Palmitoyl acyltransferase, Zdhhc13, facilitates bone mass acquisition by regulating postnatal epiphyseal development and endochondral ossification: a mouse model.

Our overall research interests are in translational research. We aim at translating the promise of genomic medicine into clinical reality.

Specific projects at present time include:

1). Identification of novel genes/targets associated with human diseases. This includes susceptibility genes for common multi-factorial diseases and adverse drug reactions. Genetic epidemiology, mouse ENU mutagenesis, bioinformatics and proteomics are some approaches that we use in identification of novel genes associated with the human disease. Genetic markers associated with drug-induced Stevens-Johnson syndrome and other adverse drug reactions have been identified. Prospective studies are in progress to assess the utilization of these markers to prevent the adverse drug reactions. A systematic, genome-wide, phenotype-driven mutagenesis program for gene function studies in the mouse have resulted in the identification of several mouse models of human genetic metabolic diseases. We will continue our research along these lines to identify more novel disease genes/ targets and to increase our understanding of the diseases.

2). Genetics and molecular mechanisms of Stevens-Johnson syndrome. With the identification of HLA-B allele strongly linked to the genetic susceptibility to the drug-induced Stevens-Johnson syndrome, we are investigating how the specific HLA allele mediated the cell toxicity in causing disseminated keratinocyte death.

3). Functional characterization of a novel glucose transporter and its role in diabetes mellitus. We cloned a novel glucose transporter (Glu 10), which is highly expressed in pancreas and liver and is located on a region of a chromosome where a diabetes mellitus type II locus has been mapped. We are currently investigating its role in diabetes by studying mouse models carrying the GLU10 mutations and by direct genetic association study of human patients affected with diabetes.

4). Enzyme and gene therapy and targeting mechanisms of Pompe disease.
Pompe disease is a fatal genetic muscle disorder. As enzyme replacement therapy for Pompe disease moves into clinical reality the fundamental question of how the enzyme targets the heart and skeletal muscle and why some patients respond better than others remain unanswered. We have generated tissue-specific MPR300 knockout mouse model and other animal models to help answer these questions.