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Barbara Imperiali, Ph.D.

Department of Chemistry
Class of 1922 Professor of Chemistry and Professor of Biology
MacVicar Faculty Fellow

Room 18-590
617-253-1838 (phone)
617-452-2419 (fax)


B.Sc. (Hon), University College London, London, England, 1979
Ph.D, Massachusetts Institute of Technology, Cambridge, MA, 1983
Carnegie Mellon University, Pittsburgh, PA, 1986-1989
California Institute of Technology, Pasadena, CA, 1989-1997
Ellen Swallow Richards Professor of Chemistry, MIT, Cambridge, MA, 1999
Class of 1922 Professor of Chemistry and Professor of Biology, MIT, Cambridge, MA, 2002

Research Summary

Research in the Imperiali group is concerned with diverse aspects of protein structure, function and design. One area of investigation focuses on co-translational protein glycosylation. A second program is targeted at the design and implementation of new chemical probes into the study of complex biological systems. In the protein glycosylation initiative Imperiali's group has made considerable progress towards understanding the functional and structural implications of asparagine-linked glycosylation. These studies have been carried out using an array of complementary chemical, physical and biological approaches. In the bioprobes arena, research on the use of oligopeptide motifs for metal ion sensing, and as minimal biophysical probes for structural and functional proteomics, has been pursued. Recently, the Imperiali group has joined efforts with groups pursuing initiatives that focus on the biological processes of cell migration and cell cycle control. The role of the Imperiali group in these multidisciplinary efforts is to develop new chemical tools to complement existing biological approaches for the analysis of these complex biological systems.

The main model system for developing and testing these bioprobes is the phenomenon of kinase-mediated phosphorylation and de-phosphorylation. Phosphorylation is one type of post-translational modification that produces major changes to the proteome. The development of probes that can measure the effects of phosphorylation in cells now enables studies of the mechanisms, timing and biochemical mediators involved in important biological processes.

Among the types of bioprobes that the Imperiali group have developed and applied are:

  • Fluorescent sensors for monitoring protein phosphorylation and dynamic protein interactions: Fluorescent markers are used to sense protein phosphorylation, to measure tyrosine kinase activity in cancer and to detect other kinases as markers of specific disease states. The Imperiali lab is developing high throughput methods to screen kinase activity levels in cells in vitro and in lysates prepared directly from healthy and diseased clinical samples. Additionally, the group has developed powerful environment sensitive fluorophores that can be integrates into proteins and report directly on dynamic interactions and conformational changes.
  • New species of caged phosphopeptides and phosphoproteins: Caged phosphoproteins and phosphopeptides are bioactive compounds whose functionality is masked by photolabile chemical moieties. The inert masked compounds can be introduced into living cells and then photolyzed to cleave off the masking group so that the biological function of the phosphoproteins can be measured inside cells in real-time. New methods for solid-phase peptide synthesis have been developed to assemble caged phosphorylated versions of serine, threonine and tyrosine. This approach can be used to introduce the products of protein phosphorylation into cells, in an inert form, so that their cellular roles can be measured directly upon uncaging with light energy. This methodology represents a powerful complement to existing genetic manipulations because it enables researchers to probe the roles of protein effectors in cell populations in real time.
  • Lanthanide binding tags (LBTs): Lanthanide binding expression tags are short peptide sequences (fewer than 20 amino acids) that are optimized to bind exogenous trivalent lanthanide (Ln3+) ions. Because these tags are built from encoded amino acids, they can be introduced into the DNA as coexpression tags to create fusion proteins. After the fusion protein is expressed, various lanthanide ions can added thereby generating a built-in site-specific fluorophore that can be used to monitor protein/protein and protein/ligand interactions. The LBTs also can be used to facilitate structure determination by NMR and X-ray methods.

Selected Publications

  • "Recognition-Domain Focused (RDF) Chemosensors: Versatile and Efficient Reporters of Protein Kinase Activity" Luković, E.; González-Vera, J. A.; Imperiali, B. J. Am. Chem. Soc. 2008, 130, 12821-12827.
  • "A Versatile Amino Acid Analogue of the Solvatochromic Fluorophore 4-N,N-Dimethylamino-1,8-naphthalimide: A Powerful Tool for the Study of Dynamic Protein Interactions" Loving, G. S.; Imperiali, B. J. Am. Chem. Soc. 2008, 130, 13630-13638. 
  • "A General Screening Strategy for Peptide-Based Fluorogenic Ligands: Probes for Dynamic Studies of PDZ Domain-Mediated Interactions”, Sainlos, M.; Iskenderian, W. S.; Imperiali, B. J. Am. Chem. Soc. 2009, 131, 6680-6682.
  • "Monitoring Protein Kinases in Cellular Media with Highly Selective Chimeric Reporters", Lukovic, E.; Vogel Taylor, E.; Imperiali, B. Angew. Chem. Int. Ed. 2009, 48, 6828-6831.
  • "Monitoring Protein Interactions and Dynamics with Solvatochromic Fluorophores" Loving, G. S.; Sainlos, M.; Imperiali, B. Trends in Biotechnol. 2009, 28, 73-83. 
  • "Lanthanide-Tagged Proteins – An Illuminating Partnership" Allen, K. N. Imperiali, B. Current Opin. Chem. Biol. 2010, 14, 247-254
  • "Perturbing the Folding Energy Landscape of the Bacterial Immunity Protein Im7 by Site-Specific N-Linked Glycosylation" Chen, M. M.; Bartlett, A. I.; Nerenberg, P. S.; Friel, C. T.; Hackenberger, C. P. R.; Stultz, C. M.; Radford, S. E.; Imperiali, B. Proc. Natl. Acad. Sci. USA, 2010, 107, 22528-22533.
  • "Biomimetic Divalent Ligands for the Acute Disruption of Synaptic AMPAR Stabilization" Sainlos, M.; Tigaret, C.; Poujol, C.; Olivier, N. B.; Bard, L.; Breillat, C.; Thiolon, K.; Choquet, D.; Imperiali, B. Nature Chemical Biology, 2011, 7, 81-91.

Last Updated: January 31, 2011