个人简介

B.A. 1994, Oberlin College Ph.D. 1999, California Institute of Technology Postdoctoral Fellow at Harvard University, 1999-2002 .

研究领域

Chemical Biology/Organic

Organic chemistry is in the unique position to provide molecular level insights into biological processes. Renewed appreciation for the power of small molecules as tools to explore living systems has fueled an explosion of interest in chemical biology. Within this broad context, our research program is focused on the development of new synthetic methodology to expedite the discovery of biologically active molecules. We are strategically combining elements of microwave-assisted organic chemistry, solid-phase synthesis, and combinatorial chemistry to provide access to new classes of chemical probes. In turn, we are applying these small molecule tools to bacterial communication and host/microbe interactions, previously unexamined areas of chemical biology. We seek to understand how both plants and animals sense and respond to invasion by pathogenic microbes. The ability of bacteria to communicate with each other and function as a group is a critical step in the development of infectious disease. The reliance of bacteria on a language of small molecules places organic chemists in a unique position to discover the fundamental principles underlying this communication network and design tools to modulate it at the molecular level.

近期论文

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J. P. Gerdt, C. E. McInnis, T. L. Schell, and H. E. Blackwell. "Unraveling the contributions of hydrogen-bonding interactions to the activity of native and non-native ligands in the quorum-sensing receptor LasR." Org. Biomol. Chem. 2015, 13, 1453-1462. (DOI 10.1039/C4OB02252A) M. A. Welsh, N. R. Eibergen, J. D. Moore, and H. E. Blackwell. "Small molecule disruption of quorum sensing cross-regulation in Pseudomonas aeruginosa causes major and unexpected alterations to virulence phenotypes." J. Am. Chem. Soc. 2015, 137, 1510-1519. (DOI 10.1021/ja5110798) A. H. Broderick, D. M. Stacy, Y. Tal-Gan, M. J. Kratochvil, H. E. Blackwell, and D. M. Lynn. "Surface Coatings that Promote Rapid Release of Peptide-Based AgrC Inhibitors for Attenuation of Quorum Sensing in Staphylococcus aureus." Adv. Healthcare Mater. 2014, 3, 97-105. (DOI 10.1002/adhm.201300119) C. E. McInnis and H. E. Blackwell. "Non-Native N-Aroyl L-Homoserine Lactones Are Potent Modulators of the Quorum Sensing Receptor RpaR in Rhodopseudomonas palustris." ChemBioChem. 2014, 15, 87-93. (DOI 10.1002/cbic.201300570) J. D. Moore, J. P. Gerdt, N. R. Eibergen, and H. E. Blackwell. "Active Efflux Influences the Potency of Quorum Sensing Inhibitors in Pseudomonas aeruginosa." ChemBioChem. 2014, 15, 435-442. (DOI 10.1002/cbic.201300701) Y. Tal-Gan, D. M. Stacy, and H. E. Blackwell. "N-Methyl and Peptoid Scans of an Autoinducing Peptide Reveal New Structural Features Required for Inhibition and Activation of AgrC Quorum Sensing Receptors in Staphylococcus aureus." Chem. Commun. 2014, 50, 3000-3003. (DOI 10.1039/C4CC00117F) A. G. Palmer, A. Senechal, A. Mukherjee, J.