Gerard Ostheimer

Education

A.B. Dartmouth College,1990

M.S, Montana State University, 1992

Ph.D., University of Oregon, 2003

CDP Research

I am interested in how cells process information to generate a change in cell state. Examples of such changes include development, migration, proliferation and apoptosis. I study how cancer cells respond to the traditional cancer therapies of ionizing radiation and chemotherapy. These traditional therapies kill cells by inducing DNA damage that in turn leads cells to apoptose. In these instances the DNA damage acts as an input to a signaling network that initially results in cell cycle arrest followed by either repair of the damage and re-entry into the cell cycle or activation of the apoptotic machinery. I am using a data-driven modeling approach to understand in a quantitative way how cells compute whether to survive or to apoptose. A key aspect of my work is the belief that it is necessary to correlate signaling events with cellular outcomes. Co-workers and I monitor the signaling response of cells to ionizing radiation of chemotherapy as well as the cellular outcomes that result. We monitor the dynamic signaling activities of proteins in the DNA damage response (e.g. p53, Chk1, Chk2, etc.), the stress and mitogen activated protein kinases (e.g. Erk, Akt, etc.), the cell cycle machinery (e.g. cyclin levels) and the apoptotic machinery (e.g. Bcl-2 family member protein levels) and correlate these signaling measurements to cellular outcome measurements the cell cycle, apoptosis and proliferation using partial least squares regression. Partial least squares regression (PLSR) is an unsupervised method for discovering correlations between data sets. PLSR extracts from the signaling vectors that correspond to different cellular outcomes (i.e. survival or apoptosis). In this way we hope to identify the signaling dynamics that underlie these opposite cellular outcomes.

Publications

Linding, R., Jensen, L.J., Ostheimer, G.J., van Vugt, M.A., Jørgensen, C., Miron, I.M., Diella, F., Colwill, K., Taylor, L., Elder, K., Metalnikov, P., Nguyen, V., Pasculescu, A., Jin, J., Park, J.G., Samson, L.D., Woodgett, J.R., Russell, R.B., Bork, P., Yaffe, M.B., and Pawson, T. (2007) Systematic discovery of in vivo phosphorylation networks. Cell 129, 1415-26.