Julie Segre

Dr. Julie Segre received her B.A. summa cum laude in mathematics from Amherst College, where she now serves on the board of trustees.  She received her Ph.D. in 1996 from the Massachusetts Institute of Technology in the laboratory of Eric Lander, Ph.D., and the newly formed genome center. Dr. Segre then performed postdoctoral training with Elaine Fuchs, Ph.D., an expert in skin biology, at the University of Chicago. 
Dr. Segre joined the National Human Genome Research Institute of NIH in 2000 and was promoted to a senior investigator with tenure in 2007.  Dr. Segre's laboratory utilizes high-throughput sequencing and develops algorithms to track hospital-acquired infections of multi-drug resistant organisms, including the 2011 NIH's multi-drug resistant Klebsiella pneumoniae outbreak. Dr. Segre pioneered the utilization of genome sequencing to articulate the antibiotic resistance potential of Klebsiella pneumoniae and other carbapenem-resistant Enterobacteriaceae, which lead the Centers for Disease Control list of urgent threats. Dr. Segre's laboratory also develops genomic tools to study the microbial diversity of human skin in both health and disease states, with a focus on eczema and other microbial-associated infections. Dr. Segre published the first topographical maps of human skin bacterial and fungal diversity, which empower clinical trials of both common and rare dermatologic disorders. 
Dr. Segre's research is based on active collaborations with the NIH Intramural Sequencing Center and the clinical departments of Infection Control, Microbiology, and Dermatology. Dr. Segre is a leader in the NIH Human Microbiome Project, communicating with multiple media sources to promote the concepts of antibiotic stewardship and humans as ecological landscapes. Segre served as a federal expert for the 2014 PCAST report on antimicrobial resistance. Together with the NIH epidemiologist, Tara Palmore, M.D., Segre received the 2013 Service to America Medal, considered among the most prestigious for a federal employee, for their work to establish the clinical utility of microbial genomics. 

In Good Company: Our Microbial Ecosystem in Health and Disease

Deciphering the genetic material encoded by our 23 human chromosomes has provided tremendous benefit for both diagnoses and directed therapies.  Clinical benefit can also be derived from better management of the bacterial infections associated either directly or indirectly with human disease. We study human health within the perspective that we are super-organisms coexisting with billions of microbiota who live in and on our bodies.

We performed high throughput genomic sequencing surveys to investigate the topographical and temporal complexity of skin microbial communities from 20 skin sites in healthy adults.  Metagenomic analysis of diverse body sites in healthy humans defined the skin microbiome as shaped by the local biogeography, yet marked by strong individuality. This work, which defines the dual influence of biogeography and individuality on microbial composition and function, is foundational for human disease studies investigating inter-kingdom interactions, metabolic changes, and strain tracking.  Our bacterial studies with healthy volunteers set the stage to explore the microbial etiology of the common skin disorder atopic dermatitis (commonly known as eczema), which develops in the first year of life. Based on genome sequence analysis, we propose a model whereby decreased microbial diversity and increased staphylococcal prevalence precede disease exacerbation. Better disease management has the potential to benefit pediatric atopic dermatitis subjects and decrease the severity of associated asthma and hay fever.

Additional microbial genomic studies explore how to better control transmission of hospital acquired infections with multi-drug resistant bacteria. Over six months in 2011, seventeen patients at our institute were colonized with a highly virulent, transmissible carbapenem-resistant strain of Klebsiella pneumoniae (6 patients deaths attributable to infection). For the first time, our real-time genomic sequencing tracked exact patient-to-patient routes of transmission within our institute and informed epidemiologists’ actions to monitor and control this outbreak. More recent studies added another layer of complexity to shape our understanding of outbreak surveillance and infection control; the repertoire of carbapenem-resistance encoding plasmids amongst the patient population and the hospital environment.  Carbapenem-resistant Klebsiella pneumoniae are formidable hospital pathogens that pose a serious threat to patients around the globe due to ~50% mortality rate from infection, undetected transmission between patients, increased incidence in healthcare facilities, and finally, potential to spread antibiotic resistance to other bacterial species, such as Escherichia coli.