In my mind, it was still 6:00 am West Coast time as I drank my quad latte and opened my laptop to take notes on the Opening Plenary Session, “Advancing Single Cell Technologies in Toxicology,” by Dr. Namandjé Bumpus. Scientists packed the large auditorium, likely as eager as I was to hear about her work on single cell proteomics and how data on cellular heterogeneity might be incorporated preclinically.
Having read the SOT abstract and her recent paper in Nature Communications on the application of single cell proteomics, I’ll admit that I was expecting a different presentation. Rather than provide an overview of recent advancements in single cell technologies and the application of these technologies, she demonstrated how traditional toxicology methods can be used in conjunction with single cell technology. Her talk, in three vignettes, covered the range of her work over the course of her career.
Dr. Bumpus first presented an overview of P450 metabolism, focusing on CYP2B6 and what makes something a CYP2B6 substrate. She then explained how we can use CYP2B6 substrate analogs to learn about toxicology and molecular pharmacology. Dr. Bumpus used the analogs to assess activation of IRE1α, a protein that alters gene expression as a response to endoplasmic reticulum-based stress signals.
The second section of her talk delved into what is considered a drug metabolizing enzyme and discussed other reactions that are important in xenobiotic metabolism, such as phosphorylation by kinases. Her research investigated which nucleotide kinases are involved in phosphorylation of tenofovir, an antiviral drug that becomes pharmacologically active through two phosphorylation steps. She used siRNA knockdown of candidate kinases to determine which enzymes contribute to metabolism (in a tissue-specific manner). Then, she investigated how genetic variation in these kinases could lead to differences in metabolism of the antiviral medication.
In her third vignette, Dr. Bumpus introduced how single cell proteomics technologies can be used to fill gaps in knowledge regarding protein abundance, understand post-translational modifications, and probe potential heterogeneity in cellular response at the protein level. Her lab pioneered the development of single cell proteomics on ion mobility time-of-flight mass spectrometers. Using this technology, Dr. Bumpus’s group was able to detect kinases in single cells and reveal that there is heterogeneity in response to drug treatment.
Data from single cell studies collected over the last decade have clearly demonstrated that there is heterogeneity in cell-to-cell xenobiotic outcomes. As single cell technologies continue to advance, I hope we see further incorporation of these methodologies into transitional toxicology studies.
This blog reports on the Opening Plenary Session titled “Advancing Single Cell Technologies in Toxicology” that was held during the 2023 SOT Annual Meeting and ToxExpo. An on-demand recording of this session is available for meeting registrants on the SOT Online Planner and SOT Event App.
This blog was prepared by an SOT Reporter and represents the views of the author. SOT Reporters are SOT members who volunteer to write about sessions and events in which they participate during the SOT Annual Meeting and ToxExpo. SOT does not propose or endorse any position by posting this article. If you are interested in participating in the SOT Reporter program in the future, please email SOT Headquarters.
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