Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi-MPS Integration
Our goal in developing Microphysiological Systems (MPS) technology is to provide an improved approach for more predictive preclinical drug discovery via a highly integrated experimental/computational paradigm. Success will require quantitative characterization of MPSs and mechanistic analysis of exp...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2017
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| Online Access: | http://hdl.handle.net/1721.1/107165 https://orcid.org/0000-0001-6975-5047 https://orcid.org/0000-0002-2325-552X https://orcid.org/0000-0002-1801-5548 |
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| author | Large, E. M. Hughes, D. J. Stokes, C. L. Yu, Jiajie Cilfone, Nicholas A. Sarkar, Ujjal Tannenbaum, Steven R Lauffenburger, Douglas A Griffith, Linda G Cirit, Murat Wishnok, John S. |
| author2 | Massachusetts Institute of Technology. Center for Gynepathology Research |
| author_facet | Massachusetts Institute of Technology. Center for Gynepathology Research Large, E. M. Hughes, D. J. Stokes, C. L. Yu, Jiajie Cilfone, Nicholas A. Sarkar, Ujjal Tannenbaum, Steven R Lauffenburger, Douglas A Griffith, Linda G Cirit, Murat Wishnok, John S. |
| author_sort | Large, E. M. |
| collection | MIT |
| description | Our goal in developing Microphysiological Systems (MPS) technology is to provide an improved approach for more predictive preclinical drug discovery via a highly integrated experimental/computational paradigm. Success will require quantitative characterization of MPSs and mechanistic analysis of experimental findings sufficient to translate resulting insights from in vitro to in vivo. We describe herein a systems pharmacology approach to MPS development and utilization that incorporates more mechanistic detail than traditional pharmacokinetic/pharmacodynamic (PK/PD) models. A series of studies illustrates diverse facets of our approach. First, we demonstrate two case studies: a PK data analysis and an inflammation response––focused on a single MPS, the liver/immune MPS. Building on the single MPS modeling, a theoretical investigation of a four-MPS interactome then provides a quantitative way to consider several pharmacological concepts such as absorption, distribution, metabolism, and excretion in the design of multi-MPS interactome operation and experiments. |
| first_indexed | 2024-09-23T09:04:25Z |
| format | Article |
| id | mit-1721.1/107165 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:04:25Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1071652022-09-30T13:16:57Z Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi-MPS Integration Large, E. M. Hughes, D. J. Stokes, C. L. Yu, Jiajie Cilfone, Nicholas A. Sarkar, Ujjal Tannenbaum, Steven R Lauffenburger, Douglas A Griffith, Linda G Cirit, Murat Wishnok, John S. Massachusetts Institute of Technology. Center for Gynepathology Research Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Chemistry Massachusetts Institute of Technology. School of Engineering Yu, Jiajie Cilfone, Nicholas A. Sarkar, Ujjal Wishnok, John S Tannenbaum, Steven R Lauffenburger, Douglas A Griffith, Linda G Cirit, Murat Our goal in developing Microphysiological Systems (MPS) technology is to provide an improved approach for more predictive preclinical drug discovery via a highly integrated experimental/computational paradigm. Success will require quantitative characterization of MPSs and mechanistic analysis of experimental findings sufficient to translate resulting insights from in vitro to in vivo. We describe herein a systems pharmacology approach to MPS development and utilization that incorporates more mechanistic detail than traditional pharmacokinetic/pharmacodynamic (PK/PD) models. A series of studies illustrates diverse facets of our approach. First, we demonstrate two case studies: a PK data analysis and an inflammation response––focused on a single MPS, the liver/immune MPS. Building on the single MPS modeling, a theoretical investigation of a four-MPS interactome then provides a quantitative way to consider several pharmacological concepts such as absorption, distribution, metabolism, and excretion in the design of multi-MPS interactome operation and experiments. United States. Defense Advanced Research Projects Agency. Microphysiological Systems Program (W911NF-12-2-0039) National Institutes of Health (U.S.) Microphysiological Systems Program (4-UH3-TR000496-03) Massachusetts Institute of Technology. Center for Environmental Health Sciences (NIEHS Grant P30-ES002109) 2017-03-02T20:59:46Z 2017-03-02T20:59:46Z 2015-10 Article http://purl.org/eprint/type/JournalArticle 2163-8306 http://hdl.handle.net/1721.1/107165 Yu, J, NA Cilfone, EM Large, U Sarkar, JS Wishnok, SR Tannenbaum, DJ Hughes, et al. “Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi-MPS Integration.” CPT: Pharmacometrics & Systems Pharmacology 4, no. 10 (October 2015): 585–594. © 2017 American Society for Clinical Pharmacology and Therapeutics https://orcid.org/0000-0001-6975-5047 https://orcid.org/0000-0002-2325-552X https://orcid.org/0000-0002-1801-5548 en_US http://dx.doi.org/10.1002/psp4.12010 CPT: Pharmacometrics & Systems Pharmacology Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Nature Publishing Group Nature |
| spellingShingle | Large, E. M. Hughes, D. J. Stokes, C. L. Yu, Jiajie Cilfone, Nicholas A. Sarkar, Ujjal Tannenbaum, Steven R Lauffenburger, Douglas A Griffith, Linda G Cirit, Murat Wishnok, John S. Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi-MPS Integration |
| title | Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi-MPS Integration |
| title_full | Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi-MPS Integration |
| title_fullStr | Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi-MPS Integration |
| title_full_unstemmed | Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi-MPS Integration |
| title_short | Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi-MPS Integration |
| title_sort | quantitative systems pharmacology approaches applied to microphysiological systems mps data interpretation and multi mps integration |
| url | http://hdl.handle.net/1721.1/107165 https://orcid.org/0000-0001-6975-5047 https://orcid.org/0000-0002-2325-552X https://orcid.org/0000-0002-1801-5548 |
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