Rita Shiang, Ph.D.

• Associate Professor of Human Genetics
• Member Scientist, VCU Philips Institute

Office Location: Sanger Hall, Room 11-059
P.O. Box: 980033
Phone: (804) 828-9632 ext 124
Fax: (804) 828-3760
E-mail: rshiang@vcu.edu

Research Interests

The focus in the laboratory is to identify and characterize genes that cause human genetic disease. The diseases studied in the laboratory include the craniofacial disorder, Treacher Collins syndrome and Wolfram Syndrome, a heterogeneous neurodegenerative disorder whose main symptoms include diabetes insipidus, diabetes mellitus, optic atrophy and deafness. These disorders have been localized to human chromosomes 5 and 4q.

We identified the gene that causes Wolfram Syndrome 2. The gene, ZCD2, encodes a highly conserved novel protein, ERIS, which is localized to the endoplasmic reticulum. Studies of the Wolfram Syndrome 1 gene indicates that abnormal cellular calcium concentrations may play a role in this disorder. It is well known that the endoplasmic reticulum stores calcium in a cell. Cells from affected individuals with Wolfram syndrome 2 did not show differences in resting intracellular calcium concentrations when compared to controls but when stimulated, affected cells had significantly higher calcium influx than control cells. Thus, cellular and endoplasmic reticulum calcium concentrations may also be important in Wolfram Syndrome 2. These studies are ongoing. Future studies include the creation of a mouse model of Wolfram syndrome to study the disorder in vivo.

A large focus of the laboratory is the characterization of the Treacher Collins syndrome gene, Tcof1. The protein treacle has homology to a family of nucleolar phosphoproteins. Studies have shown that treacle is involved in rRNA transcription and processing which impacts cell proliferation and apoptosis. Microarray analysis of cell lines with the expression of the Tcof1 gene manipulated has identified a number of genes that are coordinately and oppositely expressed with Tcof1 which have given us insights into downstream targets of treacle. To study the importance of these gene expression changes we will use in vitro analysis of cell lines and in vivo analysis using a conditional knockout mouse model and a zebrafish Tcof1 knockdown model in collaboration with Dr. James Lister. These models will also be valuable in testing possible treatments for Treacher Collins syndrome.

Honors

• 2003: Faculty Research Achievement Award for the Department of Human and Molecular Genetics, School of Medicine, VCU
• 2003: Outstanding Teacher Award for the Department of Human and Molecular Genetics, School of Medicine, VCU
• 1996-1998: Arthritis Investigator Award
• 1989: Young Investigator Travel Award from the 10th International Workshop on Human Gene Mapping, New Haven, Conn.
• 1985-1990: National Institutes of Health Predoctoral Trainee - Grant GM 5 T32 07091-15

Funded Research

• J-859: Characterization of Genes Downstream of the Treacher Collins Syndrome Gene, Tcof1, Jeffress Memorial Trust

Selected Publications

1. Amr, S., Heisey, C., Zhang, M., Xia, X.-J., Shows, K.H., Ajlouni, K., Pandya, A., Satin, L.S., El-Shanti, H., Shiang, R. (2007). A Homozygous Mutation in a Novel Zinc Finger Protein, ERIS, is Responsible for Wolfram Syndrome 2. Am J Hum Genet 81:673-683, Epub 2007 August 20.
2. Shows, K.H., Ward, C., Summers, L., Li, L., Ziegler, G.R., Hendrickx A.G., *Shiang, R.* (2006). Mutation Analysis of /TCOF1/ in a rhesus macaque with Treacher Collins syndrome. /Mammalian Genome/ *17*:2:168-77, Epub 2006 Feb 7.
3. Rees, M.I., Harvey, K., Pearce, B.R., Chung, S.K., Duguid, I.C., Thomas, P., Beatty, S., Graham, G.E., Armstrong, L., *Shiang, R.*, Abbott, K.J., Zuberi, S.M., Stephenson, J.B., Owen, M.J., Tijssen, M.A., van den Maagdenberg, A.M., Smart, T.G., Supplisson, S., Harvey, R.J. (2006). Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease. /Nat Genet/ *38*:7:801-806, Epub 2006 June 4.