George A. and Hilda M. Daubert Professor (b. 1960)
B.S., 1982, Miami University (Ohio), Ph.D., 1988, Columbia University
Office of Naval Research Young Investigator, 1992; Beckman Foundation Young Investigator, 1992; Army Research Office Young Investigator, 1993; Dreyfus Foundation Teacher - Scholar, 1993; American Cyanamid Faculty Award, 1994; Alfred P. Sloan Foundation Fellow, 1994; American Chemical Society Arthur C. Cope Scholar, 2000; American Chemical Society Pfizer Award, 2000; Dean's Award for Distinguished Teaching, 2001; AAAS Fellow, 2002; Dean's Award for Distinguished Teaching, 2014; Ronald Breslow Award for Achievement in Biomimetic Chemistry, 2015

Chemistry Research Area: 
Chemistry Research Area: 
Chemistry Research Area: 
Chemical Biology
Chemistry Research Area: 

Principal Research Interests

A chief focus of research in our laboratory is on design, synthesis, and study of molecules that function in biological systems. The research can lead to basic understanding of biological mechanisms such as DNA repair and RNA modification, and to the development of molecules for detecting and treating disease.
One long-term goal of the group is the design and discovery of new chemistries and molecules that can react within cells to probe or report on DNA and RNA sequence or structure. For example, we have developed novel small-molecule reagents that have enabled the in vivo mapping of RNA structure genome-wide, and reactive molecules that identify specific modified bases in cellular RNA. We are developing new covalent modification chemistries for attaching reporters to RNAs and proteins, and templated chemistries that report on specific RNA sequences with a fluorescent signal.
A second project involves the development of fluorescent molecular assemblies built on a DNA scaffold. We synthesize new fluorescent nucleosides that can be strung together with a DNA synthesizer. These oligomers are assembled into DNA-like libraries and are being evaluated for unusual fluorescence and sensing properties. Using this design, we have successfully developed intracellular sensors of several classes of enzymes, including esterases, proteases, and DNA repair enzymes. These DNA-like molecules are under development as new tools for biological reporting in cells.
A third research goal involves the design of new bases for DNA and RNA. Our group was the first to show that DNA base pairs could be replicated very efficiently by polymerase enzymes even when they lack Watson-Crick hydrogen bonds. As a result, we are now developing new DNA and RNA bases with varied structures, sizes, and shapes. New bases and base pairs can be used as mechanistic tools for the study of basic biology and medicine, to expand nature's genetic system, or to develop entirely new genetic systems.

Representative Publications

 1)  “Structure and Thermodynamics of N6-methyladenosine in RNA: a Spring-Loaded Base Modification,” C. Roost, S.M. Lynch, P.J. Batista, K. Qu, H.Y. Chang, E.T. Kool, J. Am. Chem. Soc., 2015, in press
2) “Large-scale Detection of Metals with a Small Number of DNA-like Fluorescent Chemosensors,” L.-H. Yuen, R.M. Franzini, S.S. Tan, E.T. Kool, J. Am. Chem. Soc., 136, 14576-14582 (2014).

3)  “Artificial Genetic Sets Composed of Size-Expanded Base Pairs,” M. Winnacker, E.T. Kool, Angew. Chem. Int. Ed., 52, 12498-12508 (2013).

4)  “Genetically Encoded Multispectral Labeling of Proteins with Polyfluorophores on a DNA Backbone,” V. Singh, S. Wang, E.T. Kool, J. Am. Chem. Soc., 135, 6184-6191 (2013).

5)  “Selective Fluorogenic Chemosensors for Distinct Classes of Nucleases,” J.-W. Jung, Sarah K. Edwards, Eric T. Kool, ChemBioChem, 14, 440-444 (2013).

6)  “Efficient Water-soluble Organocatalysts for Hydrazone and Oxime Formation,” P. Crisalli, E.T. Kool, J. Org. Chem., 78, 1184-1189 (2013).

7)  “RNA SHAPE Analysis in Living Cells,” R.C. Spitale, P. Crisalli, R.A. Flynn, E.A. Torre, E.T. Kool, H.Y. Chang, Nature Chem. Biol., 9, 18-20 (2012).

8)  “Templated Chemistry for Monitoring Damage and Repair Directly in Duplex DNA,” S.H. Lee, S. Wang, E.T. Kool, Chem. Commun., 48, 8069-8071 (2012).

9)  “Surprising Repair Activities of Nonpolar Analogs of 8-oxoG Expose Features of Recognition and Catalysis by Base Excision Repair Glycosylases,” P.L. McKibbin, A. Kobori, Y. Taniguchi, E.T. Kool, S.S. David, J. Am. Chem. Soc., 134, 1653-1661 (2012).
10)  “Direct Fluorescence Monitoring of DNA Base Excision Repair,” T. Ono, S. Wang, C-K. Koo, L. Engstrom, S.S. David, E.T. Kool, Angew. Chem. Int. Ed., 51, 1689-1693 (2012).