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Vanderbilt-Pittsburgh Resource for Organotypic Models for Predictive Toxicology

Vanderbilt-Pittsburgh Resource for Organotypic Models for Predictive Toxicology
  2. Publications

Publications

  1. Ding T, Lambert L, Aronoff D, Osteen KG, Bruner-Tran KL. Sex-dependent influence of developmental toxicant exposure on Group B Streptococcus mediated preterm birth in a murine model.  Reproductive Sciences (in press)
  2. Bruner-Tran KL, Gnecco, JS, Ding T, Glore DR, Pensabene V, Osteen KG. Exposure to the Environmental Endocrine Disruptor TCDD and Human Reproductive Dysfunction: Translating Lessons from Murine Models.  Reprod Toxicol.  2017 Mar;68:59-71. doi: 10.1016/j.reprotox.2016.07.00

    Findings of Merit: Demonstrated a transgenerational occurrence of several reproductive diseases in mouse model after TCDD exposure and introduction of organ-on-chip model.
  3. Gnecco JS, Pensabene V, Li D, Ding T, Hui E, Bruner-Tran KL, Osteen KG. Compartmentalized culture of perivascular stroma and endothelial cells in amicrofluidic model of the human endometrium.  Ann Biomed Eng (2017) 45: 1758. https://doi.org/10.1007/s10439-017-1797-5

    Findings of Merit    : Long term in vitro co-culture of human endometrial stromal and endothelial cells in a dual chamber microfluidic device used to simulate temporal hormone changes during a 28-day menstrual cycle shows successful differentiation, steroid sensitivity for up to 4 weeks.
  4. Gnecco JS, Anders AP, Cliffel D, Pensabene V, Osteen KG, Aronoff DM. (2017) “Instrumenting a Fetal Membrane on a Chip as Emerging Technology for Preterm Birth Research”. Current Pharmaceutical Design, 23 (46). ISSN 1381-6128

    Findings of Merit    : Review of emerging microfabrication technologies for in vitro gestational membrane models, histological characterization of the fetal membrane microenvironment for scaling and recapitulation of functional components of the human fetal membrane, application of the “Instrumented Fetal Membrane on a Chip” (IFMOC) design for toxicological and pharmacological screening, as well as personalized medicine.

  5. Soto-Gutierrez A, Gough A, Vernetti LA, Taylor DL, Monga SP. “Pre-Clinical and Clinical Investigations of Metabolic Zonation in Liver Diseases: The Potential of Microphysiology Systems” Experimental Biology and Medicine 2017; 0: 1–12. DOI: 10.1177/1535370217707731

    Findings     of Merit: Review of metabolic zoning to regulate hepatocyte adaptation and repair, effects of pathological organ-specific microenvironment on zonation and cell signaling, and discussion of new human microphysiological platforms to aid understanding of liver disease progression, diagnosis, and therapies.

  6. Vernetti LA, Gough A, Baetz N, Blutt S, Broughman JR, Brown JA, Foulke-Abel J, Hasan N, In J, Kelly E, Kovbasnjuk O, Repper J, Senutovitch N, Stabb J, Yeung C, Zachos NC, Donowitz M, Estes M, Himmelfarb J, Truskey G, Wikswo JP, Taylor DL. “Functional Coupling of Human Microphysiology Systems: Intestine, Liver, Kidney Proximal Tubule, Blood-Brain Barrier and Skeletal Muscle”, Scientific Reports 7: 42296, Feb 2017. doi:10.1038/srep42296

    Findings of Merit: Sequential transfer of media w/ terfenadine, trimethylamine, and vitamin D between gut, liver, and kidney organotypic culture models demonstrating absorption, metabolism and clearance along with exposure of neurovascular and skeletal muscle models. Data showed organ-specific processing of compounds consistent w/ clinical data and discovered trimethylamine-N-oxide (TMAO) crosses the blood-brain barrier. 

  7. DoddsJN, May JC, McLean JA. “Investigation of the Complete Suite of the Leucine and Isoleucine Isomers: Toward Prediction of Ion Mobility Separation Capabilities”, Anal. Chem. 89, 952−959, Dec 2016. DOI: 10.1021/acs.analchem.6b04171

    Findings of Merit    : Study to separate isometric mixtures using 11 isomers of C6H13NO2 (m/z 131) via drift tube ion mobility mass spectrometry. Correlation of gas-phase collision cross section (CCS) and resolution enables the development of computational approaches to predict separation of any two compounds with known CCS for ion-mobility instruments w/ well characterized resolving power. A mathematical relationship relating the CCS to resolving power was developed in order to predict the required ion mobility resolving power needed to separate the various isomer classes.

