Stephen J. O'Brien

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Stephen J. O’Brien (born 1944) is an American geneticist. He served as Chief of the Laboratory of Genomic Diversity at the National Cancer Institute (NCI), National Institutes of Health (NIH) from 1986 to 2011. In December 2011, he joined the Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, Russia as Chief Scientific Officer.

O’Brien earned a Ph.D (1971) in genetics at Cornell where he expanded the nascent discipline of biochemical genetics, developing the gene-enzyme maps of Drosophila melanogaster. His biochemical mapping would stimulate his editing of six editions of Genetic Maps: Locus Maps of Complex Genomes (1980–1993) (Cold Spring Harbor Laboratory Publications), international unabridged compendiums of plant, animal, bacteria and virus genetic maps that were prelude to the online NCBI gene mapping databases of species whole genome DNA sequences.[1]

O’Brien is known for his research contributions in comparative genomics, virology, genetic epidemiology, mammalian systematics and species conservation.

In 1983, he and his collaborators discovered the remarkable genetic uniformity of the African cheetah, a prelude to a new discipline of Conservation Genetics.[2][3][4] This has since been disproved by P. Charruau and collaborators.[5] Over three decades of field studies with his students and colleagues, he subsequently reported over 300 conservation related publications, many in the highest rated scientific journals of how genetics could inform and facilitate management action for endangered species.[6] These included genetic studies on cheetahs, lions, tigers, elephants, clouded leopard, orangutans, giant panda, leopards, pumas, jaguars, koalas and humpback whales and many other threatened wildlife species.

In 1982, O’Brien’s team at the NIH published a comprehensive gene map of domestic cat as cover article in SCIENCE[7] and compared genome organization of the cat to human, mouse and other species demonstrating extreme conservation of chromosomal synteny (homologous gene order) between disparate mammalian species. These and subsequent studies (circa 250 publication; many in leading journals) established the field of Comparative Genomics.[8] This discipline today remains a baseline for interpreting the organization and evolution of human and established the domestic cat as a powerful genetic model for hereditary cancer and infections diseases in man and animals. O’Brien is considered by some the leader of the Cat Genome Project.[9]

In 1996 O’Brien’s team described he first human gene to influence HIV-1 infection and AIDS progression, CCR5-∆32, using population genetic based association analysis.[10][11] This discovery has led to several HIV entry inhibitor developments that have been approved by FDA as also stimulated the first real cure of HIV-AIDS in the so-called Berlin patient who permanently cleared HIV when infused with CCR5-∆32/ CCR5-∆32 donor stem cells in 2006. O’Brien’s group used similar genetic association studies to invigorate the field of Genetic Epidemiology, describing over 30 AIDS restriction genes[12] and also applying these gene discovery strategies to chronic infectious human diseases including hepatitis c, hepatitis-B, hepatocellular carcinoma and nasopharyngeal carcinoma.

In 2009 O’Brien joined with David Haussler and Oliver Ryder to found the Genome10K project,[13] an international consortium of genome scientists joined together to facilitate the whole genome sequencing, assembly and annotation of 10,000 vertebrate species by 2015. (http://genome10k.org/)

O’Brien has a strong dedication to education, evidenced by his appointments as adjunct professor at twelve universities: Harvard University, The Johns Hopkins University, Cornell University, Duke University, Peking University-Beijing, University of Maryland, University of Minnesota, Michigan State University, Colorado State University, George Washington University, George Mason University and Hood College of Frederick. He has mentored more than thirteen Ph.D. students including: Roger Reeves, Dennis Gilbert, Robert Wayne, Cheryl Winkler, Jose Lopez, Melanie Culver, Eduardo Eizirik, Olga Uphyrkina, Carlos Driscoll, Meredith Brown, Sriyanie Miththapala, Ann Schmidt-Kuntzel and Shu Jin Luo in addition to eight M.S. theses and over thirty post-doctoral fellows. Since 1996 he has directed an internationally heralded short course sponsored by Smithsonian and American Genetics Association, entitled “Recent Advances in Conservation Genetics”, the most recent (2012) edition at The Smithsonian Tropical Research Institute in Panama.

O’Brien was elected to the American Academy of Arts and Sciences, to the Explorer’s Club and to the Cosmos Club. He served as President of the NIH Assembly of Scientists, as Chairman of the International Committee on Comparative Gene Mapping for the Human Genome Organization (HUGO). O’Brien founded and co-directed New Opportunities in Animal Health Sciences (NOAHS), a consortium of scientists and apprentices, part of the Smithsonian Institution/National Zoological Park, dedicated to applying biomedical technology on behalf of species conservation and to training a generation of conservation scientists. He is the Chairman of the Science Advisory Board for the International BarCode of Life Project and Chairman of the Board of the Cheetah Conservation Fund.

