Dr. Segre's research has historically focused on how the epidermis - the exposed layer of the skin - creates a barrier at the interface of the body and the environment. Using animal models, her laboratory explored the genetic pathways involved in building and repairing this skin barrier. They found that, in response to skin perturbations, epidermal cells express high levels of antimicrobial peptides, proteins that can both directly kill microbes (e.g., bacteria and fungi) and stimulate the body's immune system. This observation has led Dr. Segre to shift her research focus to identifying the microbes that inhabit the skin. As the largest organ of the human body, skin serves as a critical barrier to invasion by microbes, while at the same time providing a major home to them.
Dr. Segre's research program is now exploring the bacteria and other microbes that constitute the skin microbiome. Using contemporary genomic methodologies, she is focusing on the role that these microbes may play in human health and disease. The Segre laboratory estimates that approximately one million bacteria reside on each square centimeter of skin; many common skin conditions are associated with both impaired skin barrier function and increased microbial colonization. By sequencing the DNA of bacteria collected from the skin of humans and mouse models of human disease, Dr. Segre's group investigates how these bacteria contribute to health and, conversely, how changes in the bacterial community structure might contribute to chronic skin disorders, such as eczema and psoriasis.
Eczema, also called atopic dermatitis, is characterized by red, itchy patches of skin. Its prevalence has doubled in the United States over the last 30 years, with approximately 15 percent of children and about 2 percent of adults currently affected. Medical management of atopic dermatitis in the United States is associated with an estimated 7.4 million physician visits and over $1 billion in direct costs annually, posing a significant financial and medical burden. Cognizant of this rise in atopic dermatitis incidence and its consequences, Dr. Segre's laboratory has launched a clinical study of the microbiome associated with the skin of eczema patients.
Analysis of microbial diversity has traditionally been based on culturing samples; however, this method detects only a limited fraction of the bacteria that are actually present. New genomic tools are now available that identify bacteria based on species-specific sequences in the 16S rRNA ribosomal genes. In collaboration with clinical dermatologists from the National Cancer Institute, Dr. Segre's group is using such new techniques to perform an initial study to catalog the resident skin microbiota of healthy humans. Initially, the group is collecting samples from the bend of the elbow, which is often affected in patients with eczema. The samples are then analyzed with high-throughput sequencing by the NIH Intramural Sequencing Center (NISC). Many thousands of 16S rRNA sequences are being generated in order to identify both dominant and rare species of bacteria that reside in this area. Many of the bacterial species detected so far were previously unknown to be present on human skin.
Microbial studies are being extended to a broad range of human skin sub-sites, including the navel, the sole of the foot, and the forehead. These skin sub-sites are commonly affected in skin diseases, and are associated with a wide range of physiological properties, including the density of hair follicles and sweat glands. In collaboration with the Microbiology Laboratory of the NIH Clinical Center, Dr. Segre's group is culturing large numbers of aerobic and anaerobic bacteria from these skin sub-sites; she plans to then determine the complete genomic sequence of novel isolates. Sequencing will be performed at NISC using powerful new DNA sequencing platforms. The generation of genome sequences from large numbers of newly-isolated microbes will facilitate downstream studies involving metagenomic analyses of samples from patients with different skin diseases.
Dr. Segre is an active participant in the Human Microbiome Project, an effort launched as part of the NIH Roadmap for Medical Research to comprehensively characterize human microbiota (nihroadmap.nih.gov/hmp).
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Last Updated: May 18, 2014