the HIV retrovirus. He says his work can be used on three levels. First, he hopes that by learning how the HIV virus works, he will be able to develop new drugs to treat and cure the disease. Second, he hopes that a thorough understanding of the virus will lead to the development of further gene therapy. Third, he hopes that an understanding of virus structure in general will lead to a better understanding of how human cells work. “Just about everything we know about modern molecular biology came from studying viruses,” Johnson says.
Lorson and his lab team are looking at SMA from two distinct yet related directions. First, they are trying to determine what causes SMA, and second, they want to develop gene therapy programs to replace the SMA-causing gene. This research is done in collaboration with several drug and biotech companies.
With research under his belt, Lorson hopes that his team can start to establish clinical trials to test the therapeutic programs they have developed. “The next step is to launch it into animal models and prove efficacy, showing that you can turn around the SMA phenotype [gene expression].”
As a graduate student in the Department of Molecular Microbiology and Immunology in MU’s School of Medicine, Brian Bostick works with professor Dongsheng Duan in the area of gene therapy. Bostick’s research seeks to develop a treatment for the most common form of muscular dystrophy, Duchenne muscular dystrophy, in which patients are missing a gene called dystrophin. Gene therapy involves the replacement or addition of a missing gene. Bostick’s research involves inserting this gene into a virus and then injecting it into an animal body. “Just by using the normal properties of how a virus works,” Bostick explains, “we can actually replace genes that are missing.”
Bostick’s research focuses specifically on the heart disease associated with Duchenne muscular dystrophy, where a gradual weakening of the muscles occurs—starting with the larger muscles—so that patients have trouble breathing by the time they are teenagers. For a long time, such respiratory problems had been the major cause of death among DMD patients, but doctors are now better able to treat the respiratory disease. Because the heart muscle also needs dystrophin to function properly, heart disease worsens as these patients live longer. Heart disease, in fact, is now a major cause of death among DMD patients, a problem that Bostick and his mentor Duan seek to address by developing a heart disease model in mice.
Bostick offers a quick tour of Duan’s laboratory, illustrating the processes involved in several research projects—from the mouse treadmill to the surgical area and where the mice are kept under observation. Delicately selecting several mice, Bostick shows examples of a normal mouse, one with MD, and another with MD undergoing gene replacement therapy. The difference, in both size and activity, between the untreated mouse and the one given gene therapy is remarkable and promising for future applications of this research.