How we sense and react to our environment is communicated in the cell by vast networks of highly dynamic, interacting proteins. These interactions are regulated in both space and time, and it is this tight regulation that allows signals from outside of the cell to be rapidly and precisely transmitted to the nucleus leading to the appropriate, and healthy, cellular response. Her research integrates structural biology, biophysics and biochemistry in order to understand how these signals in both prokaryotes and eukaryotes are communicated in the cell at atomic resolution. During the last years, her group has focused on two problems: (1) how do toxin:antitoxin (TA) systems in bacteria lead to bacterial persistence and antibiotic resistance and (2) how are the activities of ser/thr phosphatases in the eukaryotic cell regulated. Our studies have made a transformative impacts in both fields. In microbiology and persistence, we: (1) discovered an entirely novel TA system (Type V; published in Nature Chemical Biology) and showed that a second TA system, MqsRA, defines a novel Type II subtype. In the second, a tour de force of crystallographic and functional studies led to the discovery of an entirely novel mechanism of substrate selection in ser/thr phosphatases: namely, that many PSP targeting and inhibitor proteins function to select substrates through a mechanism of steric inhibition. Furthermore, it also revealed the molecular basis by which the blockbuster immunosuppressants FK506 and cyclosporin A work—they bind and block one of the key calcineurin substrate binding grooves, demonstrating, for the first time, how these ubiquitous PSPs can be exploited for the development of highly specific drugs.
- Kumar, G.S., Ezgi, G., De Munter, S., Bollen, M., Vagnarelli, P., Peti, W. & Page, R. (2016) Molecular Assembly of the Ki-67:PP1 and RepoMan:PP1 Mitotic Phosphatases: Regulators of Chromatin Organization and Structure, Elife, 5:e16539.
- Wang, X., Bajaj, R., Bollen, M., Peti, W. & Page, R. (2016) Expanding the PP2A Interactome by Defining a B56-specific SLiM, Structure, 24(12):2174-2181.
- Sheftic, R.S., Page, R. & Peti, W. (2016) Investigating the human Calcineurin Interaction Network using the πɸLxVP SLiM, Nature Sci. Reports, 6:38920.
- Page, R., Peti, W. (2016) Toxin:antitoxins systems in bacterial growth arrest and persistence. Nature Chem Biol, 12: 208-214.
- Choy, M.S., Yusoff, P., Lee, I.C., Newton, J.C., Goh, C.W., Page, R., Shenolikar, S. & Peti, W. (2015) Structural and functional analysis of the GADD34:PP1 eIF2α phosphatase, Cell Reports, 11, 1885-1891
- Choy, M.S., Hieke, M., Kumar, G.S., Lewis, G.R. Gonzalez-DeWhitt, K.R., Kessler, R.P., Stein, B.J., Hessenberger, M., Nairn, A.C., Peti, W. & Page, R. (2014) Understanding Retinoblastoma Protein activation by PNUTS leads to the identification of the Protein Phosphatase 1 Regulatory Code, Proc Natl Acad Sci U S A, 111(11), 4097-4102.
- Grigoriu, S., Bond, R., Cossio, P., Chen, J.A., Ly, N., Hummer, Page, R., Cyert, M.S. & Peti, W. (2013) The molecular mechanism of substrate engagement and immunosuppressant inhibition of Calcineurin. PLoS Biology, 11(2), e1001492
- Wang, X., Lord, D.M., Cheng, H.-Y., Osbourn, D.O., Hong, S.H., Sanchez-Torres, V., Quiroga, C., Herrmann, T., Peti, W., Benedik, M.J., Page, R. & Wood, T.K. (2012) A new type V toxin-antitoxin system where mRNA for toxin GhoT is cleaved by antitoxin GhoS, Nat Chem Biol, 8, 855-861.
- Wang, W., Kim, Y., Ma, Q., Hong, S.H., Brown, B.L., Benedik, M.J., Peti, W., Page, R. & Wood, T.K. (2011) Antitoxin MqsA Helps Mediate the Bacterial General Stress Response, Nat Chem Biol, 7(6), 359-366.
1/2017 – present Associate Editor, Science Advances
2016-2021 NIH – MSFB, standing study section member
2016-2018 NSLS II scientific proposal, standing reviewer
2013 Eighteenth Annual Gehrenbeck Lecturer, Rhode Island College
7/2012 – present Editorial Board Member, Journal of Biological Chemistry
2010 – 2016 NSF-CAREER Award
2008 – 2011 American Cancer Society Research Scholar
2008 Hazeltine Citation Nominee (Brown University senior class teaching award)
2005 Brown University Richard B. Salomon Faculty Research Award
2000 – 2003 Ruth L Kirschstein National Research Service Award (NRSA), NIH
1997 – 1998 Harold W. Dodds Honorific Graduate Fellowship
1994 – 1997 National Science Foundation Graduate Fellowship
1992 Barry M. Goldwater Undergraduate Research Scholar