My research interest is to study the molecular mechanism of human chromosomal diseases, including 9p deletion syndrome. The terminal deletion of the short arm of human chromosome 9 (9p-) is associated with trigonocephaly, severe mental retardation, and dysmorphic facial features. The gene(s) responsible for 9p- syndrome remain to be elucidated. Using database analysis, we have identified over 270 highly conserved non-coding sequences that are conserved between the human and mouse or between human and zebrafish. These sequences are located within the critical region for 9p- syndrome. Studies have shown that highly conserved non-coding sequences may contain regulatory elements, which enhance (enhancers) or suppress (repressors) gene expression. We have cloned and tested 15 sequences from these 270 sequences, and successfully identified several enhancers and repressors by using a dual luciferase assay.

The ultimate goal is to find regulatory sequences for the most likely candidate genes responsible for 9p- syndrome. Another on-going project in our laboratory is investigation of the expression activity of the human Cerberus 1 gene in mesenchymal progenitor cells and in human embryonic stem cells approved by NIH for research. Cerberus 1 (CER1) gene is a good candidate for causing trigonocephaly when it is deleted, as seen in 9p- patients. To investigate the function of CER1 during osteogenic differentiation, we treat the mesenchymal progenitor cells with supplements so that they will differentiate into osteogenic cells. Then, total RNA from untreated and treated mensenchymal progenitor cells is isolated and purified. We are now quantifying the gene expression activities of the CER1 gene and key osteogenic markers and establishing an expression profile for the CER1 gene.

The goal is to understand the function of the CER1 gene during osteogenic differentiation. These research projects have been carried out with the assistance of undergraduates. Gateway cloning, polymerase chain reaction (PCR), quantitative PCR, mammalian tissue culture, gene transfection, and dual luciferase assay are routinely used in our laboratory.