A novel approach to interrogating the effects of chemical warfare agent exposure using organ-on-a-chip technology and multiomic analysis.
Organ-on-a-chip platforms are utilized in global bioanalytical and toxicological studies as a way to reduce materials and increase throughput as compared to in vivo based experiments. These platforms bridge the infrastructure and regulatory gaps between in vivo animal work and human systems, with mo...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0280883 |
| _version_ | 1797850444613025792 |
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| author | Tyler D P Goralski Conor C Jenkins Daniel J Angelini Jennifer R Horsmon Elizabeth S Dhummakupt Gabrielle M Rizzo Brooke L Simmons Alvin T Liem Pierce A Roth Mark A Karavis Jessica M Hill Jennifer W Sekowski Kyle P Glover |
| author_facet | Tyler D P Goralski Conor C Jenkins Daniel J Angelini Jennifer R Horsmon Elizabeth S Dhummakupt Gabrielle M Rizzo Brooke L Simmons Alvin T Liem Pierce A Roth Mark A Karavis Jessica M Hill Jennifer W Sekowski Kyle P Glover |
| author_sort | Tyler D P Goralski |
| collection | DOAJ |
| description | Organ-on-a-chip platforms are utilized in global bioanalytical and toxicological studies as a way to reduce materials and increase throughput as compared to in vivo based experiments. These platforms bridge the infrastructure and regulatory gaps between in vivo animal work and human systems, with models that exemplify active biological pathways. In conjunction with the advent of increased capabilities associated with next generation sequencing and mass spectrometry based '-omic' technologies, organ-on-a-chip platforms provide an excellent opportunity to investigate the global changes at multiple biological levels, including the transcriptome, proteome and metabolome. When investigated concurrently, a complete profile of cellular and regulatory perturbations can be characterized following treatment with specific agonists. In this study, global effects were observed and analyzed following liver chip exposure to the chemical warfare agent, VX. Even though the primary mechanism of action of VX (i.e. acetylcholinesterase inhibition) is well characterized, recent in vivo studies suggest additional protein binding partners that are implicated in metabolism and cellular energetic pathways. In addition, secondary toxicity associated with peripheral organ systems, especially in human tissues, is not well defined. Our results demonstrate the potential of utilizing an organ-on-a-chip platform as a surrogate system to traditional in vivo studies. This is realized by specifically indicating significant dysregulation of several cellular processes in response to VX exposure including but not limited to amino acid synthesis, drug metabolism, and energetics pathways. |
| first_indexed | 2024-04-09T19:00:21Z |
| format | Article |
| id | doaj.art-8a8c2319428b41aca14db147c503cfed |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-09T19:00:21Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-8a8c2319428b41aca14db147c503cfed2023-04-08T05:32:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01182e028088310.1371/journal.pone.0280883A novel approach to interrogating the effects of chemical warfare agent exposure using organ-on-a-chip technology and multiomic analysis.Tyler D P GoralskiConor C JenkinsDaniel J AngeliniJennifer R HorsmonElizabeth S DhummakuptGabrielle M RizzoBrooke L SimmonsAlvin T LiemPierce A RothMark A KaravisJessica M HillJennifer W SekowskiKyle P GloverOrgan-on-a-chip platforms are utilized in global bioanalytical and toxicological studies as a way to reduce materials and increase throughput as compared to in vivo based experiments. These platforms bridge the infrastructure and regulatory gaps between in vivo animal work and human systems, with models that exemplify active biological pathways. In conjunction with the advent of increased capabilities associated with next generation sequencing and mass spectrometry based '-omic' technologies, organ-on-a-chip platforms provide an excellent opportunity to investigate the global changes at multiple biological levels, including the transcriptome, proteome and metabolome. When investigated concurrently, a complete profile of cellular and regulatory perturbations can be characterized following treatment with specific agonists. In this study, global effects were observed and analyzed following liver chip exposure to the chemical warfare agent, VX. Even though the primary mechanism of action of VX (i.e. acetylcholinesterase inhibition) is well characterized, recent in vivo studies suggest additional protein binding partners that are implicated in metabolism and cellular energetic pathways. In addition, secondary toxicity associated with peripheral organ systems, especially in human tissues, is not well defined. Our results demonstrate the potential of utilizing an organ-on-a-chip platform as a surrogate system to traditional in vivo studies. This is realized by specifically indicating significant dysregulation of several cellular processes in response to VX exposure including but not limited to amino acid synthesis, drug metabolism, and energetics pathways.https://doi.org/10.1371/journal.pone.0280883 |
| spellingShingle | Tyler D P Goralski Conor C Jenkins Daniel J Angelini Jennifer R Horsmon Elizabeth S Dhummakupt Gabrielle M Rizzo Brooke L Simmons Alvin T Liem Pierce A Roth Mark A Karavis Jessica M Hill Jennifer W Sekowski Kyle P Glover A novel approach to interrogating the effects of chemical warfare agent exposure using organ-on-a-chip technology and multiomic analysis. PLoS ONE |
| title | A novel approach to interrogating the effects of chemical warfare agent exposure using organ-on-a-chip technology and multiomic analysis. |
| title_full | A novel approach to interrogating the effects of chemical warfare agent exposure using organ-on-a-chip technology and multiomic analysis. |
| title_fullStr | A novel approach to interrogating the effects of chemical warfare agent exposure using organ-on-a-chip technology and multiomic analysis. |
| title_full_unstemmed | A novel approach to interrogating the effects of chemical warfare agent exposure using organ-on-a-chip technology and multiomic analysis. |
| title_short | A novel approach to interrogating the effects of chemical warfare agent exposure using organ-on-a-chip technology and multiomic analysis. |
| title_sort | novel approach to interrogating the effects of chemical warfare agent exposure using organ on a chip technology and multiomic analysis |
| url | https://doi.org/10.1371/journal.pone.0280883 |
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