Jason M. Crawford

Research

The Crawford laboratory is developing and systematically applying genome sequence-guided methods for the discovery of genetically encoded small molecules from mutualistic and pathogenic microorganisms. High-throughput genome sequencing of bacteria and fungi has revealed many highly unusual “orphan” biosynthetic gene clusters suspected of synthesizing novel, structurally diverse, and biologically active small molecules. These types of naturally produced molecules often regulate complex interactions with their animal hosts, hold a rich history of being utilized as human drugs, and serve as excellent molecular probes for identifying new drug targets for a wide variety of diseases. Using a blend of small molecule chemistry, protein biochemistry, cell biology, and microbiology, the lab exploits the natural interactions between bacteria and animals to discover new molecules with signaling, antimicrobial, immunosuppressant, and anticancer activities, connects them to their underlying biosynthetic gene clusters, characterizes and engineers the biosynthetic enzymes involved in their construction, and investigates their roles in biology and medicine.

Education

Ph.D. Johns Hopkins University, 2007
Postdoctoral Fellowship, Harvard Medical School, 2007-2011

Honors

• Sarah and Adolph Roseman Achievement Award, 2007
• Damon Runyon Cancer Research Foundation Postdoctoral Fellowship, 2009-2011
• National Institutes of Health Pathway to Independence Award, Yale University, 2011
• Member, Yale Chemical Biology Institute, 2012-present 
• Damon Runyon Cancer Research Foundation Dale F. Frey Award for Breakthrough Scientists, 2012
• Searle Scholars Award, 2013
• National Institutes of Health New Innovator Award, 2013
• Member, Faculty of 1000, Chemical Biology, Small Molecule Chemistry section, 2013-present
• Yale Cancer Center Pilot Project Award, 2015, 2018
• Damon Runyon-Rachleff Innovation Award, 2016
• Yale Pepper Center Pilot Project Award, 2016
• Camille & Henry Dreyfus Teacher-Scholar Award, 2017
• Burroughs Wellcome Investigators in the Pathogenesis of Infectious Disease (PATH) Award, 2017
• Maxine F. Singer ‘57 PhD endowed Chair, 2018
• American Society of Pharmacognosy Matt Suffness Award, 2021

Recent Publications

Patel, J.R.*, Oh, J.*, Wang, S., Crawford, J.M.†, Isaacs, F.J.† 2022. Cross-kingdom expression of synthetic genetic elements promotes discovery of metabolites in the human microbiome. Cell. 185(9): 1487-1505.  

Shine, E.E., Crawford, J.M.†  2021. Molecules from the Microbiome.  Annual Rev Biochem. 90: 789-815.

Li, J.-H.*, Oh, J.*, Kienesberger, S., Kim, N.Y., Clarke, D.J., Zechner, E.L., Crawford, J.M.† 2020. Making and breaking leupeptin protease inhibitors in pathogenic gammaproteobacteria. Angew. Chem. Int. Ed. 59(41): 17872-17880.

Park, H.B.*, Wei, Z.*, Oh, J., Xu, H., Kim, C.S., Wang, R., Wyche, T.P., Piizzi, G., Flavell, R.A.†, Crawford, J.M.†  2020. Sulfamethoxazole drug stress upregulates antioxidant immunomodulatory metabolites in Escherichia coli. Nature Micro.  5: 1319-1329.

Park, H.B.*, Goddard, T.N.*, Oh, J., Patel, J., Wei, Z., Perez, C.E., Mercado, B.Q., Wang, R., Wyche, T.P., Piizzi, G., Flavell, R.A., Crawford, J.M.†  2020. Bacterial autoimmune drug metabolism transforms an immunomodulator into structurally and functionally divergent antibiotics. Angew. Chem. Int. Ed.  59(20): 7871-7880.

Kim, C.S., Gatsios, A., Cuesta, S., Lam, Y.C., Wei, Z., Chen, H., Russell, R.M., Shine, E.E., Wang, R., Wyche, T.P., Piizzi, G., Flavell, R.A., Palm, N.W., Sperandio, V., Crawford, J.M.† 2020. Characterization of autoinducer-3 structure and biosynthesis in E. coli. ACS Central Science.  6(2): 197-206.  

Xue, M.*, Kim, C.S.*, Healy, A.R., Wernke, K.M., Wang, Z., Frischling, M.C., Shine, E.E., Wang, W., Herzon, S.B.†, Crawford, J.M.† 2019. Structure elucidation of colibactin and its DNA crosslinks. Science. 365(6457): eaax2685.  

† = corresponding author
* = co-first author