Picture of Jon Clardy

Jon Clardy, Ph.D.

Christopher T. Walsh Professor of Biological Chemistry and Molecular Pharmacology

The laboratory focuses on biologically active small molecules, especially those from bacteria and fungi with an overall goal of understanding how small molecules control biological processes. 

Research:

The laboratory focuses on biologically active small molecules, especially those from bacteria and fungi with an overall goal of understanding how small molecules control biological processes.  Organizing themes include: 1) function-based discovery of microbially-produced small molecules and their roles in microbial symbioses , 2) function-based discovery of biologically active small molecules using high-throughput screening,  3) genome-based discovery of bacterially-produced small molecules. 

1.  We have focused on the small molecule exchanges that underlie multilateral symbioses involving bacteria, partly because they are widespread and poorly understood and partly because they lead to the discovery of new useful molecules in the biological context in which they evolved.  Current projects involve the bacterial symbionts of fungus-growing ants, members of the human gut microbiome linked to disease, and interactions between micro-algae and bacteria.

2.  We also continue to discover small molecules in a more medically relevant context: high-throughput screening for a variety of diseases.  In these projects we have focused on antibacterial, antifungal, and antiparasitic agents along with immunomodulators and anticancer agents. 

3.  It is now quite clear that well studied bacteria – the producers of drugs that are used on the ton scale, for example – are genetically capable of producing many more potentially useful small molecules.  The biosynthetic gene can be seen but the associated molecules have never been characterized.  Ways to access these cryptic metabolites is a current focus of the laboratory.

Address: 

Room C-643

240 Longwood Avenue

Boston, MA 02115

Publications View
Chemical Exchanges between Multilateral Symbionts.
Authors: Authors: Bae M, Mevers E, Pishchany G, Whaley SG, Rock CO, Andes DR, Currie CR, Pupo MT, Clardy J.
Org Lett
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Pollen Streptomyces Produce Antibiotic That Inhibits the Honey Bee Pathogen Paenibacillus larvae.
Authors: Authors: Grubbs KJ, May DS, Sardina JA, Dermenjian RK, Wyche TP, Pinto-Tomás AA, Clardy J, Currie CR.
Front Microbiol
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Plasmalogen Biosynthesis by Anaerobic Bacteria: Identification of a Two-Gene Operon Responsible for Plasmalogen Production in Clostridium perfringens.
Authors: Authors: Jackson DR, Cassilly CD, Plichta DR, Vlamakis H, Liu H, Melville SB, Xavier RJ, Clardy J.
ACS Chem Biol
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Enteroendocrine cells sense bacterial tryptophan catabolites to activate enteric and vagal neuronal pathways.
Authors: Authors: Ye L, Bae M, Cassilly CD, Jabba SV, Thorpe DW, Martin AM, Lu HY, Wang J, Thompson JD, Lickwar CR, Poss KD, Keating DJ, Jordt SE, Clardy J, Liddle RA, Rawls JF.
Cell Host Microbe
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A conserved coccidian gene is involved in Toxoplasma sensitivity to the anti-apicomplexan compound, tartrolon E.
Authors: Authors: Bowden GD, Reis PM, Rogers MB, Bone Relat RM, Brayton KA, Wilson SK, Di Genova BM, Knoll LJ, Nepveux V FJ, Tai AK, Ramadhar TR, Clardy J, O'Connor RM.
Int J Parasitol Drugs Drug Resist
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A symbiotic bacterium of shipworms produces a compound with broad spectrum anti-apicomplexan activity.
Authors: Authors: O'Connor RM, Nepveux V FJ, Abenoja J, Bowden G, Reis P, Beaushaw J, Bone Relat RM, Driskell I, Gimenez F, Riggs MW, Schaefer DA, Schmidt EW, Lin Z, Distel DL, Clardy J, Ramadhar TR, Allred DR, Fritz HM, Rathod P, Chery L, White J.
PLoS Pathog
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Parsing Molecules for Drug Discovery.
Authors: Authors: Walker AS, Pishchany G, Clardy J.
Biochemistry
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Total synthesis reveals atypical atropisomerism in a small-molecule natural product, tryptorubin A.
Authors: Authors: Reisberg SH, Gao Y, Walker AS, Helfrich EJN, Clardy J, Baran PS.
Science
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Cycloheximide-Producing Streptomyces Associated With Xyleborinus saxesenii and Xyleborus affinis Fungus-Farming Ambrosia Beetles.
Authors: Authors: Grubbs KJ, Surup F, Biedermann PHW, McDonald BR, Klassen JL, Carlson CM, Clardy J, Currie CR.
Front Microbiol
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Molecular messages in human microbiota.
Authors: Authors: Henke MT, Clardy J.
Science
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