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
Variable genetic architectures produce virtually identical molecules in bacterial symbionts of fungus-growing ants.
Authors: Authors: Sit CS, Ruzzini AC, Van Arnam EB, Ramadhar TR, Currie CR, Clardy J.
Proc Natl Acad Sci U S A
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Actinoramide A Identified as a Potent Antimalarial from Titration-Based Screening of Marine Natural Product Extracts.
Authors: Authors: Cheng KC, Cao S, Raveh A, MacArthur R, Dranchak P, Chlipala G, Okoneski MT, Guha R, Eastman RT, Yuan J, Schultz PJ, Su XZ, Tamayo-Castillo G, Matainaho T, Clardy J, Sherman DH, Inglese J.
J Nat Prod
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Identification of a Dual Inhibitor of Janus Kinase 2 (JAK2) and p70 Ribosomal S6 Kinase1 (S6K1) Pathways.
Authors: Authors: Byun S, Lim S, Mun JY, Kim KH, Ramadhar TR, Farrand L, Shin SH, Thimmegowda NR, Lee HJ, Frank DA, Clardy J, Lee SW, Lee KW.
J Biol Chem
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Small-Molecule Reactivation of Mutant p53 to Wild-Type-like p53 through the p53-Hsp40 Regulatory Axis.
Authors: Authors: Hiraki M, Hwang SY, Cao S, Ramadhar TR, Byun S, Yoon KW, Lee JH, Chu K, Gurkar AU, Kolev V, Zhang J, Namba T, Murphy ME, Newman DJ, Mandinova A, Clardy J, Lee SW.
Chem Biol
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Minimum Information about a Biosynthetic Gene cluster.
Authors: Authors: Medema MH, Kottmann R, Yilmaz P, Cummings M, Biggins JB, Blin K, de Bruijn I, Chooi YH, Claesen J, Coates RC, Cruz-Morales P, Duddela S, Düsterhus S, Edwards DJ, Fewer DP, Garg N, Geiger C, Gomez-Escribano JP, Greule A, Hadjithomas M, Haines AS, Helfrich EJ, Hillwig ML, Ishida K, Jones AC, Jones CS, Jungmann K, Kegler C, Kim HU, Kötter P, Krug D, Masschelein J, Melnik AV, Mantovani SM, Monroe EA, Moore M, Moss N, Nützmann HW, Pan G, Pati A, Petras D, Reen FJ, Rosconi F, Rui Z, Tian Z, Tobias NJ, Tsunematsu Y, Wiemann P, Wyckoff E, Yan X, Yim G, Yu F, Xie Y, Aigle B, Apel AK, Balibar CJ, Balskus EP, Barona-Gómez F, Bechthold A, Bode HB, Borriss R, Brady SF, Brakhage AA, Caffrey P, Cheng YQ, Clardy J, Cox RJ, De Mot R, Donadio S, Donia MS, van der Donk WA, Dorrestein PC, Doyle S, Driessen AJ, Ehling-Schulz M, Entian KD, Fischbach MA, Gerwick L, Gerwick WH, Gross H, Gust B, Hertweck C, Höfte M, Jensen SE, Ju J, Katz L, Kaysser L, Klassen JL, Keller NP, Kormanec J, Kuipers OP, Kuzuyama T, Kyrpides NC, Kwon HJ, Lautru S, Lavigne R, Lee CY, Linquan B, Liu X, Liu W, Luzhetskyy A, Mahmud T, Mast Y, Méndez C, Metsä-Ketelä M, Micklefield J, Mitchell DA, Moore BS, Moreira LM, Müller R, Neilan BA, Nett M, Nielsen J, O'Gara F, Oikawa H, Osbourn A, Osburne MS, Ostash B, Payne SM, Pernodet JL, Petricek M, Piel J, Ploux O, Raaijmakers JM, Salas JA, Schmitt EK, Scott B, Seipke RF, Shen B, Sherman DH, Sivonen K, Smanski MJ, Sosio M, Stegmann E, Süssmuth RD, Tahlan K, Thomas CM, Tang Y, Truman AW, Viaud M, Walton JD, Walsh CT, Weber T, van Wezel GP, Wilkinson B, Willey JM, Wohlleben W, Wright GD, Ziemert N, Zhang C, Zotchev SB, Breitling R, Takano E, Glöckner FO.
Nat Chem Biol
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A new antibacterial octaketide and cytotoxic phenylethanoid glycosides from Pogostemon cablin (Blanco) Benth.
Authors: Authors: Kim KH, Beemelmanns C, Clardy J, Cao S.
Bioorg Med Chem Lett
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Animals in a bacterial world: opportunities for chemical ecology.
Authors: Authors: Cantley AM, Clardy J.
Nat Prod Rep
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The crystalline sponge method: MOF terminal ligand effects.
Authors: Authors: Ramadhar TR, Zheng SL, Chen YS, Clardy J.
Chem Commun (Camb)
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The cytoplasmic prolyl-tRNA synthetase of the malaria parasite is a dual-stage target of febrifugine and its analogs.
Authors: Authors: Herman JD, Pepper LR, Cortese JF, Estiu G, Galinsky K, Zuzarte-Luis V, Derbyshire ER, Ribacke U, Lukens AK, Santos SA, Patel V, Clish CB, Sullivan WJ, Zhou H, Bopp SE, Schimmel P, Lindquist S, Clardy J, Mota MM, Keller TL, Whitman M, Wiest O, Wirth DF, Mazitschek R.
Sci Transl Med
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Chakyunglupulins A and B, two novel 4,8,8-trimethylcyclooct-2-enone derivatives from Barleria lupulina.
Authors: Authors: Kim KH, Clardy J, Senger D, Cao S.
Tetrahedron Lett
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