Bruce Magun
Ph.D., Tufts University, Massachusetts, 1969
Professor and Chairman, Cell and Developmental Biology
My laboratory studies molecular mechanisms used by cells to communicate signals generated by growth factors, environmental stressors, and viruses. My research program is supported by grants from the National Cancer Institute and the National Institute for Environmental Health Sciences. Some projects are focused on understanding the different cellular signaling pathways used by cancer cells, and on distinguishing ways that these cells differ from normal cells. Other projects are aimed at understanding how cells exposed to environmental stressors such as ultraviolet radiation, toxic substances, and viruses are induced to undergo programmed cell death (apoptosis). The decisions that cells make to live or die depend on the balance of pro- and apoptotic signals that are generated in response to cellular stressors. Many of these signals are conveyed via activation of the stress-activated protein kinases (SAPKs) and through activation of the kinases that modulate the transcription factor NF-kB. Activation of these latter pathways leads to the induction of genes that are essential in regulating the responses of cells to stresses. The survival pathways activated in damaged cells are thought to be involved in tumor promotion and progression.
My laboratory has demonstrated that the ribosomes are organelles intimately involved in sensing cellular damage and communicating signals to stress-activated protein kinases. Recently we have identified novel signaling pathways by which viruses, through the production of double-stranded RNA, induce the activation of NF-kB, the SAPKs, and control the apoptosis of infected cells. Using gene microarrays, we have identified families of genes whose expression is induced in response to viral infection. In another line of investigation, we have explored the ways that onconase, a novel cancer chemotherapeutic, activates the SAPKs and leads to the rapid apoptosis of cancer cells.
Iordanov, M., Ryabinina, O., Wong, J., Dinh, T.-H., Newton, D., Rybak,, S. and Magun, B.E.(2000) Molecular determinants of apoptosis induced by the cytotoxic ribonuclease onconase: evidence for cytotoxic mechanisms different from inhibition of protein synthesis. Cancer Research 60:1983-1994.
Iordanov, M.S., Paranjape, J.M., Zhou, A., Wong, J., Williams, B.R.G., Meurs, E.F., Silverman, R.H., and Magun, B.E. (2000) Activation of p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase by double-stranded RNA and encephalomyocarditis virus: involvement of Rnase L, protein kinase R, and alternative pathways. Mol. Cell. Biol. 20:617-627.
Iordanov, M., Wong, J., Bell, J.C., and Magun, B.E. (2001). The activation of NFkB by double-stranded RNA (dsRNA) in the absence of protein kinase R and RNase L demonstrates the existence of two separate dsRNA-triggered anti-viral programs. Mol. Cell. Biol.21:61-72.
To contact Dr. Magun directly: magunb@ohsu.edu