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
FOXO3a is broadly neuroprotective in vitro and in vivo against insults implicated in motor neuron diseases.
Authors: Authors: Mojsilovic-Petrovic J, Nedelsky N, Boccitto M, Mano I, Georgiades SN, Zhou W, Liu Y, Neve RL, Taylor JP, Driscoll M, Clardy J, Merry D, Kalb RG.
J Neurosci
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The natural history of antibiotics.
Authors: Authors: Clardy J, Fischbach MA, Currie CR.
Curr Biol
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Dentigerumycin: a bacterial mediator of an ant-fungus symbiosis.
Authors: Authors: Oh DC, Poulsen M, Currie CR, Clardy J.
Nat Chem Biol
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Colorimetric high-throughput screen for detection of heme crystallization inhibitors.
Authors: Authors: Rush MA, Baniecki ML, Mazitschek R, Cortese JF, Wiegand R, Clardy J, Wirth DF.
Antimicrob Agents Chemother
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Progestins activate the AKT pathway in leiomyoma cells and promote survival.
Authors: Authors: Hoekstra AV, Sefton EC, Berry E, Lu Z, Hardt J, Marsh E, Yin P, Clardy J, Chakravarti D, Bulun S, Kim JJ.
J Clin Endocrinol Metab
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A hub-and-spoke circuit drives pheromone attraction and social behaviour in C. elegans.
Authors: Authors: Macosko EZ, Pokala N, Feinberg EH, Chalasani SH, Butcher RA, Clardy J, Bargmann CI.
Nature
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Identification and characterization of small molecule inhibitors of a class I histone deacetylase from Plasmodium falciparum.
Authors: Authors: Patel V, Mazitschek R, Coleman B, Nguyen C, Urgaonkar S, Cortese J, Barker RH, Greenberg E, Tang W, Bradner JE, Schreiber SL, Duraisingh MT, Wirth DF, Clardy J.
J Med Chem
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Thirteen posttranslational modifications convert a 14-residue peptide into the antibiotic thiocillin.
Authors: Authors: Wieland Brown LC, Acker MG, Clardy J, Walsh CT, Fischbach MA.
Proc Natl Acad Sci U S A
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Biosynthesis of the Caenorhabditis elegans dauer pheromone.
Authors: Authors: Butcher RA, Ragains JR, Li W, Ruvkun G, Clardy J, Mak HY.
Proc Natl Acad Sci U S A
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Mycangimycin, a polyene peroxide from a mutualist Streptomyces sp.
Authors: Authors: Oh DC, Scott JJ, Currie CR, Clardy J.
Org Lett
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