-M. Ané, and H. E. Blackwell. "Plant Responses to Bacterial N-Acyl L-Homoserine Lactones are Dependent on Enzymatic Degradation to L-Homoserine." ACS Chem. Biol. 2014, 9, 1834-1845. (DOI 10.1021/cb500191a) J. P. Gerdt and H. E. Blackwell. "Competition studies confirm two major barriers that can preclude the spread of resistance to quorum-sensing inhibitors in bacteria." ACS Chem. Biol. 2014, 9, 2291-2299. (DOI 10.1021/cb5004288) J. P. Gerdt, C. E. McInnis, T. L. Schell, F. M. Rossi, and H. E. Blackwell. "Mutational Analysis of the Quorum-Sensing Receptor LasR Reveals Interactions that Govern Activation and Inhibition by Nonlactone Ligands."Chem. Biol. 2014, 21, 1361-1369. (DOI 10.1016/j.chembiol.2014.08.008) A. H. Broderick, A. S. Breitbach, R. Frei, H. E. Blackwell, and D. M. Lynn. “Surface-Mediated Release of a Small-Molecule Modulator of Bacterial Biofilm Formation: A Non-Bactericidal Approach to Inhibiting Biofilm Formation in Pseudomonas aeruginosa.” Adv. Healthcare Mater. 2013, 2, 993-1000. (DOI 10.1002/adhm.201200334) J.A. Crapster and H.E. Blackwell. "A Peptoid Ribbon Secondary Structure." Angew. Chemie. 2013, 52, 5079-5084. (DOI 10.1002/anie.201208630) D. M. Stacy, S. T. Le Quement, C. L. Hansen, J. W. Clausen, T. Tolker-Nielsen, J. W. Brummond, M. Givskov, T. E. Nielsen, and H. E. Blackwell. “Synthesis and Biological Evaluation of Triazole-Containing N-Acyl Homoserine Lactones as Quorum Sensing Modulators.” Org. Biomol. Chem. 2013, 11, 938-954. (DOI 10.1039/C2OB27155A) Y. Tal-Gan, M. Ivancic, G. Cornilescu, C. Cornilescu, and H. E. Blackwell. "Structural Characterization of Native Autoinducing Peptides and Abiotic Analogs Reveals Key Features Essential for Activation and Inhibition of an AgrC Quorum Sensing Receptor in Staphylococcus aureus." J. Am. Chem. Soc. 2013, 135, 18436–18444. (DOI 10.1021/ja407533e) Y. Tal-Gan, D. M. Stacy, M. K. Foegen, D. W. Koenig, and H. E. Blackwell. “Highly Potent Inhibitors of Quorum Sensing in Staphylococcus aureus Revealed Through a Systematic Synthetic Study of the Group-III Autoinducing Peptide.” J. Am. Chem. Soc. 2013, 135, 7869-7882. (DOI 10.1021/ja3112115) D. M. Stacy, M. A. Welsh, P. N. Rather, and H. E. Blackwell. "Attenuation of quorum sensing in the pathogen Acinetobacter baumannii using non-native N-acyl homoserine lactones." ACS Chem. Biol. 2012, 7, 1719-1728. (DOI 10.1021/cb300351x) T. Praneenararat, A. G. Palmer, and H. E. Blackwell. “Chemical Methods to Interrogate Bacterial Quorum Sensing Pathways.” Org. Biomol. Chem. 2012, 10, 8189-8199. (DOI 10.1039/C2OB26353J) A. G. Palmer, E. Streng, and H. E. Blackwell. “Attenuation of virulence in pathogenic bacteria using synthetic quorum-sensing modulators under native conditions on plant hosts.” ACS Chem. Biol. 2012, 6, 1348-1356. (DOI 10.1021/cb200298g) R. Frei, A. S. Breitbach, and H. E. Blackwell. "Expedient Construction of Small-Molecule Macroarrays via Sequential Palladium- and Copper-Mediated Reactions and Their ex situ Biological Testing" Chem. Sci. 2012, 3, 1555-1561. (DOI 10.1039/C2SC01089E) R. Frei, A. S. Breitbach, and H. E. Blackwell. "2-Aminobenzimidazole Derivatives Strongly Inhibit and Disperse Pseudomonas aeruginosa Biofilms" Angew. Chem. Int. Ed. Engl. 2012, 51, 5226-5229. (DOI 10.1002/anie.201109258) A. G. Palmer, E. Streng, K. A. Jewell, and H. E. Blackwell. "Quorum Sensing in Bacterial Species that Use Degenerate Autoinducers Can Be Tuned by Using Structurally Identical Non-native Ligands" ChemBioChem. 2011, 12, 138-147. (DOI 10.1002/cbic.201000551)