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massachusetts institute of technology

Research in the Dedon Lab focuses on the chemical biology of nucleic acids in three broad areas: epigenetics, epitranscriptomics, and genetic toxicology.

Microbial and human epigenetics and epitranscriptomics

tRNA imageThough DNA and RNA modifications have been known for many decades, the emergence of systems-level "'omic" technologies has revealed new functions for post-synthetic nucleic acid modifications that leave the underlying genetic code unchanged. The epigenome of ~20 DNA modifications schedules transcription and mediates in microbial immunity, while the epitranscriptome schedules translation, with >140 chemical modifications of all forms of RNA.

The Dedon Lab and our many collaborators have developed a variety of analytical and informatic platforms for discovery science in epigenetics and epitranscriptomics in infectious disease, antimicrobial resistance, the human microbiome, and cancer and age-related diseases. One platform coordinates comparative genomics, single-molecule real-time sequencing, and mass spectrometry to discover novel DNA modifications, such as phosphorothioate and 7-deazaguanine modifications in bacterial and bacteriophage genomes. Work in bacteriophage points to a tremendous variety of DNA modifications with implications for biotechnology, synthetic biology, and human health and disease. For example, we have found oxidation-sensitive phosphorothioate DNA modifications in 10-20% of the organisms in the human microbiome.

In the realm of the epitranscriptome, we have applied systems-level analytics to discover a mechanism of translational modulation of gene expression common to humans, parasites, yeast, bacteria, and viruses. Here, environmental stressors cause a "reprogramming" of dozens of tRNA modifications to facilitate selective translation of codon-biased mRNAs critical to the cell stress response and survival, with families of stress-response genes defined by unique biases in the use of synonymous codons.

DNAThe Dedon Lab is now leveraging these epigenetic and epitranscriptomic discoveries to develop enzymatic tools for biotechnology, methods for industrial microbiology and protein production, and new antimicrobial agents.

Inflammation and genetic toxicology

The Dedon Lab has had a long-standing interest in chemical etiology of human disease, with a focus on the role of inflammation and endogenous DNA damage as drivers of carcinogenesis and age-related diseases. We have developed a variety of analytical tools to interrogate genetic toxicology and endogenous molecular damage, including sensitive chromatography-coupled mass spectrometric methods to quantify dozens of different DNA, RNA and protein damage products. This 'omic approach to quantifying molecular damage allows us to interrogate all types of inflammation chemistry occurring in a tissue, including macrophage-induced oxidative and nitrosative stresses and neutrophil-mediated halogenation chemistry, as well as the indirect damage caused by generation of reactive electrophiles by oxidation of sugars and lipids.

Research in the Dedon Lab is broadly organized into three major areas:

  • The genetic toxicology of inflammation and aging
  • The epitranscriptome in infectious disease and cancer
  • The epigenetics of the human gut microbiome and microbial pathogens

tRNA image: Yikrazuul CC BY-SA 3.0 from Widimedia Commons
DNA image: Zephyris at the English language Wikipedia GFDL

Lab Safety First! Accessibility@mit

- July 2024: The Dedon Lab wishes a fond farewell to Boon Chong Goh as he sets off on the big adventure of launching his own company, ArrowBiome. Wishing him all success!

- June 2024: Pete Dedon was interviewed by Rick Woychik, the Director of NIEHS, where he spoke about the microbiome's influence on human health.

-21 February 2024: The Dedon Lab welcomes Chemistry graduate student Maysa Illamanova!

-31 October 2023: The United States Patent and Trademark Office issued US Patent No. 11,802,311 for work pioneered in the Dedon Lab entitled METHODS OF QUANTIFYING RNA AND DNA VARIANTS THROUGH SEQUENCING EMPLOYING PHOSPHOROTHIOATES.

-23 October 2023: Pete Dedon spoke at the MIT Aging Brain Initiative Symposium about the pathology of amyloid plaques and tau protein fibrillary tangles in neurodegenerative diseases, and how aberrant modifications of transfer RNA (tRNA) and silent mutations of codons could play a role.

-20 August 2023: The Dedon Lab welcomes BE graduate student Abby McShane!

-11 Jul 2023: Wei Lin’s discovery of a new stress signaling system that enables bacterial cells to adapt and protect themselves against the immune system and certain antibiotics as published in Nature Communications. Covered at News-Medical.net and at Medical Channel Asia.

-17 Jun 2022: Principal Research Scientist Boon Chong Goh made a presentation on Antimicrobial Resistance at TEDxPSBAAcademy.

-8 Jun 2023: Shane Byrne and the Proteomax team were chosen from among 600 entrants for the final-three pitch in the $1M Temasek Liveability Challenge in Singapore. See Shane’s formal pitch at the Liveability Challenge Grand Finale, and watch his brief elevator pitch.

-23 May 2023: In a publication in JAC-Antimicrobial Resistance, Rifaximin potentiates clarithromycin against Mycobacterium abscessus in vitro and in zebrafish, Dr. Boon Chong Goh in the Dedon Lab discovered a combination of FDA-approved antibiotics that synergizes to kill antibiotic-resistant Mycobacterium abscessus infections. Macrolide antibiotics such as clarithromycin are the cornerstone of treatment for these non-tuberculous mycobacterial infections (NTM), but antibiotic resistance is increasing rapidly, leading to incurable pulmonary infections. The newly discovered antibiotic combination offers hope for treating drug-resistant NTMs and clinical development is underway. The story was covered in a Channel News Asia (CNA) live studio interview with lead author, Dr. Boon Chong Goh, and it also appeared in MIT News, Medical Xpress, Pharmiweb, Pharma Advancement, World Pharma Today, and BioSpectrum Asia.

-31 Jan 2023: Pete Dedon was elected as a fellow of the American Association for the Advancement of Science.

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