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The role of exogenous and endogenous factors that contribute to the exposome, which can give rise to DNA damage in the form of adducts [image created through BioRender].
Toxicological journey to a better understanding of DNA damage and repair
Toxicological journey to a better understanding of DNA damage and repair
DNA is constantly under stress and exposed to harmful environmental, as well as internal, factors that can pose a threat to the overall stability and function. Evolution has led to repair pathways like BER, NER, and MMR to compensate for DNA damage entities such as DNA adducts. One of the ways DNA adducts can be further studies relies on urinary adductomics, which provides a noninvasive technique to build a connection between certain classes of DNA adducts and repair pathways in the cell.
Contact Us
Contact Us
Find more information about our research below. If you're interested on joining us, see here.
Use of urinary DNA adductomics to dissect the substrates and pathways of DNA repair
Use of urinary DNA adductomics to dissect the substrates and pathways of DNA repair
This project aims to determine the contributions of BER, NER, and the dNTP pool to the urinary DNA adductome for representative expected and unexpected adducts, via repair deficient mouse models.
Understanding the origins of the mutational landscape in cancer
Understanding the origins of the mutational landscape in cancer
This project aims to investigate the relationship between the adductome and the mutational landscape using emerging techniques in adductomics, nanopore sequencing, and single-molecule duplex sequencing.
Influence of bacteria on host genome instability
Influence of bacteria on host genome instability
We recently discovered that bacteria can modulate the DNA damage response, and induce oxidative stress in host organisms; this project aims to understand how.
Understanding the molecular basis of ovarian cancer
Understanding the molecular basis of ovarian cancer
Based upon some unpublished novel findings, this project aims to better understand why some tumors develop chemoresistance, and how we can overcome this.
Adductome library characterization using machine learning
Adductome library characterization using machine learning
With the rapidly evolving world of technology, this project aims to combine machine learning with reference adductomes to distinguish unique patterns in nucleic acid adduct profiles with relation to toxic exposures for future application.
Assays and approaches
Assays and approaches
Our lab encourages the development and pursuit of advancement. We are always trying to find new ways to better our scientific approaches and ultimately make strides in our fields of research. Below you'll find some our experimental approaches that have been modified by our past and current lab members that have now been officially adopted by our lab for future members. Feel free to reach out to our lab members for more information on our protocols!
High Throughput Comet Assay
High Throughput Comet Assay
Cells are continually exposed to endogenous and exogenous environmental factors, which can lead to DNA damage. Single-cell gel electrophoresis ( the comet assay) is one of the most common methods used to investigate DNA damage and repair (i.e BER, NER, crosslinks, etc.).
See our recent development of a high-throughput variant of the comet assay:
Ji, Y., Karbaschi, M., Abdulwahed, A., Quinete, N. S., Evans, M. D., Cooke, M. S. 2022. A High-Throughput Comet Assay Approach for Assessing Cellular DNA Damage. e63559
Urinary DNA Adductomics
Urinary DNA Adductomics
The exposome represents the totality of endogenous and exogenous exposures across the lifespan. These exposures may result in DNA and RNA damage, in the form of adducts, which is a key factor in the etiology of a variety of human diseases, including cancer. Following repair, nucleic acid adducts are excreted into the urine, making urine an ideal, non-invasive matrix in which to study the whole-body nucleic acid adductome (the totality of nucleic acid adducts). Our lab has developed a method using a combination of ENV+ coupled with PHE, which we show to have provided the best retention of a cocktail of 20 nucleic acid adduct standards. An untargeted high resolution mass spectrometry approach incorporating FeatureHunter 1.3 software was used to demonstrate the ability of this SPE method to successfully recover endogenous urinary nucleic acid adducts in addition to those represented by the cocktail of isotopically labeled standards.
To find out more, see our published methods here:
Keidel, A., Virzi, J., Deloso, L., Möller, C., Chaput, D., Evans-Nguyen, T., Chang, Y. J., Chao, M. R., Hu, C. W., & Cooke, M. S. (2025). Development of an Optimized Two-Step Solid-Phase Extraction Method for Urinary Nucleic Acid Adductomics. Biomolecules, 15(4), 594.
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