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In his laboratory at the University of Texas Southwestern Medical Center at Dallas, David Garbers studied one of life's most basic processes—the way sperm and egg join to create new life. By exploring the molecular mechanics of fertilization and the properties of germ cells—eggs and sperm—Garbers hoped that his discoveries would lead to advances in reproductive biology, including the development of new contraceptives and ways to increase fertility.
"I am fascinated by germ cells and their potential applications to medicine and biology," Garbers said. "The idea of understanding these cells and intervening for the purpose of developing contraceptives, increasing fertility in animals used as food sources, producing new animal genetic models, and possibly helping preserve endangered species are all exciting prospects to me."
Garbers's interest in science was sparked during childhood, growing up on a dairy farm in La Crosse, Wisconsin, where he took advantage of limitless opportunities to explore the natural world around him. Later, as a student at the University of Wisconsin–Madison, Garbers worked nearly full-time to pay his tuition. As part of a work-study program, he pursued research in the laboratory of Neal First, a well-known reproductive biologist who became one of Garbers's mentors. "By the time I finished my degree, I had no doubts that I wanted to pursue scientific research as my major endeavor in life," he recalled. For his Ph.D., Garbers joined the laboratory of Henry Lardy, author of seminal papers on sperm metabolism, pushing him further along a career path in the reproductive biology sciences.
Early in his career at Vanderbilt University School of Medicine, Garbers discovered on the sperm cells of sea urchins a novel family of receptors called guanylyl cyclases, which detect signals from the egg, enabling sperm to know in which direction to swim. He and his colleagues later found the same receptors in higher animals, including mammals, where they are also known to be involved in regulating blood pressure, vision, and intestinal secretions.
More recently, Garbers identified many proteins expressed exclusively on sperm, including an ion channel called CatSper that gives sperm the wiggle necessary to propel them full throttle through the egg membrane. When he disabled the gene for CatSper in mice, sperm were incapable of penetrating the egg. In a separate study, Garbers disrupted a gene called NHE in mice, resulting in sperm that could not even produce the movements needed to swim. The proteins made from the two mouse genes may be viable candidates for a form of male birth control. Both genes have counterparts in humans and appear to be active only in sperm cells. If drugs could be developed to block the proteins made by these genes, these drugs are likely to have fewer side effects than the hormone-based contraceptives currently on the market.
Garbers was also developing technology to maintain and grow male germ cells in the laboratory, with the goal of manipulating the genomes of these cells. Success in this area could lead to a treatment for male infertility, as well as the ability to increase fertility rates, new methods to select against germ cells that carry defective genes, and other advances in reproductive biology. He and his colleagues recently modified the genome of male germ stem cells in rats and bred rat pups that contain the modified genomes. This technology could also lead to ways to target genes for mutations in species other than mice, with the goal of creating animal models for studying both diseases and the genetic defects that underlie them.
Dr. Garbers was also Professor of Pharmacology and Director of the Cecil H. and Ida Green Center for Reproductive Biology Sciences at the University of Texas Southwestern Medical Center at Dallas.
RESEARCH ABSTRACT SUMMARY:
David Garbers targeted the germline for study. His questions were focused on the molecular basis of fertilization and the development of technology to maintain and manipulate male germ cells in culture. He also studied the mechanisms of regulation of the guanylyl cyclase receptor family.
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Photo: Dave Gresham, UT Southwestern News & Publications
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