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
Using the heat-shock response to discover anticancer compounds that target protein homeostasis.
Authors: Authors: Santagata S, Xu YM, Wijeratne EM, Kontnik R, Rooney C, Perley CC, Kwon H, Clardy J, Kesari S, Whitesell L, Lindquist S, Gunatilaka AA.
ACS Chem Biol
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A high-throughput screen identifies a new natural product with broad-spectrum antibacterial activity.
Authors: Authors: Ymele-Leki P, Cao S, Sharp J, Lambert KG, McAdam AJ, Husson RN, Tamayo G, Clardy J, Watnick PI.
PLoS One
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Old meets new: using interspecies interactions to detect secondary metabolite production in actinomycetes.
Authors: Authors: Seyedsayamdost MR, Traxler MF, Clardy J, Kolter R.
Methods Enzymol
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Selection for high oridonin yield in the Chinese medicinal plant Isodon (Lamiaceae) using a combined phylogenetics and population genetics approach.
Authors: Authors: Harris ES, Cao S, Schoville SD, Dong C, Wang W, Jian Z, Zhao Z, Eisenberg DM, Clardy J.
PLoS One
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Catecholate siderophores protect bacteria from pyochelin toxicity.
Authors: Authors: Adler C, Corbalán NS, Seyedsayamdost MR, Pomares MF, de Cristóbal RE, Clardy J, Kolter R, Vincent PA.
PLoS One
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Identification and validation of tetracyclic benzothiazepines as Plasmodium falciparum cytochrome bc1 inhibitors.
Authors: Authors: Dong CK, Urgaonkar S, Cortese JF, Gamo FJ, Garcia-Bustos JF, Lafuente MJ, Patel V, Ross L, Coleman BI, Derbyshire ER, Clish CB, Serrano AE, Cromwell M, Barker RH, Dvorin JD, Duraisingh MT, Wirth DF, Clardy J, Mazitschek R.
Chem Biol
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Roseobacticides: small molecule modulators of an algal-bacterial symbiosis.
Authors: Authors: Seyedsayamdost MR, Carr G, Kolter R, Clardy J.
J Am Chem Soc
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NRPS substrate promiscuity diversifies the xenematides.
Authors: Authors: Crawford JM, Portmann C, Kontnik R, Walsh CT, Clardy J.
Org Lett
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Dihydrophenylalanine: a prephenate-derived Photorhabdus luminescens antibiotic and intermediate in dihydrostilbene biosynthesis.
Authors: Authors: Crawford JM, Mahlstedt SA, Malcolmson SJ, Clardy J, Walsh CT.
Chem Biol
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Heavy metal and pesticide content in commonly prescribed individual raw Chinese Herbal Medicines.
Authors: Authors: Harris ES, Cao S, Littlefield BA, Craycroft JA, Scholten R, Kaptchuk T, Fu Y, Wang W, Liu Y, Chen H, Zhao Z, Clardy J, Woolf AD, Eisenberg DM.
Sci Total Environ
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