Professor Andrew Sinclair
Role:
Deputy Director
Email:
Available for Student Supervision
Professor Andrew Sinclair
Biography:
Professor Andrew Sinclair is Deputy Director of the Murdoch Childrens Research Institute at the Royal Children's Hospital in Melbourne. He is also a Professorial Fellow in the Department of Pediatrics at the University of Melbourne.
Professor Sinclair leads an NHMRC Program focusing on the molecular genetics of gonad development and its impact on patients with disorders of sex development (DSD) and is part of a team awarded a National Centre of Excellence focusing on the regulation of male germ cell differentiation and its impact on infertility and testicular cancer. His contributions have been fundamental to the advancement of the field, including the identification and characterization of the human testis determining gene (SRY) and other genes critical for gonad development. He has also implemented new, accurate, rapid and comprehensive diagnostic procedures to improve outcomes for patients with DSD.
Professor Sinclair has an extensive publication record, including seven Nature papers, with one listed as an ISI citation classic. Altogether his publications have been cited over 6,800 times. While President of the Australian Society for Medical Research in 2004 he led national advocacy efforts seeking increased Federal Government funding for health and medical research. He is an editorial board member of several international journals. Professor Sinclair has received numerous national and international awards including the Outstanding Research Award from the Royal Society UK, the 2009 Sutherland Award for contributions to Human Genetics, and the 2010 Emil Steinberger Memorial Award from the American Society of Andrology. In 2005 he was appointed to the Australian Biotechnology Advisory Council and has chaired the NHMRC Grant Review Panel for Genetics 2007-2008. He was appointed to the NHMRC Assigners Academy for 2011-2013 and the NHMRC Human Genetics Advisory Committee 2009-2015.
Awards:
1987: Smith-White Award, Genetics Society of Australia
1988: Imperial Cancer Research Fellowship award, UK
1990: Outstanding Research Award, Royal Society, UK
1993: NHMRC RD Wright Award
1995: NHMRC Senior Research Fellowship
1998: Distinguished Alumni Award LaTrobe University for outstanding professional achievement and leadership
2000: NHMRC Principal Research Fellowship
2000: Sutherland Award for contributions to Human Genetics (HGSA)
2010: Emil Steinberger Award and Lecturer, American Society for Andrology
2010: David Danks Oration, Deans Lecture Series, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne
Research:
One of the most fundamental influences on our lives is our sex. Whether we are born as male or female has a lifelong impact on our behavioral patterns, personality, reproductive options, disease susceptibility and life expectancy. Not surprisingly, the sex of a newborn child is often the first question asked. When no clear answer can be given, a family and medical emergency follow.
Disorders of Sex Development (DSDs – also known as intersex disorders) are congenital conditions in which development of chromosomal, gonadal or anatomical sex is atypical. They are surprisingly common and represent a significant healthcare burden due to the direct clinical management of these conditions and also their common association with gonadal cancer and infertility. Uncertainty about a child's gender is extremely traumatic for the individual, parents and other family members, and carries profound psychological and reproductive consequences for the patient. The cause of these problems is most often a breakdown of the complex network of gene regulation responsible for proper development of testes or ovaries in the embryo. Studies have identified a small number of genes that play critical roles in testis and ovary development, but efforts to assemble these into a regulatory network have failed, most likely because key pieces of the puzzle are missing.
Professor Andrew Sinclair's research is aimed at identifying the molecular and cellular basis of gonad development and the genetic causes underlying disorders of sex development (DSDs), and applying this knowledge to the diagnosis and clinical management of DSD to improve outcomes for affected children.
Projects:
- Disorders of Sex Development: Genetics, Diagnosis, Informing Clinical Care
- Identification and analysis of regulatory regions associated with Disorders of Sex Development
Western, P.S., Miles, D., van den Bergen, J.A., Burton, M. and Sinclair, A.H. (2008) Dynamic regulation of mitotic arrest in fetal male germ cells. Stem Cells 26:339-347.
Smith, C.A. Roeszler, K. Ohnesorg, T. Farlie, P. and Sinclair, A.H. (2009) The conserved avian Z-linked gene, DMRT1, is required for male sex determination in the chicken. Nature 461:267-271
Western, P.S., van den Bergen, J., Miles, D.C., Sinclair, A.H. (2010) Male fetal germ cell differentiation involves complex repression of the regulatory network controlling pluripotency. FASEB J 24(8):3026-35
Pearlman, A., Loke, J., Le Caignec, C., White, S., Chin, L., Friedman, A., Willan, J., Warr, N., Brauer, D., Brooks, E., Oddoux, C., Riley, B., Shajahan, S., Camerino, G., Homfray, T., Crosby, A., Couper, J., David, A., Greenfield, A., Sinclair, A.H., and Ostrer, H. (2010) Mutations in MAP3K1 cause 46,XY disorders of sex development and implicate a common signal transduction pathway in human testis development. Am J Hum Genet 87: 898- 904
Bagheri-Fam S, Argentaro A, Svingen T, Combes A, Sinclair AH, Koopman P, Harley V (2011) Defective survival of proliferating Sertoli cells and androgen receptor function in a mouse model of the ATR-X syndrome Human Molecular Genetics 20(11): 2213-2224
Sutton, E., Hughes, J., White, S., Tan, J., Rogers, N., Sekido, R., Knower, K., Rowley, L., Eyre, H., Rizzoti, K., Goncalves, J., Slee, J., Turbitt, E., Arboleda, V., Bruno, D., Bengtsson, H., Harley, V., Vilain, E., Sinclair, A.H., Lovell-Badge, R., and Thomas, P. (2011) Identification of Sox3/SOX3 as a XX male sex reversal gene in mice and humans. J Clin Invest 121:328-41
White S, Hewitt J, Turbitt E, Zwan Y, Hersmus R, Drop S, Harley V, Cools M, Looijenga L, Sinclair AH. (2011) A multi-exon deletion within WWOX is associated with a 46,XY Disorders of Sex Development. Eur. J. Hum. Genet. 20(3): 348-351.
White, S., Daggag, H., Ohnesorg, T., Notini, A., Roeszler, K., Turbitt, E., Hewitt, J., Smith, C., Gustin, S., van den Bergen, J., Miles, D., Western, P., Arbodela, V., Gordon, L., Bell, K., Bengtsson, H., Speed, T., Hutson, J., Warne, G., Goncalves, J., Harley, V., Koopman, P., Vilain, E., and Sinclair, A.H. (2011) Copy number variation in patients with disorders of sex development due to gonadal dysgenesis. PLoS One 6(3):e17793
Ayers KL, Davidson NM, Demiyah D, Roeszler KN, Grutzner F, Sinclair AH, Oshlack A, and Smith CA. (2013). RNA sequencing reveals sexually dimorphic gene expression before gonadal differentiation in chicken embryos and allows comprehensive annotation of W-chromosome genes. Genome Biol. 2013 Mar 25;14(3):R26. PMID: 23531366
Eggers, S. Smith, KR. Bahlo, M. Looijenga,L.H.J. Drop,SLS. Juniarto, ZA. Harley, V. Koopman, P. Faradz, SMH. Sinclair AH. (2014) “Whole exome sequencing combined with linkage analysis identifies a novel 3 bp deletion in NR5A1" Eur. J. Hum. Genet doi: 10.1038/ejhg.2014.130
Funding:
- National Health and Medical Research Council Program Grant
- Ian Potter Centre for Genomics and Personalized Medicine
- Helen McPherson Smith Trust Partnership Grant
- National Health and Medical Research Council Project Grant