Areas of Interest
To understand the molecular basis of growth regulation, this laboratory studies mechanisms for regulation of gene expression by growth factors. Major goals are to identify signal transduction pathways between growth factor receptors and target genes in the nucleus, and to identify mechanisms by which growth factors regulate trascription factor function.
One of our key approaches is to focus on the actions of growth hormone, a critical regulator of normal growth, and related factors which also signal by receptors in the cytokine receptor superfamily, including interferons and interleukins. By examining how growth hormone activates the proto-oncogene c-fos, we have identified three different signaling pathways that culminate on different transcription factors associated with the c-fos promoter: The Jak-STAT pathway mediates activation of STAT transcription factors by tyrosine phosphorylation, the Ras-MAP kinase pathway culminates in an activating serine phosphorylation of the transcription factor Elk-1, and a potentially inhibitory pathway regulates the transcription factors C/EBP beta and delta, which have been implicated in cell differentiation and proliferation. Current work examines cross-talk among the multiple signaling pathways and potential interactions among the transcription factors regulated by growth hormone. To assess molecular mechanisms by which growth factors promote differentiation of target cells (e.g. adipocytes), we are also examining effects of growth factors and cytokines on the function of genes associated with cell differentiation and cell cycle regulation. Ultimately, our studies will provide insight into how regulation of early gene expression contributes to changes in cell growth, differentiation and metabolism, and will be important for an understanding of diseases such as cancer and diabetes.
SELECTED PUBLICATIONS: Liao J, Piwien-Pilipuk G, Ross S, Hodge C, Sealy L, MacDougald O, Schwartz J. "C/EBP Beta and Delta Contribute to Growth Hormone Regulated Transcription of C-Fos." J Biol Chem., 274: 31597-31604, 1999.
Piwien-Pilipuk G, van Mater D, Ross SE, MacDougald OA, Schwartz J. "Growth Hormone Regulates Phosphorylation and Function of C/EBPb by Modulating Akt and Glycogen Synthase Kinase-3." J. Biol. Chem., 276:19664-19671, 2001.
Piwien-Pilipuk G, MacDougald OA, Schwartz J. "Dual Regulation of Phosphorylation and Dephosphorylation of C/EBPb Modulate its Transcriptional Activation and DNA Binding in Response to Growth Hormone." J Biol Chem., 277: 44557-44565, 2002.
Piwien-Pilipuk G, Huo JS, Schwartz J. "Growth Hormone Signal Transduction." J. Pediatric Endocrinol. Metab., 15: 771-786, 2002
Bennett CN*, Hodge CL*, MacDougald OA, Schwartz J. "Roles of Wnt10b and C/EBP Alpha in Spontaneous Adipogenesis of 243 Cells." Biochem Biophys Res Communic, 302:12-16, 2003. (* contributed equally)
Piwien Pilipuk G, Galigniana MD, Schwartz J. "Subnuclear Localization of C/EBP Beta is Regulated by Growth Hormone and Dependent on MAPK." J. Biol. Chem., 278: 35668-35677, 2003.
Ph.D., Harvard, 1974