个人简介

Education: B.S., 1982, Miami University (Ohio), Ph.D., 1988, Columbia University Awards: 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

研究领域

Bioorganic/Biophysical/Chemical Biology/Organic

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.

近期论文

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Caroline Roost , Stephen R Lynch , Pedro J. Batista , Kun Qu , Howard Y. Chang , and Eric T. Kool,* Structure and Thermodynamics of N6-methyladenosine in RNA: a Spring-Loaded Base Modification, J Am Chem Soc, 2015, epub ahead of print. Dennis Larsen, Michael Pittelkow, Saswata Karmakar, and Eric T. Kool,* New Organocatalyst Scaffolds with High Activity in Promoting Hydrazone and Oxime Formation at Neutral pH, Org Lett, 2015, 17, 274-277. Lik Hang Yuen, Raphael M. Franzini, Samuel S. Tan, and Eric T. Kool,* Large-scale Detection of Metals with a Small Set of Fluorescent DNA-like Chemosensors, J Am Chem Soc, 2014, 136, 14576-14582. Robert C. Spitale, Ryan A. Flynn, Eduardo A. Torre, Eric T. Kool* and Howard Y. Chang, RNA structural analysis by evolving SHAPE chemistry, Wiley Interdiscip Rev RNA, 2014, 5, 867-881. Lik Hang Yuen, Raphael M. Franzini, Shenliang Wang, Pete Crisalli, Vijay Singh, Wei Jiang, and Eric T. Kool,* Pattern-based Detection of Toxic Metals in Surface Water with DNA Polyfluorophores, Angew Chem Int Ed Engl, 2014, 53, 5361-5365. Liang Xu, Linati Da, Steven W. Plouffe, Jenny Chong, Eric Kool,* and Dong Wang, Molecular basis of transcriptional fidelity and DNA lesion-induced transcriptional mutagenesis, DNA Repair (Amst), 2014, 19, 71-83. Liang Xu, Kyle V. Butler, Jenny Chong, Jesper Wengel, Eric T. Kool,* and Dong Wang, Dissecting the chemical interactions and substrate structural signatures governing RNA polymerase II trigger loop closure by synthetic nucleic acid analogues, Nucleic Acids Res, 2014, 42, 5863-5870. Eric T. Kool,* Pete Crisalli, and Ke Min Chan, Fast Alpha Nucleophiles: Structures that Undergo Rapid Hydrazone/Oxime Formation at Neutral pH, Org Lett, 2014, 16, 1454-1457. Emily M. Harcourt, Thomas Ehrenschwender, Pedro J. Batista, Howard Y. Chang, and Eric T. Kool,* Identification of a Selective Polymerase Enables Detection of N6-Methyladenosine in RNA, J Am Chem Soc, 2013, 135, 19079-19082. Malte Winnacker and Eric T. Kool,* Artificial genetic sets composed of size-expanded base pairs, Angew Chem Int Ed Engl, 2013, 52, 12498-12508. Eric T. Kool,* Do-Hyoung Park, and Pete Crisalli, Fast Hydrazone Reactants: Electronic and Acid/Base Effects Strongly Influence Rate at Biological pH, J. Am. Chem. Soc., 2013, 135, 17663-17666. Wei Jiang, Shenliang Wang, Likhang H. Yuen, Hyukin Kwon, Toshikazu Ono, Eric T. Kool,* DNA-polyfluorophore Chemosensors for Environmental Remediation: Vapor-phase Identification of Petroleum Products in Contaminated Soil, Chem. Sci., 2013, 4, 3184-3190. James Attwater, Shunsuke Tagami, Michiko Kimoto, Kyle Butler, Eric T Kool,* Jesper Wengel, Piet Herdewijn, Ichiro Hirao, and Philipp Holliger, Chemical fidelity of an RNA polymerase ribozyme, Chem. Sci., 2013, 4, 2804-2814. Toshikazu Ono, Sarah K. Edwards, Shenliang Wang, Wei Jiang, and Eric T. Kool,* Monitoring eukaryotic and bacterial UDG repair activity with DNA-multifluorophore sensors, Nucleic Acids Res., 2013, 41, e127. Vijay Singh, Shenliang Wang, and Eric T. Kool,* Genetically Encoded Multispectral Labeling of Proteins with Polyfluorophores on a DNA Backbone, J. Am. Chem. Soc., 2013, 16, 6184-6191. Pete Crisalli and Eric T. Kool,* The Importance of ortho Proton Donors in Catalysis of Hydrazone Formation, Org. Lett., 2013, 15, 1646-1649. Jong-Hwa Jung, Sarah K. Edwards and Eric T. Kool,* Selective Fluorogenic Chemosensors for Distinct Classes of Nucleases, ChemBioChem, 2013, 14, 440-444. Pete Crisalli and Eric T. Kool,* Water-soluble Organocatalysts for Hydrazone and Oxime Formation, J. Org. Chem., 2013, 78, 1184-1189. Robert C. Spitale, Pete Crisalli, Ryan A. Flynn, Eduardo A. Torre, Eric T. Kool,* and Howard Y. Chang*, RNA SHAPE Analysis in Living Cells, Nat. Chem. Biol., 2013, 9, 18-20. Pete Crisalli, Armando R. Hernandez, and Eric T. Kool,* Fluorescence Quenchers for Hydrazone and Oxime Orthogonal Bioconjugation, Bioconj. Chem., 2012, 23, 1969-1980.