O’Brien is the author or co-author of over 750 scientific articles and the editor of fourteen volumes. In 2004 he published a popular book of science adventure stories entitled “Tears of the Cheetah And Other Tales From The Genetic Frontier” (St. Martin’s Press NYC) [14] In 2007, he published a comprehensive Atlas of Mammalian Chromosomes, a photo-compendium of the karyotype of nearly 1000 species of mammals, (John Wiley Inc. NYC)14. Dr. O’Brien has served as editor of six editions of Genetic Maps: Locus Maps of Complex Genomes (Cold Spring Harbor Laboratory Press); Editor of Journal of Heredity (American Genetics Association) from 1987 to 2007; Editor for Isozyme Bulletin; Associate Editor for Genomics; Human Genomics, Mammalian Genome, Molecular Phylogenetics and Evolution, Cosmos, Annual Review of Animal Biosciences and Annual Review of Genomics and Human Genetics. An unabridged listing and access to his science publications are found on the Dobzhansky Center Web Site: http://dobzhanskycenter.bio.spbu.ru/?page_id=76&lang=en

O’Brien received his B.S. in Biology in 1966 from St. Francis College, which presented him with a Distinguished Alumni Award in 1994. In 1971 he earned a Ph.D. in Genetics from Cornell University which honored him as “Andrew Dixon White Endowed Professor at Large” in 1998. In 2009, he was awarded an honorary Doctorate of Veterinary Medicine from the University of Zurich.

References[edit]

  1. ^ O'Brien, S.J. (Ed.): Genetic Maps, 1987. Cold Spring Harbor Laboratory Press, New York, Vol. 4, 842 pp. (Published 6 editions 1980–1996)
  2. ^ O'Brien, S.J., Wildt, D. E., Goldman, D., Merril, C. R., and Bush, M.: The cheetah is depauperate in genetic variation. Science 221: 459 462, 1983.
  3. ^ O'Brien, S.J., Roelke, M. E., Marker, L., Newman, A., Winkler, C. A., Meltzer, D., Colly, L., Evermann, J. F., Bush, M., and Wildt, D. E.: Genetic basis for species vulnerability in the cheetah. Science 227: 1428 1434, 1985.
  4. ^ O'Brien, S.J., Wildt, D. E., and Bush, M.: The cheetah in genetic peril. Sci. Am. 254: 84-92, 1986
  5. ^ Charruau P, Fernandes C (2011) Phylogeography, genetic structure and population divergence time of cheetahs in Africa and Asia: evidence for long-term geographic isolates. Molecular Ecology, 20, 706–724.
  6. ^ O’Brien, S.J., and Johnson, W.: Big cat genomics. Ann. Rev. Genomic and Human Genetics 6:407-429, 2005.
  7. ^ O'Brien, S.J. and Nash, W. G.: Genetic mapping in mammals: Chromosome map of the domestic cat. Science 216: 257 265, 1982.
  8. ^ O’Brien, S.J., Menotti-Raymond, M., Murphy, W. J., Nash, W. G., Wienberg, J., Stanyon, R., Copeland, N. G., Jenkins, N. A., Womack, J. E., and Marshall Graves, J. A.: The promise of comparative genomics in mammals. Science 286: 458-481, 1999.
  9. ^ O’Brien, S.J., Johnson, W., Driscoll, C., Pontius, J., Pecon-Slattery, J., Menotti-Raymond, M.: State of Cat Genomics. Trends in Genetics 24: 268-279, 2008.
  10. ^ Dean, M., Carrington, M., Winkler, C., Huttley, G.A., Smith, M.W., Allikmets, R., Goedert, J.J., Buchbinder, S.P., Vittinghoff, E., Gomperts, E., Donfield, S., Vlahov, D., Kaslow, R., Saah, A., Rinaldo, C., Detels, R., HGDS, MACS, MHCS, SF City Cohort, ALIVE Study and O’Brien, S.J.: Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Science 273: 1856–1862, 1996.
  11. ^ O’Brien, S.J. and Dean, M.: In search of AIDS-resistance genes. Sci Amer 277: 44-51, Sept. 1997.
  12. ^ O’Brien, S.J. and Nelson, G.W.: Human genes that limit AIDS. Nature Genetics.36:565-574, 2004.
  13. ^ Genome 10K Community of Scientists: A Proposal to Obtain Whole-Genome Sequence for 10,000 Vertebrate Species. J Hered. 2009 Nov–Dec;100(6):659-74.
  14. ^ O’Brien, S.J.: Tears of the Cheetah and Other Tales from the Genetic Frontier, St. Martin’s Press, New York, 2003, pp 273. 14. O’Brien, S.J., Menninger, J. C and Nash, W. G.: An Atlas of Mammalian Genomes. John Wiley & Sons Publishers, New York, NY, 2006.

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