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
Antiplasmodial activity of piperazine sulfonamides.
Authors: Authors: Martyn DC, Cortese JF, Tyndall E, Dick J, Mazitschek R, Munoz B, Clardy J.
Bioorg Med Chem Lett
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Target identification using drug affinity responsive target stability (DARTS).
Authors: Authors: Lomenick B, Hao R, Jonai N, Chin RM, Aghajan M, Warburton S, Wang J, Wu RP, Gomez F, Loo JA, Wohlschlegel JA, Vondriska TM, Pelletier J, Herschman HR, Clardy J, Clarke CF, Huang J.
Proc Natl Acad Sci U S A
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Bionectriol A, a polyketide glycoside from the fungus Bionectria sp. associated with the fungus-growing ant, Apterostigma dentigerum.
Authors: Authors: Freinkman E, Oh DC, Scott JJ, Currie CR, Clardy J.
Tetrahedron Lett
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Two chemoreceptors mediate developmental effects of dauer pheromone in C. elegans.
Authors: Authors: Kim K, Sato K, Shibuya M, Zeiger DM, Butcher RA, Ragains JR, Clardy J, Touhara K, Sengupta P.
Science
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The ATP-dependent amide ligases DdaG and DdaF assemble the fumaramoyl-dipeptide scaffold of the dapdiamide antibiotics.
Authors: Authors: Hollenhorst MA, Clardy J, Walsh CT.
Biochemistry
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Synthesis and in vitro DMPK profiling of a 1,2-dioxolane-based library with activity against Plasmodium falciparum.
Authors: Authors: Martyn DC, Beletsky G, Cortese JF, Tyndall E, Liu H, Fitzgerald MM, O'Shea TJ, Liang B, Clardy J.
Bioorg Med Chem Lett
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D-amino acids govern stationary phase cell wall remodeling in bacteria.
Authors: Authors: Lam H, Oh DC, Cava F, Takacs CN, Clardy J, de Pedro MA, Waldor MK.
Science
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A stabilized demethoxyviridin derivative inhibits PI3 kinase.
Authors: Authors: Yuan H, Pupo MT, Blois J, Smith A, Weissleder R, Clardy J, Josephson L.
Bioorg Med Chem Lett
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An indole-containing dauer pheromone component with unusual dauer inhibitory activity at higher concentrations.
Authors: Authors: Butcher RA, Ragains JR, Clardy J.
Org Lett
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Natural products: Beyond grind and find.
Authors: Authors: Miller SJ, Clardy J.
Nat Chem
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