Sheldon S. Shen

Professor

Dr. Shen, Professor, received his B.S. (with honors) in Physics from the University of Missouri-Columbia and his Ph.D. in Physiology (NIH predoctoral trainee) from the University of California-Berkeley. He was NIH and NCI postdoctoral fellow in Zoology at UC-Berkeley. After serving as an Assistant Research Zoologist at UC-Berkeley, Dr. Shen joined the faculty at Iowa State University in 1979 as an Assistant Professor, and was promoted to Professor in 1989. His research interest has been ionic regulation of cellular activities with particular emphasis on calcium signaling during fertilization and membrane resealing.

Research Description

My research interest has been ionic regulation of cellular activities with particular emphasis on calcium signaling during fertilization and membrane resealing. Fertilization in all organisms studied to date triggers a necessary transient rise in calcium level in the egg. We initially demonstrated the sea urchin egg contains at least four sources for the transient rise in calcium during fertilization. Subsequent efforts have shown that production of inositol trisphosphate is necessary for most organisms, including mammalian egg activation by sperm, and is sufficient for development in sea urchins. We have recently isolated and characterized an isoform of phospholipase C-beta from the sea urchin egg. Although this isoform is not necessary for the immediate rise in calcium during fertilization, the isoform helps to sustain the calcium transient. Our current interest is the possible localization of the isoform during fertilization and its role during early development, such as nuclear envelope breakdown and first cleavage.

A second more recent research interest is plasma membrane resealing after cell wounding. Membrane resealing in mammalian cells after injury depends on calcium-dependent fusion of intracellular vesicles with the plasma membrane. When cells are wounded twice, the subsequent resealing is generally faster. Physiological and biochemical studies have shown the initiation of two different repair signaling pathways, which are termed facilitated and potentiated responses. The facilitated response is characterized by a faster resealing response to a second wound at the same initial wound site, and depends on the generation and recruitment of new vesicles in a protein kinase C and Golgi-dependent manner. Cells also have a globally increased exocytotic response to a second wound. This potentiated response is characterized by a faster resealing response to a second wound at a site different from the initial wound and apparently does not depend on the generation of new vesicles. The faster response was due to increased exocytosis that was both cAMP and protein kinase A dependent. The molecular mechanism of these calcium-regulated exocytosis appears to be highly conserved. Neurotoxin inhibitors of synaptic transmission also can inhibit membrane resealing, which indicates similar vesicle fusion proteins mediate exocytosis that is required for resealing. We have recently reported on using recombinant peptides, the specific roles for synaptotagmin VII and VAMP2/3 proteins during cell membrane repair. The use of RNAi may further delineate the VAMP isoform for membrane resealing. Our studies of resealing reveal a high degree of similarity with the fusion mechanisms of neurosecretion and suggest that membrane repair will be an important adjunct to understanding the molecular events in vesicle fusion. Presently we are establishing a rat cardiac cell culture system to study plasma membrane resealing after mechanical and laser-induced cell injury.

Contact Information:

511 Science Hall II

Ames, IA 50011-3221

515-294-8435 voice

515-294-8457 fax

Education:

B.S., University of Missouri, Columbia, 1969

Ph.D., University of California, Berkeley, 1974

• Shen, S.S. & R.A. Steinhardt. 2005. The mechanisms of cell membrane resealing in rabbit corneal epithelial cells.. Current Eye Research 30: 543-554.
• Kulisz, A., Dowal, L., Scarlata, S. & S.S. Shen. 2005. Cloning and characterization of a phospholipase C-beta isoform from the sea urchin Lytechinus pictus.. Development, Growth & Differentiation 47: 307-321.
• Shen, SS, Tucker, WC, Chapman, ER & RA Steinhardt. 2005. Molecular regulation of membrane resealing in 3T3 fibroblasts. Journal of Biological Chemistry 280: 1652-1660.
• Deng, M.Q. & S.S. Shen. 2000. A specific inhibitor of p34/cyclin B suppresses fertilization-induced calcium oscillations in mouse eggs.. Biology of Reproduction 62: 873-8.
• Kinsey, W.H. & S.S. Shen. 2000. Role of the Fyn kinase in calcium release during fertilization of the sea urchin egg. Developmental Biology 225: 253-264.