Carolyn J. Brown

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Carolyn J. Brown
File:Carolyn J. Brown and her cat Helix.jpeg
Alma materUniversity of Guelph, BA
University of Toronto, PhD
Stanford University, PhD
Scientific career
FieldsHuman Genetics, Epigenetics, X-inactivation
Academic advisorsHunt Willard
WebsiteLab webpage
University webpage

Carolyn J. Brown (born in 1961, Ontario) is a Canadian geneticist and Professor in the Department of Medical Genetics at the University of British Columbia. Brown is renowned for her studies on X-chromosome inactivation, having discovered the human XIST gene in 1990.

Education and early career

Brown received her Bachelor of Science in Genetics in 1983 from the University of Guelph, Ontario. Brown started her PhD thesis work at the University of Toronto, in 1983, under the supervision of Hunt Willard, and concluded it at Stanford University, following the moving of Willard’s laboratory in 1989. Brown initiated the studies of the X chromosome in the lab, and her PhD thesis was entitled “Studies of Human X-Chromosome Inactivation”. Her work involved the analysis of genes that “escape” X-chromosome inactivation, being expressed from the (otherwise) inactive X chromosome, as well as the molecular characterization of the X-inactivation center, the genetic locus that is necessary for silencing of the chromosome. These two topics converged in the 1990 discovery of the XIST gene, which localizes to the X-inactivation center and is expressed solely from the inactive X chromosome. This discovery was reported in two papers in Nature in 1991.[1][2] Willard has referred to Brown as "the critical individual who transformed the study of X inactivation".[3] Brown became Research Associate in 1990, in the Department of Genetics of Stanford University, and two years later moved to the Department of Genetics of Case Western Reserve University , Ohio, with Willard’s laboratory, where she continued studying the XIST long noncoding RNA. Brown became Assistant Professor (1994) and Associate Professor (1999) in the Department of Medical Genetics of the University of British Columbia, in Vancouver, where she currently holds a Professor position since 2004. Brown was the Head of the Department from 2011 to 2014. She has supervised over twenty postdoctoral fellows and graduate students in her laboratory.

Research

Brown’s research is directed to understanding the X-chromosome inactivation process in humans, and her lab has identified critical differences between mouse and human X-chromosome inactivation, such as the absence of paternal X inactivation in human extraembryonic tissues, the higher proportion of human “escapees” and the identification of different regulatory sequences of human XIST and mouse Xist. [4][5]The Brown lab has been cataloging escape genes using both expression and DNA methylation analysis in order to determine which genes might contribute to sex differences in disease susceptibility as well as which regions of DNA are susceptible to, or resistant to, epigenetic gene silencing.[6][7][8][9] Given that human embryonic stem cells are epigenetically unstable, Brown and colleagues have developed several alternative model systems to study human inactivation, including inducible XIST transgenes in human somatic cells, human somatic cell hybrids retaining the active or the inactive X chromosome, and mouse cells with X-linked transgenes of human DNA. [10] In addition, the Brown lab collaborates with research groups at the B. C. Children’s Hospital and the BC Cancer Agency to investigate the clinical relevance of X-linked inactivation and expression in disease predisposition, cancer progression and X-linked diseases, chromosome rearrangements and aneuploidies.[11][12][13][14][15][16]

Awards and honors

  • 1983-1987: NSERC 1967 Centennial Graduate Scholarship
  • 1988: Pre-doctoral Basic Science Presentation Award from the American Society of Human Genetics
  • 1995-2000: MRC Scholarship
  • 1999: Departmental Teaching Award
  • 2001: Early Career Scholar, Peter Wall Institute for Advanced Studies, UBC
  • 2008: UBC Killam Teaching Prize
  • 2018: Canadian College of Medical Genetics Honorary Affiliate

