Dr. Che-Kun James Shen ¨H­õó˳դh

Distinguished Research Fellow, IMB

Research

Eukaryotic Gene Regulation and Development

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. Eventually this will enable us to re-turn on embryonic/fetal globin genes in adult cells, thus providing new therapeutic strategies for the cure of hemoglobinopathies including sickle cell anemia and severe thalassemias. Presently, we are focusing on the regulation of the subcellular locations of two erythroid gene transcription factors, p45/ NF-E2 and EKLF, by protein modifications and factor-factor interaction.

Another system is the DNA and histone methylation programs in eukaryotic cells including the mammals and Drosophila. Among our studies, we pioneered the demonstration the existence of a DNA methylation program in Drosophila and the identification of the candidate gene dDNMT2 responsible for the fly genome methylation life span regulation. Currently, we are identifying novel gene regulation pathways involving epigenetic factors including the methylated DNA- binding proteins and histone methyltransferases, in both flies and mammals.

Finally, we have been studying the neuronal/brain function with respect to the roles of fast-evolving brain genes and RNA-binding proteins in learning/ memory-related RNA granule transport and protein translation in neurites. Extending this, we also head towards understanding the dysfunction of learning/ memory in specific neurodegenerative diseases.