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The total number of bacteria in the human body is at least ten times greater than the number of human cells, yet the identity and distribution of the microorganisms that constitute these populations are not well understood. More importantly, how these bacteria contribute to, and are affected by, human health is also relatively understudied, not because of an under appreciation of the impact that these organisms may have, but because the strategies and tools necessary to study these populations have not been not available until recently. Some progress to catalog and characterize these organisms and genes has been made in recent years, but most studies have focused on a single body site.  Recent advances in DNA sequencing technologies have enabled more comprehensive analyses of the human microbiota and its role in human health, and it was proposed that a concerted effort leveraging these technologies would increase the understanding of the microbial communities, or “microbiomes” that inhabit various niches within the human body. The newest DNA sequencing platforms make it possible to sequence the DNA of the collective genome (or metagenome) of entire communities of microbes from all body sites, effectively enabling the characterization of the “Human Microbiome”.

Since 2007, my laboratory has been participating in the NIH Roadmap for Medical Research Project called the Human Microbiome Project (HMP) (http://nihroadmap.nih.gov/hmp/). The overarching goal of the HMP is to develop tools and resources for characterization of the human microbiota and to relate these microbiota to human health and disease.  In collaboration with the Human Genome Sequencing Center (HGSC),  a primary focus in my laboratory has been the sequencing and annotation of hundreds of bacterial “reference” genomes to contribute to a catalog of strains (http://www.hmpdacc.org/reference_genomes.php) that is being used as a database against which metagenomic data from human samples can be compared. We have constructed and continue to formulate “mock communities” of organisms and nucleic acids for benchmarking nucleic acid extractions and new uses of Next Generation sequencing technologies for sequencing and analysis of metagenomic data. These have been used for metagenomic analyses by numerous institutions involved in the project. We are also closely collaborating with several groups investigating the relationship between gut microbiota and diseases specifically travelers’ diarrhea and inflammatory bowel disease.

Recent Publications (PubMed)

• The NIH Human Microbiome Project Jumpstart Consortium (2009) A catalog of reference genomes from the Human Microbiome. Science submitted
• Chain, P.S. G., D.V. Grafahm, R. S. Fulton, M.G. FitzGerald, J. Hostetler, D. Muzny, J.C. Detter, J. Ali, B. Birren, T.S. Brettin, D.C. Bruce, C. Buhay, J.R. Cole, Y. Ding, D. Field, G.M. Garrity, R.A. Gibbs, T. Graves, C.S. Han, S.H. Harrison, S. Highlander, M. Holder, P. Hugenholtz, H.M. Khouri, N.C. Kyrpides, D. Lang, A. Lapidus, S.A.Malfatt, K.E. Nelson, J. Parkhill, J. Petrosino, S. Pitluck, X. Qin, T.D. Read, J. Schmutz, S. Sozhamannan, R. Strausberg, G. Sutton, N.R. Thomson, J.M. Tiedje, G. Weinstock, A. Wollam and the entire GSC and HMP Jumpstart consortia (2009) Genome project standards in a new era of sequencing. Science. 326:236-237.
• Petrosino, Joseph F., Sarah Highlander, Ruth Ann Luna, Richard A. Gibbs and James Versalovic (2009) Metagenomic pyrosequencing and microbial identification. Clin. Chem. 55:856-866.
• Bourgogne, Agathe Bourgogne, Danielle A. Garsin, Xiang Qin, Kavindra V Singh, Jouko Sillanpaa, Shailaja Yerrapragada, Yan Ding, Shannon Dugan-Rocha, Christian Buhay, Hua Shen, Guan Chen, Gabrielle Williams, Donna Muzny, Arash Maadani, Kristina A Fox, Jason Gioia, Lei Chen, Yue Shang, Cesar A. Arias, Sreedhar R. Nallapareddy, Meng Zhao, Vittal P. Prakash, Shahreen Chowdhury, Huaiyang Jiang, Richard A. Gibbs, Barbara E Murray, Sarah K. Highlander and George M. Weinstock (2008) Large scale variation in Enterococcus faecalis illustrated by the genome analysis of strain OG1RF. Genome Biology 9:R110.
• Highlander, Sarah K., Kristina G. Hultén, Xiang Qin, Huaiyang Jiang, Shailaja Yerrapragada, Edward O. Mason, Jr., Yue Shang, Tiffany M. Williams, Régine M. Fortunov, Yamei Liu, Okezie Igboeli, Joseph Petrosino, Madhan Tirumalai, Akif Uzman, George E, Fox, Ana Maria Cardenas, Donna M. Muzny, Lisa Hemphill, Yan Ding, Shannon Dugan, Peter R. Blyth, Christian J. Buhay, Huyen H. Dinh, Alicia C. Hawes, Michael Holder, Christie L. Kovar, Sandra L. Lee, Wen Liu, Lynne V. Nazareth, Qiaoyan Wang, Jianling Zhou, Sheldon L. Kaplan, and George M. Weinstock (2007) Subtle genetic changes enhance virulence of methicillin resistant and sensitive strains of Staphylococcus aureus. BMC Microbiol. 6:99-113.
• Gioia, Jason, Shailaja Yerrapragada, Xiang Qin, Huaiyang Jiang, Okezie C. Igboeli, Donna Muzny, Shannon Dugan-Rocha, Yan Ding, Alicia Hawes, Wen Liu, Lesette Perez, Christie Kovar, Huyen Dinh, Sandra Lee, Lynne Nazareth, Peter Blyth, Michael Holder, Christian Buhay, Madhan R. Tirumalai, Yamei Liu, Indrani Dasgupta, Lina Bokhetache, Masaya Fujita, Fathi Karouia, Prahathees Eswara Moorthy, Johnathan Siefert, Akif Uzman, Prince Buzumbo, Avani Verma, Hiba Zwiya, Brian D. McWilliams, Adeola Olowu, Kenneth D. Clinkenbeard, David Newcombe, Lisa Golebiewski, Joseph F. Petrosino, Wayne L. Nicholson, George E. Fox, Kasthuri Venkateswaran, Sarah K. Highlander, George M. Weinstock (2007) Paradoxical DNA Repair and Peroxide Resistance Gene Conservation in Bacillus pumilus SAFR-032. PLoS ONE 2:e928.
• Karpathy, Sandor Qin Xiang, Jason Gioia, Huaiyang Jiang, Yamie Liu, Joseph F. Petrosino, Shailaja Yerrapragada, George E. Fox, Susan Kinder Haake, George M. Weinstock, and Sarah K. Highlander (2007) Genome sequence of Fusobacterium nucleatum subspecies polymorphum - a genetically tractable Fusobacteria. PLoS ONE 2:e659.