References

Scholia has an author profile for Carolyn J. Brown.
  1. ^ Brown, Carolyn J.; Ballabio, Andrea; Rupert, James L.; Lafreniere, Ronald G.; Grompe, Markus; Tonlorenzi, Rossana; Willard, Huntington F. (1991). "A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome". Nature. 349 (6304): 38–44. Bibcode:1991Natur.349...38B. doi:10.1038/349038a0. PMID 1985261.
  2. ^ Brown, Carolyn J.; Lafreniere, Ronald G.; Powers, Vicki E.; Sebastio, Gianfranco; Ballabio, Andrea; Pettigrew, Anjana L.; Ledbetter, David H.; Levy, Elaine; Craig, Ian W.; Willard, Huntington F. (1991). "Localization of the X inactivation centre on the human X chromosome in Xq13". Nature. 349 (6304): 82–84. Bibcode:1991Natur.349...82B. doi:10.1038/349082a0. PMID 1985270.
  3. ^ Willard, Huntington F. (2010). "2009 William Allan Award Address: Life in the Sandbox: Unfinished Business". The American Journal of Human Genetics. 86 (3): 318–327. doi:10.1016/j.ajhg.2010.01.037.
  4. ^ Yen, Z. C.; Meyer, I. M.; Karalic, S.; Brown, C. J. (2007). "A cross-species comparison of X-chromosome inactivation in Eutheria". Genomics. 90 (4): 453–63. doi:10.1016/j.ygeno.2007.07.002. PMID 17728098.
  5. ^ Chang, S. C.; Brown, C. J. (2010). "Identification of regulatory elements flanking human XIST reveals species differences". BMC Molecular Biology. 11: 20. doi:10.1186/1471-2199-11-20. PMC 2841178. PMID 20211024.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  6. ^ Kutsche, R.; Brown, C. J. (2000). "Determination of X-chromosome inactivation status using X-linked expressed polymorphisms identified by database searching". Genomics. 65 (1): 9–15. doi:10.1006/geno.2000.6153. PMID 10777660.
  7. ^ Cotton, A. M.; Lam, L.; Affleck, J. G.; Wilson, I. M.; Peñaherrera, M. S.; McFadden, D. E.; Kobor, M. S.; Lam, W. L.; Robinson, W. P.; Brown, C. J. (2011). "Chromosome-wide DNA methylation analysis predicts human tissue-specific X inactivation". Human Genetics. 130 (2): 187–201. doi:10.1007/s00439-011-1007-8. PMC 3132437. PMID 21597963.
  8. ^ Cotton, A. M.; Ge, B.; Light, N.; Adoue, V.; Pastinen, T.; Brown, C. J. (2013). "Analysis of expressed SNPs identifies variable extents of expression from the human inactive X chromosome". Genome Biology. 14 (11): R122. doi:10.1186/gb-2013-14-11-r122. PMC 4053723. PMID 24176135.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  9. ^ Cotton, A. M.; Price, E. M.; Jones, M. J.; Balaton, B. P.; Kobor, M. S.; Brown, C. J. (2015). "Landscape of DNA methylation on the X chromosome reflects CpG density, functional chromatin state and X-chromosome inactivation". Human Molecular Genetics. 24 (6): 1528–39. doi:10.1093/hmg/ddu564. PMC 4381753. PMID 25381334.
  10. ^ Tinker, A. V.; Brown, C. J. (1998). "Induction of XIST expression from the human active X chromosome in mouse/human somatic cell hybrids by DNA demethylation". Nucleic Acids Research. 26 (12): 2935–40. PMC 147638. PMID 9611238.
  11. ^ Dawson, A. J.; Wickstrom, D. E.; Riordan, D.; Cardwell, S.; Casey, R.; Baldry, S.; Brown, C. (2004). "A unique patient with an Ullrich-Turner syndrome variant and mosaicism for a tiny r(X) and a partial proximal duplication 1q". American Journal of Medical Genetics. Part A. 124A (3): 303–6. doi:10.1002/ajmg.a.20302. PMID 14708105.
  12. ^ Gibb, E. A.; Vucic, E. A.; Enfield, K. S.; Stewart, G. L.; Lonergan, K. M.; Kennett, J. Y.; Becker-Santos, D. D.; MacAulay, C. E.; Lam, S.; Brown, C. J.; Lam, W. L. (2011). "Human cancer long non-coding RNA transcriptomes". PLOS ONE. 6 (10): e25915. Bibcode:2011PLoSO...625915G. doi:10.1371/journal.pone.0025915. PMC 3185064. PMID 21991387.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  13. ^ Cheung, K. J.; Johnson, N. A.; Affleck, J. G.; Severson, T.; Steidl, C.; Ben-Neriah, S.; Schein, J.; Morin, R. D.; Moore, R.; Shah, S. P.; Qian, H.; Paul, J. E.; Telenius, A.; Relander, T.; Lam, W.; Savage, K.; Connors, J. M.; Brown, C.; Marra, M. A.; Gascoyne, R. D.; Horsman, D. E. (2010). "Acquired TNFRSF14 mutations in follicular lymphoma are associated with worse prognosis". Cancer Research. 70 (22): 9166–74. doi:10.1158/0008-5472.CAN-10-2460. PMID 20884631.
  14. ^ Johnson, N. A.; Al-Tourah, A.; Brown, C. J.; Connors, J. M.; Gascoyne, R. D.; Horsman, D. E. (2008). "Prognostic significance of secondary cytogenetic alterations in follicular lymphomas". Genes, Chromosomes & Cancer. 47 (12): 1038–48. doi:10.1002/gcc.20606. PMID 18720523.
  15. ^ Hatakeyama, C.; Anderson, C. L.; Beever, C. L.; Peñaherrera, M. S.; Brown, C. J.; Robinson, W. P. (2004). "The dynamics of X-inactivation skewing as women age". Clinical Genetics. 66 (4): 327–32. doi:10.1111/j.1399-0004.2004.00310.x. PMID 15355435.
  16. ^ Beever, C. L.; Stephenson, M. D.; Peñaherrera, M. S.; Jiang, R. H.; Kalousek, D. K.; Hayden, M.; Field, L.; Brown, C. J.; Robinson, W. P. (2003). "Skewed X-chromosome inactivation is associated with trisomy in women ascertained on the basis of recurrent spontaneous abortion or chromosomally abnormal pregnancies". American Journal of Human Genetics. 72 (2): 399–407. doi:10.1086/346119. PMC 379232. PMID 12497247.
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