Carolyn J. Brown
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Carolyn J. Brown (born in 1961,
Ontario Ontario ( ; ) is one of the thirteen provinces and territories of Canada.Ontario is located in the geographic eastern half of Canada, but it has historically and politically been considered to be part of Central Canada. Located in Central Ca ...
) is a Canadian geneticist and Professor in the Department of Medical Genetics at the
University of British Columbia The University of British Columbia (UBC) is a public university, public research university with campuses near Vancouver and in Kelowna, British Columbia. Established in 1908, it is British Columbia's oldest university. The university ranks a ...
. Brown is known for her studies on
X-chromosome inactivation X-inactivation (also called Lyonization, after English geneticist Mary Lyon) is a process by which one of the copies of the X chromosome is inactivated in therian female mammals. The inactive X chromosome is silenced by being packaged into ...
, having discovered the human XIST gene in 1990.


Education and early career

Brown received her Bachelor of Science in
Genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar wor ...
in 1983 from the
University of Guelph , mottoeng = "to learn the reasons of realities" , established = May 8, 1964 ()As constituents: OAC: (1874) Macdonald Institute: (1903) OVC: (1922) , type = Public university , chancellor ...
, Ontario. She started her PhD thesis work at the
University of Toronto The University of Toronto (UToronto or U of T) is a public research university in Toronto, Ontario, Canada, located on the grounds that surround Queen's Park. It was founded by royal charter in 1827 as King's College, the first institution ...
in 1983, under the supervision of Hunt Willard, and concluded it at
Stanford University Stanford University, officially Leland Stanford Junior University, is a private research university in Stanford, California. The campus occupies , among the largest in the United States, and enrolls over 17,000 students. Stanford is consider ...
, following the moving of Willard’s laboratory in 1989. Brown initiated the studies of the
X chromosome The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and XO sex-d ...
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 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. Willard has referred to Brown as "the critical individual who transformed the study of X inactivation". Brown became Research Associate in 1990 in the Stanford Department of Genetics, and two years later moved with Willard’s laboratory to the Department of Genetics of
Case Western Reserve University Case Western Reserve University (CWRU) is a private research university in Cleveland, Ohio. Case Western Reserve was established in 1967, when Western Reserve University, founded in 1826 and named for its location in the Connecticut Western Reser ...
, Ohio, 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 The University of British Columbia (UBC) is a public university, public research university with campuses near Vancouver and in Kelowna, British Columbia. Established in 1908, it is British Columbia's oldest university. The university ranks a ...
, in Vancouver, and was promoted to Professor in 2004. She 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 the
X-chromosome inactivation X-inactivation (also called Lyonization, after English geneticist Mary Lyon) is a process by which one of the copies of the X chromosome is inactivated in therian female mammals. The inactive X chromosome is silenced by being packaged into ...
process in humans. 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 sequence A regulatory sequence is a segment of a nucleic acid molecule which is capable of increasing or decreasing the expression of specific genes within an organism. Regulation of gene expression is an essential feature of all living organisms and vir ...
s of human XIST and mouse Xist. Her lab has been cataloging escape genes using both expression and
DNA methylation DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts t ...
analysis r to determine which genes contribute to sex differences in disease susceptibility, and which regions of DNA are susceptible to, or resistant to,
epigenetic In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
gene silencing. Since human
embryonic stem cells Embryonic stem cells (ESCs) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre- implantation embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they co ...
are epigenetically unstable, Brown and colleagues have developed alternative model systems to study human inactivation, including inducible XIST transgenes in human
somatic cells A somatic cell (from Ancient Greek σῶμα ''sôma'', meaning "body"), or vegetal cell, is any biological cell forming the body of a multicellular organism other than a gamete, germ cell, gametocyte or undifferentiated stem cell. Such cells compo ...
, human
somatic cell hybrids Somatic may refer to: * Somatic (biology), referring to the cells of the body in contrast to the germ line cells ** Somatic cell, a non-gametic cell in a multicellular organism * Somatic nervous system, the portion of the vertebrate nervous syst ...
retaining the active or the inactive X chromosome, and mouse cells with X-linked
transgene A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change the ...
s of human DNA. Her lab collaborates with other research groups at the B. C. Children’s Hospital and the
BC Cancer Agency BC Cancer is part of the Provincial Health Services Authority in British Columbia, Canada. Facilities BC Cancer's first cancer treatment centre (then known as the British Columbia Cancer Institute) officially opened in Vancouver on November 5, ...
to investigate the clinical relevance of X-linked inactivation and expression in disease predisposition, cancer progression, and X-linked diseases, chromosome rearrangements and
aneuploidies Aneuploidy is the presence of an abnormal number of chromosomes in a cell, for example a human cell having 45 or 47 chromosomes instead of the usual 46. It does not include a difference of one or more complete sets of chromosomes. A cell with any ...
.


Awards and honors

* 1983-1987:
NSERC The Natural Sciences and Engineering Research Council of Canada (NSERC; french: Conseil de recherches en sciences naturelles et en génie du Canada, CRSNG) is the major federal agency responsible for funding natural sciences and engineering rese ...
1967 Centennial Graduate Scholarship * 1988: Pre-doctoral Basic Science Presentation Award from the
American Society of Human Genetics The American Society of Human Genetics (ASHG), founded in 1948, is a professional membership organization for specialists in human genetics. As of 2009, the organization had approximately 8,000 members. The Society's members include researchers, a ...
* 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

{{DEFAULTSORT:Brown, Carolyn, J. 1961 births Living people Canadian geneticists Canadian women geneticists Academic staff of the University of British Columbia University of Guelph alumni University of Toronto alumni Stanford University alumni