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
Berkeleydione and berkeleytrione, new bioactive metabolites from an acid mine organism.
Authors: Authors: Stierle DB, Stierle AA, Hobbs JD, Stokken J, Clardy J.
Org Lett
View full abstract on Pubmed
A further study of the cytotoxic constituents of a milnamide-producing sponge.
Authors: Authors: Sonnenschein RN, Farias JJ, Tenney K, Mooberry SL, Lobkovsky E, Clardy J, Crews P.
Org Lett
View full abstract on Pubmed
A chemical genetic screen identifies inhibitors of regulated nuclear export of a Forkhead transcription factor in PTEN-deficient tumor cells.
Authors: Authors: Kau TR, Schroeder F, Ramaswamy S, Wojciechowski CL, Zhao JJ, Roberts TM, Clardy J, Sellers WR, Silver PA.
Cancer Cell
View full abstract on Pubmed
Unusual C25 steroids produced by a sponge-derived Penicillium citrinum.
Authors: Authors: Amagata T, Amagata A, Tenney K, Valeriote FA, Lobkovsky E, Clardy J, Crews P.
Org Lett
View full abstract on Pubmed
The crystal structure of palmitoyl protein thioesterase-2 (PPT2) reveals the basis for divergent substrate specificities of the two lysosomal thioesterases, PPT1 and PPT2.
Authors: Authors: Calero G, Gupta P, Nonato MC, Tandel S, Biehl ER, Hofmann SL, Clardy J.
J Biol Chem
View full abstract on Pubmed
Structural and functional analysis of pantocin A: an antibiotic from Pantoea agglomerans discovered by heterologous expression of cloned genes.
Authors: Authors: Jin M, Liu L, Wright SA, Beer SV, Clardy J.
Angew Chem Int Ed Engl
View full abstract on Pubmed
The biosynthetic gene cluster of Pantocin a provides insights into biosynthesis and a tool for screening.
Authors: Authors: Jin M, Wright SA, Beer SV, Clardy J.
Angew Chem Int Ed Engl
View full abstract on Pubmed
Isolation and structural proof of the large diamond molecule, cyclohexamantane (C26H30).
Authors: Authors: Dahl JE, Moldowan JM, Peakman TM, Clardy JC, Lobkovsky E, Olmstead MM, May PW, Davis TJ, Steeds JW, Peters KE, Pepper A, Ekuan A, Carlson RM.
Angew Chem Int Ed Engl
View full abstract on Pubmed
Trichodermamides A and B, cytotoxic modified dipeptides from the marine-derived fungus Trichoderma virens.
Authors: Authors: Garo E, Starks CM, Jensen PR, Fenical W, Lobkovsky E, Clardy J.
J Nat Prod
View full abstract on Pubmed
Structure of the large FK506-binding protein FKBP51, an Hsp90-binding protein and a component of steroid receptor complexes.
Authors: Authors: Sinars CR, Cheung-Flynn J, Rimerman RA, Scammell JG, Smith DF, Clardy J.
Proc Natl Acad Sci U S A
View full abstract on Pubmed