The storage and control center of a cell’s genetic information is its nucleus, where instructions for building and maintaining an organism are organized, sent, and received. Between 2,000 to 4,000 small channels or pores in the nuclear membrane provide the main gateway between the outside (the cytoplasm) and inside of the nucleus, allowing passage of proteins and messenger RNA (mRNA). Relative to other protein structures in the cell, the nuclear pore complex (NPC) is immense, making study of its function and activity challenging.
Using chemical biology, genetics in yeast and C. elegans roundworms, and other models, the Hanover lab studies enzymes and molecular pathways that control how important proteins find their way to the nucleus, how they interact with the NPC, and how material is imported and exported. We identified a new nuclear transport pathway that plays a role in determining the sex of mammals and in how stem cells become more specialized.
The lab also researches a specific enzyme called O-linked GlcNAc transferase (OGT) that modifies the NPC. Although this enzyme is found in a number of tissues in the body, it is most highly expressed in human pancreas cells that produce insulin. We think that activity of this OGT protein is the final step in a pathway that becomes impaired in diabetes mellitus (NIDDM).