TAO WANG, M.D., Ph.D. 
Tao Wang, MD, PhD
Assistant Professor of Pediatrics and Institute of Genetic Medicine
Research interests:
- Molecular basis of X-linked mental retardation and human cognitive development.
- Pathogenesis and therapy of inherited metabolic diseases with CNS involvement
Main Interests:
Mental retardation is the most common cause of severe handicaps in children and young adults affecting 2-3% of general population. X-linked mental retardation (XLMR) occurs in 1 in 600 males and is genetically heterogeneous with 150-200 responsible loci on the X chromosome. Less than 40 XLMR genes were cloned until recently. Current research efforts in our laboratory focus on delineation of the molecular basis of XLMR using molecular biology and genomic approaches. Specifically, we have developed a strategy of using a human X chromosome-specific cDNA microarray to identify genes with mutations that result in a change in the abundance of mRNA due to mechanism such as promoter mutations, gene deletions or duplications, nonsense or frame-shift mutations associated with nonsense mediated mRNA decay. This method has the advantage of quantitative analysis of gene expression in multiple samples and is not limited by the requirement for large pedigrees. It would be particularly useful for the identification of primary genetic defects in rare, heterogeneous X-linked conditions, and modifier genes on the X chromosome that contribute to common diseases. A preliminary survey of lymphoblast cell lines from 32 XLMR probands using ths approach identified several candidate genes with significant reduction in the abundance of their mRNA. mRNA reduction in XLMR probands was independently confirmed by Northern blot and/or real time PCR. Molecular characterization of these candidate genes, functional studies using both in vitro and in vivo methods, and clinical studies of XLMR patients are being carried out.
Selected publications
- Wang T, Lawler AM, Steel G, Milam AH, and Valle D (1995) Mice lacking ornithine-d-aminotransferase have paradoxical neonatal hypoornithinemia and retinal degeneration. Nature Genet 11:185.
- Wang T, Milam AH, Steel G, and Valle D (1996) Mouse model of gyrate atrophy of choroid and retina: evidence for early retinal pigment epithelium damage and progressive retinal degeneration. J Clin Invest 97: 2753.
- Wang T, Milam AH, Steel G, and Valle D (2000) Correction of ornithine accumulation prevents retinal degeneration in a mouse model of gyrate atrophy of the choroid and retina. Proc Natl Acad Sci USA 97:1224.
- Wang T, Steel G and Valle D (2001) Oral lysine supplementation reduces plasma ornithine in a mouse model of gyrate atrophy of the choroid and retina (GA). Am J Hum Genet 69:201
- Wang T, Zhang L, Obie C, Mousses S, Trent J, and Valle D (2002) Identification of genes responsible for X-linked mental retardation using a human X chromosome-specific cDNA microarray. Am J Hum Genet. (submitted).
