Peter Koopman

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Peter Anthony Koopman FAA (born 3 December 1959) is an Australian biologist best known for his role in the discovery and study of the mammalian Y-chromosomal sex-determining gene, Sry.[1][2][3][4]

Early life and education[edit]

Peter Anthony Koopman was born on 3 December 1959 in Geelong, Victoria, to Dutch immigrant parents, and raised in the coastal town of Torquay, Victoria. He attended Oberon High School in Geelong, where he was School Captain. He studied science at the University of Melbourne from 1977 to 1979, majoring in genetics, and was a resident of Janet Clarke Hall. He undertook BSc Honours research at the Birth Defects Research Institute (now the Murdoch Children's Research Institute) at the Royal Children's Hospital, Melbourne, under the supervision of Richard (Dick) Cotton, and graduated with First Class Honours.

Continuing to work with Cotton, his PhD focused on stem cell differentiation in vitro. During this time, he also studied Japanese, Fine Arts and Dutch language and literature, receiving a BA degree from the University of Melbourne in 1985.

He was awarded a Doctor of Science (DSc) from the University of Queensland in July 2018.

Career and research[edit]

Discovery of Sry and the genetics of sex determination[edit]

In 1988, Koopman was recruited to the Medical Research Council's National Institute for Medical Research at Mill Hill, London, working first with Anne McLaren, then joining a team led by Robin Lovell-Badge to search for the Y chromosomal sex-determining gene. Koopman demonstrated that activity of mouse homologues of the existing candidate, ZFY, was not consistent with a role in sex determination.[5] Lovell-Badge's team, collaborating with Peter Goodfellow and colleagues at the Imperial Cancer Research Fund in London, discovered a new candidate gene, Sry.[1][6] Koopman and colleagues injected Sry into fertilized XX mouse eggs which as a result developed as males, thus proving the male sex-determining role of Sry.[3] The discovery is regarded as one of the major achievements in molecular genetics in the 20th century.

Much of Koopman's subsequent research has focused on understanding how Sry acts to direct the formation of testes in the embryo, triggering male development. This work has involved the identification and/or study of a large number of other genes involved in development of the testes or ovaries.[7]

Sox genes[edit]

Establishing his own research group[8] at the University of Queensland, Brisbane, Australia in 1992, Koopman set out to discover new members of a growing family of genes related to Sry – "Sox" genes.[9][10] Among the first discoveries was Sox9,[11] a key regulator of skeletal and testis development, which carries mutations in humans with the skeletal disorder campomelic dysplasia and associated XY sex reversal.[12]

Koopman's group also discovered Sox18,[13][14] a switch gene that directs formation of the lymphatic vessels,[15] and is defective in humans with hypotrichosis-lymphedema-telangiectasia syndrome.[16] Given the role of lymphatic vessels in tumour metastasis, Sox18 is being developed as a potential drug target for anti-metastatic cancer therapy.[17]

Koopman found that the human and mouse genomes contain 20 Sox genes,[18] and he proposed the naming system for Sox genes that continues to be used today.[19]

Germ cell sex[edit]

Koopman's early work with Anne McLaren spawned an interest in the regulation of the germ cells during fetal development—cells that later become sperm or oocytes.[20] His group discovered that the vitamin A metabolite retinoic acid stimulates germ cells to enter meiosis, a critical step in the formation of gametes.[21] They also demonstrated that the developmental signaling molecule Nodal and its receptor Cripto regulate male germ cell pluripotency in the fetal gonad,[22] opening the way for new non-invasive diagnostics and targeted additional therapies for testicular cancers.[23]

Intersex advocacy[edit]

With a growing interest in human variations of sex development (alternatively known as DSD, differences or disorders of sex development, variations in sex characteristics, or intersex), Koopman began to engage with relevant clinicians and intersex advocacy and support groups. To cater for a need for unbiased information relating to the causes, types, impacts of DSD and options for affected people, Koopman authored a website, published under the auspices of the Australian National Health and Medical Research Council’s Research Program in Human DSD. He continues to work with the Australian Pediatric Endocrine Group and a range of advocacy groups to improve dialogue and management of these conditions.[24]

Research integrity[edit]

From 2012 to 2017, Koopman worked as the University of Queensland's Executive Director of Research Integrity, providing academic stewardship of research integrity and managing allegations of research misconduct.

