Boston University Department of Biology

Faculty Profiles

Current Research

Our laboratory studies the roles of proto-oncogene proteins in the signal transduction pathways that control proliferation and survival of mammalian cells. Current researvh is focused on the mechanisms by which the phosphatidylinositol 3-kinase (PI 3-kinase)/Akt signaling pathway regulates cell survival by suppressing apoptosis. The targets of PI 3-kinase/Akt signaling include the Bcl-2 family member Bad, a variety of transcription factors, and the protein kinase GSK-3. Substrates of GSK-3 also include a variety of transcription factors, as well as the translation initiation factor eIF2B. It thus appears that PI 3-kinase/Akt/GSK3 signaling regulates gene expression at both the levels of transcription and translation. At the translational level, we have found that inhibition of translation resulting from phosphorylation of eIF2B plays an important role in apoptosis, at least in part due to turnover of the Bcl-2 family protein Mcl-1, whose rapid degradation couples global translational regulation to cell survival.

Our studies of transcriptional regulation have used global gene expression profiling to identify genes that are regulated by PI 3-kinase/Akt/GSK-3 signaling. We have combined these results with computational prediction of transcription factor binding sites to identify transcription factors that are targeted by the PI 3-kinase/Akt/GSK3 pathway. These computational predictions coupled with experimental verification have identified FOXO, NFkB, and CREB as key targets of PI 3-kinase signaling. We are extending these studies with the goal of elucidating the transcriptional regulatory network that coordinates PI 3-kinase-regulated gene expression in mammalian cells.

Courses Taught

• BI 203 Cell Biology
• BI 213 Honors Cell Biology

Selected Publications

• Saxena UH, Powell CMH, Fecko JK, Cacioppo R, Chou HS, Cooper GM, Hansen U. (2009). Phosphorylation by cyclin C/CDK2 following mitogenic stimulation of murine fibroblasts inhibits transcriptional activity of LSF during G1 progression. Molecular and Cellular Biology 29, 2335-2345.
• Terragni J, Graham, JR, Adams KW, Schaffer MW, Tullai JW, Cooper GM. (2008). Phosphatidylinositol 3-kinase signaling in proliferating cells maintains an anti-apoptotic transcriptional program mediated by inhibition of FOXO and non-canonical activation of NFkB transcription factors. BMC Cell Biol. 9, 6.
• Tullai JW, Schaffer ME, Mullenbrock S, Sholder G, Kasif S, Cooper GM. (2007). Immediate-early and delayed primary response genes are distinct in function and genomic architecture. J. Biol. Chem. 282, 23981-23995.
• Adams KW, Cooper GM. (2007). Rapid turnover of Mcl-1 couples translation to cell survival and apoptosis. J. Biol. Chem. 282, 6192-6200.
• Tullai JW, Chen J, Schaffer ME, Kamenetsky E, Kasif S, Cooper GM. (2007). GSK-3. mediates repression of CREB target genes in quiescent cells. J. Biol. Chem. 282, 9482-9491.
• Pap M, Cooper GM. (1998). Role of glycogen synthase kinase-3 in the phosphatidylinositol 3-kinase/Akt cell survival pathway. J. Biol. Chem. 273, 19929-19932.
• Dudek H, Datta SR, Franke TF, Birnbaum MJ, Yao R, Cooper GM, Segal RA, Kaplan DR, Greenberg ME. (1997). Regulation of neuronal survival by the Ser/Thr protein kinase Akt. Science 275, 661-665.
• Yao R, Cooper GM. (1995). Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by nerve growth factor. Science 267, 2003-2006.