The broad research theme of this lab is to study the functioning and regulation of genes in eukaryotic cells. In particular, we are interested in the understanding of the functional roles of chromosome structure, epigenetic modifications, and factor interaction network in the expression of genes during cell differentiation and development.
Several experimental systems are used in the lab. One is the mammalian globin gene switch. In particular, we are identifying the key(s) to turn on-and off the different globin gene members during erythroid development. We are studying the regulation of the subcellular locations of the erythroid-specific factor EKLF and its role in transcriptional activation and repression. thus providing new therapeutic agents for the cure of hemoglobinopathies including sickle cell anemia and severe β-thalassemias.
Another system is the DNA and histone methylation programs in eukaryotic cells including the mammals and Drosophila. Among our studies, we pioneered the demonstration of the existence of a DNA methylation program in Drosophila, and the regulatory roles of two histone methyltransferases in the expression of genes and transpasons on Drosophila chromosome 4. Most recently, we have discovered that the vertebrate DNA methyltransferases also could act as DNA dehydroxymethylases and demethylases in vitro. The possible significance of this finding in vivo is being explored.
Finally, we have been studying the neuronal functions of the RNA-binding protein, TDP-43, which is a patheo-signature protein of two major classes of neurodegenerative diseases, the frontal temporal-lobar-dementia (FTLD)-TDP and amyotrophic lateral sclerosis (ALS)-TDP. Thus, we are heading towards understanding the molecular and cellular basis of dysregulation of learning/memory and motor function in specific neurodegenerative diseases and developing effective therapeutic reagents for these diseases.