  8. Vernetti LA, Vogt A, Gough A, Taylor DL. Book Chapter: "Evolution of Experimental Models of the Liver to Predict Human Drug Hepatotoxicity and Efficacy". Clinics in  Liver Disease, February 2017, 21: 197-214. doi: 10.1016/j.cld.2016.08.013.
  9. Hutson MS, Leung MCK, Baker NC, Spencer RM, Knudsen TB. “Computational Model of Secondary Palate Fusion and Disruption” Chem. Res. Toxicol. (in press)
    Findings of Merit    : Multi-cellular, agent-based palate model generated using CompuCell3D in order to quantitatively simulate and predict developmental responses to chronic and acute chemical exposures.
  10. Alexander PG, Clark KL, Tuan RS. “Prenatal Exposure to Environmental Factors and Congenital Limb Defects”, Birth Defects Res (Part C) 108:243-273, 2016. Doi: 10.1002/bdrc.21140

    Findings of Merit    : Review article outlining the limitations of currently available 2D limb development models to evaluate prenatal exposure to environmental toxicants, while highlighting the need to develop process-specific 3D cell culture to fill this gap.

  11. Bruner-Tran KL, Gnecco JS, Ding T, Glore TR, Pensabene V, Osteen KG. “Exposure to the environmental endocrine disruptor TCDD and human reproductive dysfunction: Translating lessons from murine models.”, Reprod Toxicol ., 2016 Jul 14. pii: S0890-6238(16)30264-7

    Findings of Merit    : Demonstrated transgenerational occurrence of multiple reproductive diseases linked to endometriosis after TCDD exposure of  adult female mice and introduction of organ-on-chip model to further examine interactions leading to heritable diseases.

  12. Hutson MS, Alexander PG, Allwardt V, Aronoff DM, Bruner-Tran KL, Cliffel DE, Davidson JM, Gough A, Markov DA, McCawley LJ, McKenzie JR, McLean JA, Osteen KG, Pensabene V, Samson PC, Senutovitch NK, Sherrod SD, Shotwell MS, Taylor DL, Tetz LM, Tuan RS, Vernetti LA, WikswoJP. “Organs-on-Chips as Bridges for Predictive Toxicology,” Applied In Vitro Toxicology,  June 2016, 2(2): 97-102. doi:10.1089/aivt.2016.0003

    Findings of Merit    : Invited review article highlighting the ways organotypic culture models (organs-on-chips) can be used to bridge the gap between animal studies and human toxicology, providing a means to delineate adverse outcome pathways and to advance predictive toxicology.

  13. Gough A, Vernetti L, Bergenthal L, Shun Tong Y, Taylor DL. "The Microphysiology Systems Database for Analyzing and Modeling Compound Interactions with Human and Animal Organ Models," Applied In Vitro Toxicology. June 2016, 2(2): 103-117. doi:10.1089/aivt.2016.0011

    Findings of Merit: Development of an internet database to design and validate microphysiological systems (MPS) as predictive of human safety liabilities. The database provides important capabilities for experimental design, data management, and analysis of safety data for a reference sets of compounds combined with human organ model in vitro data. 
  14. Leung MCK, Hutson MS, Seifert AW, Spencer RM, Knudsen TB. "Computational modeling and simulation of genital tubercle development", Reprod Toxicol. 2016 May 11. pii: S0890-6238(16)30111-3. doi:10.1016/j.reprotox.2016.05.005

    Findings of Merit: Developed multicellular agent-based model of genital tubercle in CompuCell3D that shows important morphogenetic properties dependent on SHH, FGF 10 and androgen pathways.

  15. Vernetti LA, Senutovitch N, Boltz R, DeBioasio R, Shun TY, Gough A, Taylor DL. “A human liver microphysiology platform for investigating physiology, drug safety, and disease models” Exp Biol Med (Maywood). 241(1): 101–114, Jan 2016. doi:  10.1177/1535370215592121