Faculty Profile: Rebecca Page, PhD

Rebecca Page
Rebecca Page, PhD
Associate Professor of Biology
Molecular Biology, Cell Biology, & Biochemistry
My laboratory uses X-ray crystallography , NMR spectroscopy and small angle X-ray scattering (SAXS) in combination with biochemistry and genetics to understand the molecular basis of protein function, with a particular interest in understanding how bacterial signaling proteins regulate biolfim formation and antibiotic resistance, how targeting proteins direct the activity of ser/thr phosphatases and how dual specificity and tyrosine phosphatases regulate MAPK function.

Biography

Professor Page received dual B.S. degrees with honors in Biochemistry and Applied Mathematics from the University of Arizona in 1993 and completed her graduate work in Chemistry with Dr. C. E. Schutt as an NSF graduate and Harold W. Dodds fellow at Princeton University (PhD, 2000). From 2000 - 2003, she was a NIH NRSA post-doctoral fellow at The Scripps Research Institute with Dr. Ray Stevens, after which she joined the Joint Center for Structural Genomics with Dr. Ian Wilson to become the core leader of high-throughput crystallization group. In 2005, she joined the Molecular Biology, Cell Biology and Biochemistry department at Brown University as an assistant professor. The focus of her research is to elucidate the structures and dynamics of the transient macromolecular complexes that drive signaling in eukaryotic and prokaryotic cells.

Institutions

Princeton University

Research Description

Biofilms, persistence and antibiotic resistance
Bacterial biofilms are complex communities of cells containing an increased prevalence of dormant cells known as persisters, which underlie the multidrug tolerance of biofilms. However, a detailed understanding of how they assemble and how they are regulated at a molecular level is still only rudimentarily understood. Using a combination of structural, genetic and biochemical studies, we discovered that the E. coli protein mqsR, which is the most highly upregulated gene in persister cells, together with mqsA, are the defining members of an entirely new family of toxin:antitoxin systems which are essential for persistence. We are now invesitgating how the MqsA:MqsR TA system regulates biofilm formation and antibiotic resistance in vivo and new chemical tools to inhibit mqsRA mediated persistence in the cell.

PP1 holoenzymes in the nucleus
The regulation of the Ser/Thr phosphatase protein phosphatase 1 (PP1) is controlled by a diverse array of regulatory proteins. However, how these proteins direct the specificity of PP1 is not well understood. In addition, while 100's of cell biology and biochemical reports describe key biological roles for PP1, very few structural efforts have so far been successful. We are focusing on two PP1-targeting proteins-- the nuclear ihibitor of PP1 (NIPP1) and the PP1 nuclear targeting subunit (PNUTS)--to elucidate, at a molecular level, the biological functions and modes of action of these key nuclear PP1 holoenzymes in order to provide unique novel insights into the molecular regulation of PP1.

Regulation of MAPKs by phosphatases
MAP kinases transduce environmental and developmental signals into adaptive and programmed responses. In the cell, MAPK are regulated by numerous phosphatases. For example, the hematopoietic tyrosine phosphatase (HePTP) negatively regulates T cell activation in lymphocytes via ERK2 dephosphorylation. However, only very limited structural information is available for these biologically important complexes. We are combining X-ray crystallography, NMR spectroscopy, SAXS to characterize the structures of the MAPK:PTP complexes and ITC to understand the energetics of binding.

Grants and Awards


  • 2010-2015 NSF-CAREER award
  • 2013 18th Annual Gehrenbeck Lecturer
  • 2013, Session Chair, ACA Annual Meeting
  • 2008-2011 American Cancer Society Research Scholar
  • 2008 Hazeltine Citation Nominee, Brown University
  • 2008 Session Chair, IUCR Congress
  • 2005 Rhode Island Foundation Medical Research Grant
  • 2005 Richard B. Salomon Faculty Research Award
  • 2000-2003 NIH Ruth L. Kirschstein NRSA
  • 1997-1998 Harold W. Dodds Honorific Graduate Fellowship
  • 1994-1997 National Science Foundation Graduate Fellowship
  • 1993-1994 Phi Beta Kappa
  • 1992-1993 Barry M. Goldwater Undergraduate Research Scholar
  • 1988-1992 Regent's Academic Achievement Scholarship

Affiliations


  • 2012 - 2017 Editorial Board Member, Journal of Biological Chemistry
  • 2005–present Associate Editor, Protein Expression and Purification
  • 2004-present American Crystallographic Association
  • 2007-2010 Executive Board Member, PERG-ABRF/FASEB

    Funded Research


    • 2011-2016 National Institute of Health, NIGMS R01GM098482
    • 2010-2015 National Science Foundation, NSF-CAREER MCB0952550
    • 2012-present Johnson & Johnson, COSAT award
    • 2008-2011 American Cancer Society, RSG-08-067-01-LIB
    • 2010 Brown University, Seed Award
    • 2008-present Schering-Plough/MERCK
    • 2006 Brown University, Seed Award

Selected Publications