Equity and diversity[edit]

Koopman co-chairs the Equity and Diversity Reference Group of the Australian Academy of Science[25] and is a member of the Women in Health Science Working Committee of NHMRC Australia,[26] and is involved in developing the Decadal Plan for Women in STEM[27] commissioned by the Australian Government.

Awards and honours[edit]

1981: First Class Honours, Department of Genetics, The University of Melbourne

1992: AMP Biomedical Research Award, Australian Society for Medical Research

1992: Australian Research Fellowship, Australian Research Council

1998: Julian Wells Medal, Lorne Genome Conference Inc[28]

2002: Australian Professorial Fellowship, Australian Research Council[29]

2003: Amersham-Pharmacia Biotech Medal, Australian Society for Biochemistry and Molecular Biology[30]

2005: President's Medal, Australia and New Zealand Society for Cell and Developmental Biology[31]

2007: Australian Professorial Fellowship, Australian Research Council[32]

2007: Award for Research Excellence, GSK Australia[33]

2008: Fellow of the Australian Academy of Science (FAA)[34]

2009: Lemberg Medal, Australian Society for Biochemistry and Molecular Biology[35]

Other achievements[edit]

Koopman instigated the Australian Developmental Biology Workshop (2001- ), the Australian Sex Summit (2004- ), and the International Workshop on Sox Transcription Factors (2005 - ). He was organizer of the Cold Spring Harbor (USA) Workshop on Molecular Embryology of the Mouse (1995-1998), and Chair of the Gordon Research Conference on Germinal Stem Cell Biology (2017).

Koopman has trained 34 postdoctoral research staff and 28 PhD students. He has published more than 280 research papers that have been cited over 19,000 times.[36]

References[edit]

