This is an application for a Mentored Clinical Scientist Development Award for Dr. Amy Simon to pursue research on the influence of reactive oxygen species (ROS) on the novel JAK/STAT transcription pathways of mammalian cells which are involved in cell signaling of most growth factors and cytokines. Her preliminary studies provide the first information that these pathways may also respond to oxidants and be involved in pulmonary injury such as that of respiratory distress syndrome or pulmonary fibrosis. Further exploration of these observations may provide new insights into understanding pathogenesis and therapy of these conditions. Dr. Simon will work in the laboratory of Dr. Brent Cochran (a recognized national leader in transcription factor regulation) at the Tufts University School of Medicine which is adjacent to the New England Medical Center and will have as a co-sponsor Dr. Barry Fanburg, who is an authority on oxidant injury to the lung. She will have available to her all facilities, courses and conferences of the Department of Cellular and Molecular Physiology as well as those which Dr. Fanburg organizes and will interact almost daily with Dr. Cochran and periodically with Dr. Fanburg and an Advisory Committee. Preliminary results from work already done by Dr. Simon show that oxidant stress activates the DNA-binding of transcription factors from the STAT family of proteins. Her continued research will focus on the following specific aims: 1) To define the different redox regulatory factors that mediate STAT activation, 2) To determine the mechanism of STAT activation by ROS, 3) To identify the elements in the c-fos promoter required for the response to ROS and 4) To identify other downstream target genes for this pathway. These studies should allow Dr. Simon to extend her research credentials and to be competitive for a future independent research award while she assumes a staff position at this institution.
| Simon, Amy R; Takahashi, Satoe; Severgnini, Mariano et al. (2002) Role of the JAK-STAT pathway in PDGF-stimulated proliferation of human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 282:L1296-304 |
| Simon, A R; Vikis, H G; Stewart, S et al. (2000) Regulation of STAT3 by direct binding to the Rac1 GTPase. Science 290:144-7 |
| Simon, A R; Rai, U; Fanburg, B L et al. (1998) Activation of the JAK-STAT pathway by reactive oxygen species. Am J Physiol 275:C1640-52 |
