Picture of Jon Clardy
Jon Clardy, Ph.D.
Hsien Wu and Daisy Yen Wu 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
Total synthesis reveals atypical atropisomerism in a small-molecule natural product, tryptorubin A.
Authors: Authors: Reisberg SH, Gao Y, Walker AS, Helfrich EJN, Clardy J, Baran PS.
Science
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Molecular messages in human microbiota.
Authors: Authors: Henke MT, Clardy J.
Science
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Pyonitrins A-D: Chimeric Natural Products Produced by Pseudomonas protegens.
Authors: Authors: Mevers E, Saurí J, Helfrich EJN, Henke M, Barns KJ, Bugni TS, Andes D, Currie CR, Clardy J.
J Am Chem Soc
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Ruminococcus gnavus, a member of the human gut microbiome associated with Crohn's disease, produces an inflammatory polysaccharide.
Authors: Authors: Henke MT, Kenny DJ, Cassilly CD, Vlamakis H, Xavier RJ, Clardy J.
Proc Natl Acad Sci U S A
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An elusive electron shuttle from a facultative anaerobe.
Authors: Authors: Mevers E, Su L, Pishchany G, Baruch M, Cornejo J, Hobert E, Dimise E, Ajo-Franklin CM, Clardy J.
Elife
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Metabolites Involved in Immune Evasion by Batrachochytrium dendrobatidis Include the Polyamine Spermidine.
Authors: Authors: Rollins-Smith LA, Ruzzini AC, Fites JS, Reinert LK, Hall EM, Joosse BA, Ravikumar VI, Huebner MI, Aka A, Kehs MH, Gillard BM, Doe E, Tasca JA, Umile TP, Clardy J, Minbiole KPC.
Infect Immun
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GABA-modulating bacteria of the human gut microbiota.
Authors: Authors: Strandwitz P, Kim KH, Terekhova D, Liu JK, Sharma A, Levering J, McDonald D, Dietrich D, Ramadhar TR, Lekbua A, Mroue N, Liston C, Stewart EJ, Dubin MJ, Zengler K, Knight R, Gilbert JA, Clardy J, Lewis K.
Nat Microbiol
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Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering.
Authors: Authors: Helfrich EJN, Lin GM, Voigt CA, Clardy J.
Beilstein J Org Chem
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Microbial community modulates growth of symbiotic fungus required for stingless bee metamorphosis.
Authors: Authors: Paludo CR, Pishchany G, Andrade-Dominguez A, Silva-Junior EA, Menezes C, Nascimento FS, Currie CR, Kolter R, Clardy J, Pupo MT.
PLoS One
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Canvass: A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space.
Authors: Authors: Kearney SE, Zahoránszky-Kohalmi G, Brimacombe KR, Henderson MJ, Lynch C, Zhao T, Wan KK, Itkin Z, Dillon C, Shen M, Cheff DM, Lee TD, Bougie D, Cheng K, Coussens NP, Dorjsuren D, Eastman RT, Huang R, Iannotti MJ, Karavadhi S, Klumpp-Thomas C, Roth JS, Sakamuru S, Sun W, Titus SA, Yasgar A, Zhang YQ, Zhao J, Andrade RB, Brown MK, Burns NZ, Cha JK, Mevers EE, Clardy J, Clement JA, Crooks PA, Cuny GD, Ganor J, Moreno J, Morrill LA, Picazo E, Susick RB, Garg NK, Goess BC, Grossman RB, Hughes CC, Johnston JN, Joullie MM, Kinghorn AD, Kingston DGI, Krische MJ, Kwon O, Maimone TJ, Majumdar S, Maloney KN, Mohamed E, Murphy BT, Nagorny P, Olson DE, Overman LE, Brown LE, Snyder JK, Porco JA, Rivas F, Ross SA, Sarpong R, Sharma I, Shaw JT, Xu Z, Shen B, Shi W, Stephenson CRJ, Verano AL, Tan DS, Tang Y, Taylor RE, Thomson RJ, Vosburg DA, Wu J, Wuest WM, Zakarian A, Zhang Y, Ren T, Zuo Z, Inglese J, Michael S, Simeonov A, Zheng W, Shinn P, Jadhav A, Boxer MB, Hall MD, Xia M, Guha R, Rohde JM.
ACS Cent Sci
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