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
High-throughput screening affords novel and selective trypanothione reductase inhibitors with anti-trypanosomal activity.
Authors: Authors: Martyn DC, Jones DC, Fairlamb AH, Clardy J.
Bioorg Med Chem Lett
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High-throughput Plasmodium falciparum growth assay for malaria drug discovery.
Authors: Authors: Baniecki ML, Wirth DF, Clardy J.
Antimicrob Agents Chemother
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The identification of bacillaene, the product of the PksX megacomplex in Bacillus subtilis.
Authors: Authors: Butcher RA, Schroeder FC, Fischbach MA, Straight PD, Kolter R, Walsh CT, Clardy J.
Proc Natl Acad Sci U S A
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Differential analysis of 2D NMR spectra: new natural products from a pilot-scale fungal extract library.
Authors: Authors: Schroeder FC, Gibson DM, Churchill AC, Sojikul P, Wursthorn EJ, Krasnoff SB, Clardy J.
Angew Chem Int Ed Engl
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New antibiotics from bacterial natural products.
Authors: Authors: Clardy J, Fischbach MA, Walsh CT.
Nat Biotechnol
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A chemical study of cyclic depsipeptides produced by a sponge-derived fungus.
Authors: Authors: Amagata T, Morinaka BI, Amagata A, Tenney K, Valeriote FA, Lobkovsky E, Clardy J, Crews P.
J Nat Prod
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Bisandrographolide from Andrographis paniculata activates TRPV4 channels.
Authors: Authors: Smith PL, Maloney KN, Pothen RG, Clardy J, Clapham DE.
J Biol Chem
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Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators.
Authors: Authors: Hieronymus H, Lamb J, Ross KN, Peng XP, Clement C, Rodina A, Nieto M, Du J, Stegmaier K, Raj SM, Maloney KN, Clardy J, Hahn WC, Chiosis G, Golub TR.
Cancer Cell
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Preparation of a psammaplysene-based library.
Authors: Authors: Georgiades SN, Clardy J.
Org Lett
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FeeM, an N-acyl amino acid synthase from an uncultured soil microbe: structure, mechanism, and acyl carrier protein binding.
Authors: Authors: Van Wagoner RM, Clardy J.
Structure
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