DEVELOPMENT AND HUMAN DISEASE
Research Focus
Our lab uses the Drosophila and zebrafish genetic model organisms to study
the function of genes and pathogenic processes involved in human disease. The
major genes of interest are those associated with chromosomal fragile sites
that have been implicated in cancer cell biology and the genes in which expanded
repeat give rise to neurodegenerative disease.
The function of the WWOX that spans the common chromosomal
fragile site
In this project we are making use of Drosophila to undertake a genetic approach
to elucidatie gene function. We have targeted the Drosophila orthologue of the
WWOX gene, which in humans spans the FRA16D common chromosomal fragile site.
The FRA16D fragile site has been found to exhibit various forms of instability
in cancer. By identifying the normal role of the WWOX gene we hope to understand
how perturbing this function can contribute to cancer cell biology.
The normal role of the huntingtin protein
This protein contains a repeat that when expanded gives rise to Huntington's
Disease. The protein is widely expressed but the disease exhibits selective
cellular sensitivity. We are using the zebrafish system to look at the developmental
consequences of ablating huntingtin expression. The aim of this work is to determine
whether the normal function of the huntingtin protein is responsible for the
cellular specificity of the disease.
Recent publications
Collaborators & Linkages
'Role of huntingtin and FOR/WWOX in pathogenesis and development'
- Dr Michael Lardelli, School of Molecular and Biomedical Sciences, University
of Adelaide, SA
'Fragile Sites and Chromosomal Instability in Cancer'
- Dr Deon Venter, Peter MacCallum Cancer Institute, East Melbourne, Victoria,
Australia
- Dr Georgia Chenevix-Trench, Queensland Institute of Medical Research, RBH,
Brisbane, Qld
- Professor Rob Saint, Research School of Biological Sciences, ANU, Canberra,
ACT
- Dr Grant Booker, School of Molecular and Biomedical Sciences, University
of Adelaide, SA
- Dr NanShan Chang, Guthrie Institute, Sayre, Pennsylvania, USA
- Dr Catherine Freudenreich, Tufts University, Medford, Massachusetts, USA
'Pseudoxanthoma Elasticum'
- Dr Berthold Struk, Harvard University, Boston, USA
- Professor Klaus Lindpaintner, Roche Genetics, Basel, Switzerland
ARC/NHMRC Research Network in Genes
and Environment in Development (NGED)
Discipline of Genetics,
University of Adelaide
Recent Publications
O'Keefe, L.V., Richards, R.I. (2006) Common chromosomal fragile sites in cancer:
focus on FRA16D. Cancer Letters 232: 37-47
O'Keefe, L., Liu, Y-H., Perkins, A., Dayan, S., Saint, R., and Richards, R.I.
(2006) Corrigendum : FRA16D common chromosomal fragile site oxido-reductase
(FOR/WWOX) protects against the effects of ionising radiation in Drosophila.Oncogene
25: 7662.
Richards, R.I. (2006) Chromosomal fragile sites: mechanisms of cytogenic expression
and pathogenic consequences. In: Genetic Instabilities and Hereditary Neurological
Diseases, Volume 2, R. Wells and T Ashizawa eds. Chapter 12, pages 195-207.Academic
Press 2006.
Tucker, B., Richards, R.I., Lardelli, M. (2006) Contribution of mGluR and Fmr1
functional pathways to neurite morphogenesis, craniofacial development and fragile
X syndrome. Human Molecular Genetics 15: 3446-58
Finnis, M., Dayan, S., Hobson, L., Chenevix-Trench, G., Friend, K., Ried, K.,
Venter, D., Woollatt, E., Baker, E., Richards, R.I. (2005) Common chromosomal
fragile site FRA16D mutation in cancer cells. Human Molecular Genetics 14: 1341-9
McLeod, C.J., O'Keefe, L.V., Richards, R.I. (2005) The pathogenic agent in Drosophila
models of 'polyglutamine' diseases. Human Molecular Genetics 14:1041-8
Miksch, S., Lumsden, A. L., Guenther, U.P., Foernzler, , D., Christen-Zäch,
S., Daugherty , C., Ramesar, R., Lebwohl, M., Thierfelder, L., Hohl, D., Neldner
K.H., Lindpaintner, K., Richards, R.I., and Struk, B. (2005) Molecular Genetics
of Pseudoxanthoma Elasticum : Types and Frequencies of Mutation in ABCC6. Human
Mutation 26: 235-48
O'Keefe, L.V., Richards, R.I. (2005) Common Chromosomal Fragile Sites in Cancer:
Focus on FRA16D. Cancer Letters Oct 19; [Epub ahead of print] PMID: 16242840
Richards, R.I., McLeod, C.J. (2005) RNA-mediated neurodegeneration caused by
the fragile X premutation rCGG repeats in Drosophila. CHEMTRACTS - Biochemistry
and Molecular Biology 18:153-8
Dudding, T.E., Friend, K., Schofield, P.W., Lee, S., Wilkinson, I.A., Richards,
R.I. (2004) Autosomal dominant congenital non-progressive ataxia overlaps with
the SCA15 locus. Neurology 63: 2288-92
La Spada A.R., Richards, R.I., Wieringa, B. (2004) Dynamic mutations on the
move in Banff. Nature Genetics 36: 667-70
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