Biography:

Stephen J. O'Brien trained in molecular and population genetics at Cornell University under the mentorship of Bruce Wallace and Ross MacIntyre. He joined the National Cancer Institute as a post-doc in 1971 and is now chief of the NCI's Laboratory of Genomic Diversity, which he founded in the late 1980s. His is known for documenting the remarkable genetic uniformity of African cheetahs, resolving the taxonomic riddle of the giant panda's evolutionary origins and for describing heretofore unrecognized species of orangutans, African forest elephants and Bornean clouded leopards. He is credited with the discovery of CCR5 delta 32, the first of twenty human AIDS restriction genes, as well as leading the Feline Genome Project, a major player in comparative genomics across the mammalian radiations. The Laboratory of Genomic Diversity has assembled over 62,000 animal and 424,000 human tissue/DNA specimens, facilitating wide- ranging studies of disease gene associations, species adaptation and natural history by O'Brien's many colleagues.

Research:

The Laboratory of Genomic Diversity (LGD) was established by NCI in 1986 to establish a research concentration on population-based disease gene discovery in human cohorts and animal models. The Laboratory emphasizes research, characterization, and patient-translation of genetic variants that influence complex and multi-factorial human diseases, particularly cancers, and scourges caused by infectious agents.  Cohort-based genetic association analysis of selected gene families (e.g., HLA , natural killer receptor gene complex, KIR , ABC transporter genes, cytokine, chemokines and their receptors) are combined with genome scanning approaches to discover operative disease influencing alleles.  Where identification of genetic influence on disease points to specific disease mechanisms we seek patient translation of these results by therapeutic agents or approaches targeting these mechanisms.

The comparative genomic effort of the LGD applies multi-species genomic data to annotate the human genome sequence and to discover naturally occurring adaptive genetic defenses against cancers, infectious diseases and hereditary syndromes.  LGD research has implemented the discipline of comparative genomic annotation on sequences nominated for a score of mammals.  This process of comparative inference makes a fundamental contribution towards transforming the human genome sequence into an informative clinical disease database. An ancillary goal is to describe adaptive genetic defenses against deadly diseases, discoveries in mammalian species with the potential of informing better diagnostics, prevention, prognostics, vaccine and therapy development in humankind.

Books:

Tears of the Cheetah: And Other Tales from the Genetic Frontier (Hardcover)
by Stephen J. O'Brien. Publisher: St. Martins Press, NYC (2003)

Atlas of Mammalian Chromosomes (Hardcover)
Edited by: Stephen J. O'Brien, William G. Nash, Joan C. Menninger. Publisher: Wiley-Liss (2006)

Publications:

Hutchenson, H.B., Lautenberger, J.A., Nelson, G.W., Pontius, J.U., Winkler, C.A., Smith, M.W., Johnson, R., Stephens, R., Phair, J., Goedert, J., Donfield, S., O'Brien, S.J.:  Detecting AIDS Restriction Genes: From Candidate Genes to Genome-Wide Association Discovery. Submitted.  Supplemental Figures.

Luo, S.-J., Kim, J.-H., Johnson, W.E., van der Walt, J., Martenson, J., Yuhki, N., Miquelle, D.G., Uphyrkina, O., Goodrich, J.M., Quigley, H.B., Tilson, R., Brady, G., Martelli, P., Subramaniam, V., McDougal, C., Hean, S., Huang, S.-Q., Pan, W., Karanth, U.K., Sunquist, M., Smith, J.L.D., and O'Brien, S.J. :Phylogeography and genetic ancestry of tigers ( Panthera tigris ). PLoS Biology 2:2277-2293, 2004. [ PDF ]

O'Brien, S.J. and Nelson, G.W .: Human genes that limit AIDS. Nature Genetics.36:565-574, 2004. [ PDF ]

Troyer, J., Pecon-Slattery, J. and Roelke-Parker, M., Johnson, W., VandeWoude, S., Vazquez-Salat, Nuria, Brown, M., Frank, L., Woodroffe, R., Winterbach, C., Winterbach, H., Hemson, G., Bush, M., Alexander, K.A., Revilla, E., and O'Brien, S.J .: Seroprevalence and genomic diversity of circulating strains of feline immunodeficiency virus among Felidae and Hyaenidae species. J Virol. 79:8282- 8294. 2005. [ PDF ]

Johnson, W.E., Eizirik, E., Murphy, W.J., Pecon-Slattery, J., Antunes, A., Teeling, E. and O'Brien, S.J. : The late Miocene radiation of modern felidae: A genetic assessment. Science.311:73-77. 2006. [ PDF ]

Teeling, E., Springer, M.S., Madsen, O., Bates, P., O'Brien, S.J., and Murphy, W.J .: A molecular phylogeny for bats illuminates biogeography and the fossil record. Science 307:580-584, 2005. [ PDF ]

Buckley-Beason, V.A., Johnson, W.E., O'Brien, S.J .: Molecular Evidence for Species-Level Distinctions in Clouded Leopards. Current Biol 16:2371-2376, 2006. [ PDF ]

O'Brien, S.J., and Johnson, W .: Big cat genomics. Ann. Rev. Genomic and Human Genetics 6:407- 429, 2005.

Smith, M.W., O'Brien, S.J .: Mapping by Admixture Disequilibrium: Advances, Limits and Guidelines. Nature Genetics Reviews. 6:623-632, 2005. [ PDF ]

Pontius J. U. Mullikin, J. C. Smith, D. Lindblad-Toh, K. Gnerre, S., Clamp, M., Stephens, R., Neelam, B., Volfovsky, N., Schäffer, A. A., Agarwala, R., Narfström K., Murphy, W. J., Giger, U., Roca , A. L., O'hUigin, C., Antunes, A., Menotti-Raymond, M., Yuhki, N., Pecon-Slattery, J., Johnson, W. E., Driscoll, C. and O'Brien, S. J.: The Domestic Cat Genome Sequence: Annotation and Comparative Inferences. Submitted

Driscoll, C. A., Yamaguchi, N., Roca , A. L., Menotti-Raymond, M., Pontier, D., Kitchener, A.,O'Brien, S. J., MacDonald, D.: Near Eastern Origins of Cat Domestication.. Submitted.

O'Brien, S. J. and Johnons, W. E.: Origins of the World's Cats. Scientific American . In Press

Menotti-Raymond, M., David, V. A., Schäffer, A. A., Stephens, R., Kumar-Singh, R., O'Brien, S. J., Narfström, K: CEP290 Mutation Identified in Model of Retinal Degeneration Journal of Heredity-In press.

Martin, M. P., Qi, Y., Gao, X-J., Brown, E. E., Phair, J., Goedert, J. J., Buchbinder, S., Kirk, G. D., O'Brien, S.J., Parham, P., McVica. E. W., Carrington, M.: Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1. Nat Genet In Press.

O'Brien, S.J , An interview with. Q&A. Curr Biol . 17: R152-R154, 2007

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