  1. ^ a b Gubbay, John; Collignon, Jérôme; Koopman, Peter; Capel, Blanche; Economou, Androulla; Münsterberg, Andrea; Vivian, Nigel; Goodfellow, Peter; Lovell-Badge, Robin (July 1990). "A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes". Nature. 346 (6281): 245–250. Bibcode:1990Natur.346..245G. doi:10.1038/346245a0. ISSN 0028-0836. PMID 2374589. S2CID 4270188.
  2. ^ Koopman, Peter; Münsterberg, Andrea; Capel, Blanche; Vivian, Nigel; Lovell-Badge, Robin (November 1990). "Expression of a candidate sex-determining gene during mouse testis differentiation". Nature. 348 (6300): 450–452. Bibcode:1990Natur.348..450K. doi:10.1038/348450a0. ISSN 0028-0836. PMID 2247150. S2CID 4322050.
  3. ^ a b Koopman, Peter; Gubbay, John; Vivian, Nigel; Goodfellow, Peter; Lovell-Badge, Robin (May 1991). "Male development of chromosomally female mice transgenic for Sry". Nature. 351 (6322): 117–121. Bibcode:1991Natur.351..117K. doi:10.1038/351117a0. ISSN 0028-0836. PMID 2030730. S2CID 3331979.
  4. ^ The University of Queensland. "UQ Researchers".
  5. ^ Koopman, Peter; Gubbay, John; Collignon, Jérôme; Lovell-Badge, Robin (December 1989). "Zfy gene expression patterns are not compatible with a primary role in mouse sex determination". Nature. 342 (6252): 940–942. Bibcode:1989Natur.342..940K. doi:10.1038/342940a0. ISSN 0028-0836. PMID 2480529. S2CID 4303582.
  6. ^ Sinclair, Andrew H.; Berta, Philippe; Palmer, Mark S.; Hawkins, J. Ross; Griffiths, Beatrice L.; Smith, Matthijs J.; Foster, Jamie W.; Frischauf, Anna-Maria; Lovell-Badge, Robin (July 1990). "A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif". Nature. 346 (6281): 240–244. Bibcode:1990Natur.346..240S. doi:10.1038/346240a0. ISSN 0028-0836. PMID 1695712. S2CID 4364032.
  7. ^ "UQ eSpace". espace.library.uq.edu.au. Retrieved 10 October 2018.
  8. ^ "Institute for Molecular Bioscience - University of Queensland". Institute for Molecular Bioscience. Retrieved 10 October 2018.
  9. ^ Wright, Edwina M.; Snopek, Bernadette; Koopman, Peter (1993). "Seven new members of theSoxgene family expressed during mouse development". Nucleic Acids Research. 21 (3): 744. doi:10.1093/nar/21.3.744. ISSN 0305-1048. PMC 309180. PMID 8441686.
  10. ^ Koopman P, Bullejos M, Bowles J. (2001). "Regulation of male sexual development by Sry and Sox9". Journal of Experimental Zoology. 290 (5): 463–474. doi:10.1002/jez.1089. PMID 11555853.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ^ Wright, Edwina; Hargrave, Murray R.; Christiansen, Jeffrey; Cooper, Leanne; Kun, Jutta; Evans, Timothy; Gangadharan, Uma; Greenfield, Andy; Koopman, Peter (January 1995). "The Sry-related gene Sox9 is expressed during chondrogenesis in mouse embryos". Nature Genetics. 9 (1): 15–20. doi:10.1038/ng0195-15. ISSN 1061-4036. PMID 7704017. S2CID 22654180.
  12. ^ Foster, Jamie W.; Dominguez-Steglich, Marina A.; Guioli, Silvana; Kwok, Cheni; Weller, Polly A.; Stevanović, Milena; Weissenbach, Jean; Mansour, Sahar; Young, Ian D. (December 1994). "Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene". Nature. 372 (6506): 525–530. Bibcode:1994Natur.372..525F. doi:10.1038/372525a0. ISSN 0028-0836. PMID 7990924. S2CID 1472426.
  13. ^ Hosking, Brett M.; Muscat, George E.O.; Koopman, Peter A.; Dowhan, Dennis H.; Dunn, Timothy L. (1995). "Trans-activation and DNA-binding properties of the transcription factor, Sox-18". Nucleic Acids Research. 23 (14): 2626–2628. doi:10.1093/nar/23.14.2626. ISSN 0305-1048. PMC 307084. PMID 7651823.
  14. ^ Pennisi, David; Gardner, Jennifer; Chambers, Doreen; Hosking, Brett; Peters, Josephine; Muscat, George; Abbott, Catherine; Koopman, Peter (April 2000). "Mutations in Sox18 underlie cardiovascular and hair follicle defects in ragged mice". Nature Genetics. 24 (4): 434–437. doi:10.1038/74301. ISSN 1061-4036. PMID 10742113. S2CID 24013687.
  15. ^ François, Mathias; Caprini, Andrea; Hosking, Brett; Orsenigo, Fabrizio; Wilhelm, Dagmar; Browne, Catherine; Paavonen, Karri; Karnezis, Tara; Shayan, Ramin (19 October 2008). "Sox18 induces development of the lymphatic vasculature in mice". Nature. 456 (7222): 643–647. Bibcode:2008Natur.456..643F. doi:10.1038/nature07391. ISSN 0028-0836. PMID 18931657. S2CID 4416082.
