Dr. Burgess' laboratory studies developmental processes and their relationship to human genetic disease. Specifically, his group employs a variety of modern molecular biology methods to identify and functionally characterize novel developmental genes involved in organogenesis of the ear and maintenance of stem cell populations.
Hearing loss is one of the most common medical conditions affecting the human population, particularly in older adults. Twenty-eight million Americans, including one in three over the age of 60 and half over the age of 85, have some level of hearing loss. Unlike other vertebrates, mammals are unable to significantly regenerate the sensory neurons (hair cells) required for hearing and balance after losses caused by cell damage or cell death. Dr. Burgess' laboratory studies hair cell regeneration in the zebrafish (Danio rerio), which has a remarkable capacity for regeneration. Studies have shown that, after injury, zebrafish tissues as diverse as the retina, heart, fin, spinal cord, and inner ear are capable of complete recovery. Dr. Burgess uses a combination of genetic and genomic approaches to elucidate the gene network that is activated in the zebrafish inner ear stem cell population - known as "supporting cells" - during regeneration.
Before coming to NHGRI, Dr. Burgess was part of a group at the Massachusetts Institute of Technology that pioneered the use of pseudotyped retroviruses for mutagenesis in zebrafish. This technology provided a major breakthrough in the ability to identify genes that are important in the early development of vertebrates. As opposed to chemical mutagens, the use of retroviruses reduces the time required for gene identification from years to weeks. The ability to expose zebrafish to these retroviruses and then quickly identify relevant mutations allows geneticists to perform large-scale mutagenesis and rapid phenotypic screening in a vertebrate system.
Two major projects are central to this research. One involves the transcriptional profiling of the zebrafish inner ear after sound exposure. Intense and extended sound exposure can damage and kill the hair cells of the inner ear. In this project, zebrafish hair cells are killed after 48 hours of sound exposure and then efficiently regenerate over the course of a week. Dr. Burgess' group has collected tissue from zebrafish inner ears at several intervals following sound exposure, and has then determined which genes exhibit significant increases or decreases in expression. Several phases of regeneration have been identified, and over 1,800 genes have been implicated in regeneration. Using these data as a foundation, Dr. Burgess' laboratory is now using a combination of genetics, embryology, and computational approaches to better define the critical genes involved in the regeneration process.
A second related project involves classical genetic screening for genes involved in ear function and hearing regeneration. For this, retroviruses are being utilized as mutagens, and high-throughput analyses are being used to map the precise position of retroviral integrations. Akin to P-element mutations in Drosophila, this approach is creating a large zebrafish mutation pool that can be screened for phenotypes relevant to hearing function and inner ear regeneration. Once such mutations are identified, their roles in development, function, and tissue repair can be determined.
By integrating the information emerging from these different projects, a deeper understanding of the underlying network of tissue regeneration in the ear will emerge, potentially providing the basis for developing new therapeutic approaches for human hearing loss.
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Last Updated: May 18, 2014