Richard B. Jones, Ph.D.

Focused Systems-Level Analyses of Cellular Signal Transduction

Research Summary

In order for living creatures to progress from single cells to multi-cellular tissues, organs, and ultimately to whole organisms, they must utilize complex autocrine, paracrine, and endocrine communication mechanisms that we are only beginning to understand at the molecular level.  While large scale analyses of cellular, tissue-level, and whole organism gene expression patterns have been performed in a scalable, systematic, and high-throughput manner with the DNA microarray and other platforms, the analysis of dynamic protein signaling networks has proven a much greater technological challenge.  At one extreme, cell biologists have examined total protein abundance and post-translational modification state from whole cells and tissues while at the other extreme biochemists and biophysicists have studied how a single post-translational modification can give rise to a change in protein structure and function.  The focus of our laboratory lies at the interface between these extremes and is the result of the belief that the use of technological approaches at the interface of scientific disciplines and scales will result in paradigm-shifting systems-level insights into fundamental biological processes and will simultaneously result in the development of tools with wide ranging applicability to cancer and other clinically relevant biology. 

Toward this end, we are utilizing protein micro-array, mass spectrometric, and cell biological tools to query both the theoretical biophysical nature of protein-protein interaction connectivity as well as the dynamics of cellular protein abundance, post-translational modification, and interaction connectivity.  We are focusing our efforts primarily on those interactions and modifications that would not be easily addressed using traditional yeast two hybrid methodologies.  Our goal is to gain a better understanding of the modular signaling molecules whose location, abundance, and modification state underlie cell growth, migration, differentiation, and cell death: These processes lie at the heart of cancer biology and an understanding of these processes at the molecular level should enable the identification of many new therapeutic targets. 

We are very interested in receiving applications from motivated students and postdoctoral researchers who wish to work at the interface of Biology, Chemistry, Physics, and Mathematics to better understand the signal transduction mechanisms that result in cancer, diabetes, and other human disease.

Selected Papers

Hause, R.J., Kim, H.D., Leung, K., Jones R.B. (2011) Targeted protein-omic methods are bridging the gap between proteomics and hypothesis-driven protein analysis approaches. Expert Opinion in proteomics.

Chevrier,N., Mertins,P, Artyomov, M.N., Shalek, A.K., Garber, M., Iannacone, M., Ciaccio, M.F., Gat-Viks, I., Eisenhaure, T.M., Clauser, K.R., Yosef, N., Tonti, E., Robinson, J., Sutton, A., Andersen, M.S., Root, D.E., von Andrian, U., Jones, R.B., Park, H., Carr, S.A., Regev, A., Amit, I., Hacohen, H. (2011) Systematic discovery of signaling components identifies new branches in viral-sensing pathways. Cell.

Wojcik, J., Hantschel, O., Grebien, F., Kaupe, I., Bennett, K.L., Barkinge, J., Jones, R.B., Koide, A., Superti-Furga, G., Koide, S. (2010) A potent and highly specific FN3 monobody inhibitor of the Abl SH2 domain. Nature Structural & Molecular Biology. doi:10.1038/nsmb.1793

Ciaccio, M.F., Wagner, J.P., Chuu, C-P., Lauffenburger, D.A., Jones, R.B. (2010) Systems analysis of EGF receptor signaling dynamics with microwestern arrays. Nature Methods. 7, 148 - 155

Netzer, N., Goodenbour, J.M., David, A., Dittmar, K.A., Jones, R.B., Schneider, J.R., Boone, D., Eves, E.M., Rosner, M.R., Gibbs, J.S., Embry, A., Dolan, B., Das, S., Hickman, H.D., Berglund, P., Bennink, J.R., Yewdell, J.W., Pan, T. (2009) Innate immune and chemically triggered oxidative stress modifies translational fidelity. Nature. 462, 522-526

Jones R. B., Gordus, A.G., Krall, J., MacBeath, G. (2006) A Quantitative Protein Interaction Network for the ErbB Receptors Using Protein Microarrays. Nature. 439(7073):168-74.