  16. ^ Irrthum, Alexandre; Devriendt, Koenraad; Chitayat, David; Matthijs, Gert; Glade, Conrad; Steijlen, Peter M.; Fryns, Jean-Pierre; Van Steensel, Maurice A. M.; Vikkula, Miikka (June 2003). "Mutations in the Transcription Factor Gene SOX18 Underlie Recessive and Dominant Forms of Hypotrichosis-Lymphedema-Telangiectasia". The American Journal of Human Genetics. 72 (6): 1470–1478. doi:10.1086/375614. ISSN 0002-9297. PMC 1180307. PMID 12740761.
  17. ^ Overman, Jeroen; Fontaine, Frank; Moustaqil, Mehdi; Mittal, Deepak; Sierecki, Emma; Sacilotto, Natalia; Zuegg, Johannes; Robertson, Avril AB; Holmes, Kelly (31 January 2017). "Pharmacological targeting of the transcription factor SOX18 delays breast cancer in mice". eLife. 6. doi:10.7554/elife.21221. ISSN 2050-084X. PMC 5283831. PMID 28137359.
  18. ^ Schepers, Goslik E.; Teasdale, Rohan D.; Koopman, Peter (August 2002). "Twenty Pairs of Sox". Developmental Cell. 3 (2): 167–170. doi:10.1016/s1534-5807(02)00223-x. ISSN 1534-5807. PMID 12194848.
  19. ^ Bowles, Josephine; Schepers, Goslik; Koopman, Peter (November 2000). "Phylogeny of the SOX Family of Developmental Transcription Factors Based on Sequence and Structural Indicators". Developmental Biology. 227 (2): 239–255. doi:10.1006/dbio.2000.9883. ISSN 0012-1606. PMID 11071752.
  20. ^ Koopman P. (2016). "The Curious World of Gonadal Development in Mammals". Current Topics in Developmental Biology. 116: 537–545. doi:10.1016/bs.ctdb.2015.12.009. ISBN 9780128029565. PMID 26970639.
  21. ^ Bowles, Josephine; Knight, Deon; Smith, Christopher; Wilhelm, Dagmar; Richman, Joy; Mamiya, Satoru; Yashiro, Kenta; Chawengsaksophak, Kallayanee; Wilson, Megan J. (28 April 2006). "Retinoid Signaling Determines Germ Cell Fate in Mice". Science. 312 (5773): 596–600. Bibcode:2006Sci...312..596B. doi:10.1126/science.1125691. ISSN 0036-8075. PMID 16574820. S2CID 2514848.
  22. ^ Spiller, Cassy M.; Feng, Chun-Wei; Jackson, Andrew; Gillis, Ad J. M.; Rolland, Antoine D.; Looijenga, Leendert H. J.; Koopman, Peter; Bowles, Josephine (15 November 2012). "Endogenous Nodal signaling regulates germ cell potency during mammalian testis development". Development. 139 (22): 4123–4132. doi:10.1242/dev.083006. ISSN 0950-1991. PMID 23034635.
  23. ^ Spiller, Cassy M.; Bowles, Josephine; Koopman, Peter (2013). "Nodal/Cripto signaling in fetal male germ cell development: implications for testicular germ cell tumors". The International Journal of Developmental Biology. 57 (2–3–4): 211–219. doi:10.1387/ijdb.130028pk. ISSN 0214-6282. PMID 23784832.
  24. ^ Lee, Peter A.; Nordenström, Anna; Houk, Christopher P.; Ahmed, S. Faisal; Auchus, Richard; Baratz, Arlene; Baratz Dalke, Katharine; Liao, Lih-Mei; Lin-Su, Karen (2016). "Global Disorders of Sex Development Update since 2006: Perceptions, Approach and Care". Hormone Research in Paediatrics. 85 (3): 158–180. doi:10.1159/000442975. ISSN 1663-2818. PMID 26820577.
  25. ^ "Committee—Equity and Diversity Reference Group | Australian Academy of Science". www.science.org.au. Retrieved 10 October 2018.
  26. ^ "Women in health science working committee". National Health and Medical Research Council.
  27. ^ "Women in Science, Technology, Engineering and Mathematics (STEM) Decadal Plan | Australian Academy of Science". www.science.org.au. Retrieved 10 October 2018.
  28. ^ "UQ researcher wins medal for excellence in gene research". UQ News. Retrieved 10 October 2018.
  29. ^ "Molecular genetics of mammalian sexual development: Molecular roles of SRY and SOX9 - UQ Researchers". researchers.uq.edu.au. Retrieved 10 October 2018.
  30. ^ "2002 Amersham Pharmacia Biotech Medallist: Professor Peter Koopman". Australian Society for Biochemistry and Molecular Biology. Retrieved 10 October 2018.
  31. ^ "President's Medal » ANZSCDB". www.anzscdb.org. Retrieved 10 October 2018.
  32. ^ "How the Y Chromosome makes a male: Molecular genetic analysis of key sex-determining genes - UQ Researchers". researchers.uq.edu.au. Retrieved 10 October 2018.
  33. ^ "Alumni Members | GSK Australia". Retrieved 10 October 2018.
  34. ^ "Professor Peter Anthony Koopman | Australian Academy of Science". www.science.org.au. Retrieved 10 October 2018.
  35. ^ "Peter Koopman - ASBMB". ASBMB. Retrieved 10 October 2018.
  36. ^ ORCID. "Peter Koopman (0000-0001-6939-0914) - ORCID | Connecting Research and Researchers". orcid.org. Retrieved 10 October 2018.