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
Crystal structure of P13K SH3 domain at 20 angstroms resolution.
Authors: Authors: Liang J, Chen JK, Schreiber ST, Clardy J.
J Mol Biol
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Structure of the spiroketal-macrolide ossamycin.
Authors: Authors: Kirst HA, Mynderse JS, Martin JW, Baker PJ, Paschal JW, Rios Steiner JL, Lobkovsky E, Clardy J.
J Antibiot (Tokyo)
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Crystallization and preliminary X-ray analysis of twinned crystals of a chimeric FK506 binding protein 12 and 13 complexed with FK506.
Authors: Authors: Liang J, Ealick S, Nielsen C, Schreiber SL, Clardy J.
Acta Crystallogr D Biol Crystallogr
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The relationship between an endangered North American tree and an endophytic fungus.
Authors: Authors: Lee JC, Yang X, Schwartz M, Strobel G, Clardy J.
Chem Biol
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Topoisomerase II-mediated DNA cleavage by adocia- and xestoquinones from the Philippine sponge Xestospongia sp.
Authors: Authors: Concepción GP, Foderaro TA, Eldredge GS, Lobkovsky E, Clardy J, Barrows LR, Ireland CM.
J Med Chem
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Structure of the new spiroketal-macrolide A82548A.
Authors: Authors: Kirst HA, Larsen SH, Paschal JW, Occolowitz JL, Creemer LC, Steiner JL, Lobkovsky E, Clardy J.
J Antibiot (Tokyo)
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New insight into the catalytic mechanism of chorismate mutases from structural studies.
Authors: Authors: Lee AY, Stewart JD, Clardy J, Ganem B.
Chem Biol
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9,11-Secogorgost-5-en-9-one-3 beta,11-diol, a marine steroid from the sea whip Pseudopterogorgia hummelinkii.
Authors: Authors: Schultz LW, Clardy J, Lessinger L.
Acta Crystallogr C
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The chemistry of signal transduction.
Authors: Authors: Clardy J.
Proc Natl Acad Sci U S A
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Isolation and structure/activity features of halomon-related antitumor monoterpenes from the red alga Portieria hornemannii.
Authors: Authors: Fuller RW, Cardellina JH, Jurek J, Scheuer PJ, Alvarado-Lindner B, McGuire M, Gray GN, Steiner JR, Clardy J, Menez E, et al.
J Med Chem
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