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Vanderbilt-Ingram Cancer CenterVanderbilt-Ingram Cancer Center

 
Susan R.  Wente

Susan R. Wente, Ph.D.

Provost
Vice Chancellor for Academic Affairs
Professor of Cell and Developmental Biology
Researcher

Contact Information:

Vanderbilt University
205 Kirkland Hall
Nashville, TN 37240
615-322-4219

Research Description

Our goal is to understand the mechanism for highly selective, bidirectional exchange of proteins and RNA between the nucleus and cytoplasm. Nucleocytoplasmic trafficking is essential for cell function, and precisely regulated during cell division, differentiation and death. At the center of the transport mechanism are the nuclear pore complexes (NPCs), large protein machines embedded in the nuclear envelope and the only known sites for nuclear entry and exit. We use yeast, cultured human cells, and zebrafish model systems to address three broad questions.

(1) How are NPCs assembled? At least 30 different proteins associate in a nuclear envelope pore to form an NPC. Using genetic strategies and GFP-tagged NPCs, we are identifying assembly factors and monitoring NPC dynamics in live cells.

(2) How do proteins and genetic material move through the NPC? By genetic, molecular and biochemical means, we are investigating the mechanism by which transport factors utilize NPC proteins for movement. Studies also focus on elucidating steps in mRNA export, coupling between mRNA export and translation, and roles for inositol polyphosphate signaling in regulating transport.

(3) How do mRNA export and mRNP processing factors regulate vertebrate development and disease? Using the zebrafish model system and mammalian cell culture, we have defined mechanisms of pathogenesis that open up entirely new areas of investigation.

These basic projects impact human disease in several ways. In higher eukaryotes, proper NPC assembly is required for cell division and for maintaining transport, particularly in rapidly dividing cells (e.g. cancer cells). Cancer cells can also alter gene expression by perturbing nuclear transport. During viral infections, nuclear transport factors and NPC protein functions are inhibited or exploited to mediate viral RNA export. Recently, we demonstrated that an embryonic lethal form of human motor neuron disease also results from disregulation of mRNA export. We predict that elucidation of the mechanisms for NPC assembly, translocation and regulation will uncover other pathogenic mechanisms and identify druggable targets for controlling human disease. Overall, our future work will continue to integrate our discoveries from the analysis of single cell machineries into the context of multicellular organism development and pathophysiology.

Publications