Mihail Iordanov

Ph.D., Fridericiana University of Karlsruhe (Germany), 1995

Research Assistant Professor, Cell and Developmental Biology

The question of whether an individual cell lives or dies is of paramount importance not only for the cell itself, but also for the multicellular organism that harbors it. Our research is oriented towards the understanding of the mechanisms of cell survival and programmed cell death (apoptosis) in specific cell types. For instance, one major project focuses on the signal transduction events that underlie the pro-survival and pro-apoptotic responses of human keratinocytes (the main cell type of the epidermis) to ultraviolet (UV) radiation, a relevant human skin carcinogen.
We apply a plethora of molecular and cellular approaches to investigate the involvement of signaling proteins (e.g. receptors for growth factors and cytokines, GTPases, kinases, phosphatases, and transcription factors) in mediating the decisions of keratinocytes to survive or to commit cell suicide following exposure to UV. One example of a particular signaling pathway we investigate is the UV-induced regulation of the Ras GTPases and their downstream effectors, the extracellular signal-regulated kinases ERK1 and ERK2. Another major project focuses on the roles played by the stress-activated protein kinases JNK1 and JNK2 in the protective responses to toxic electrophilic compounds that challenge the cellular antioxidant defenses and cause oxidative stress. These compounds are either environmental pollutants (e.g. arsenic) or drug metabolites produced inside cells by cellular drug-activating enzymes. Our research may lead to the development of novel strategies for counteracting the harmful impact of important environmental pollutants and human carcinogens.

Selected publications:

Iordanov, M., J. Wong, J. Bell, and B. Magun. 2001. The activation of NF-kB 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. Molecular and Cellular Biology 21 (1), 61-72.

Iordanov, M., O. Ryabibina, J. Wong, T.-H. Dinh, D. Newton, S. Rybak, and B. Magun. 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., J. Paranjape, A. Zhou, J. Wong, B. Williams, E. Meurs, R. Silverman, and B. Magun. 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. Molecular and Cellular Biology 20(2), 617-627.

Iordanov, M. and B. Magun. 1999. Different mechanisms of c-Jun NH2-terminal kinase-1 (JNK1) activation by ultraviolet-B (UV-B) radiation and by oxidative stressors. Journal of Biological Chemistry 274, 25801-25806.

Iordanov, M., D. Pribnow, J. Magun, T.-H. Dinh, J. Pearson, and B. Magun. 1998. Ultraviolet radiation triggers the ribotoxic stress response in mammalian cells. Journal of Biological Chemistry 273, 15804-15813.

To contact Dr. Iordanov directly: iordanov@ohsu.edu