Papers by Zachary Stevens
Toxicology Letters, Oct 1, 2018
Journal of Investigative Dermatology, May 1, 2016
Toxicology Letters, Sep 1, 2014
Toxicology Letters, Oct 1, 2017
Purpose: Drug transport and permeability across the small intestine (SMI) is a key parameter for ... more Purpose: Drug transport and permeability across the small intestine (SMI) is a key parameter for determining bioavailability of orally administered drugs. The currently available in vitro models are highly dependent on immortalized cell lines (e.g. Caco-2) and have significant deficiencies for drug development applications. Therefore, we developed an in vitro SMI model (EpiIntestinal TM ) using normal human intestinal cells which closely recapitulates the physiology, 3D tissue architecture, and function of the small intestine for use in pharmaceutical development applications and inflammation.
composed of ciliated cells, mucus producing cells, and Club cells. We have developed a co-culture... more composed of ciliated cells, mucus producing cells, and Club cells. We have developed a co-culture system, using primary airway epithelial cells isolated from cadaveric bronchial rings and either mast cells derived from CD34-selected cord blood cells or eosinophils isolated by negative selection from peripheral blood. Using this system, we have demonstrated that a feed-forward system between epithelial cells and mast cells augments epithelial cell IL33 production.
Journal of Investigative Dermatology, 2016
Toxicology Letters, Oct 1, 2017
In Vitro Cellular & Developmental Biology - Animal
Pharmaceutical research, Jan 23, 2018
The study evaluates the use of new in vitro primary human cell-based organotypic small intestinal... more The study evaluates the use of new in vitro primary human cell-based organotypic small intestinal (SMI) microtissues for predicting intestinal drug absorption and drug-drug interaction. The SMI microtissues were reconstructed using human intestinal fibroblasts and enterocytes cultured on a permeable support. To evaluate the suitability of the intestinal microtissues to model drug absorption, the permeability coefficients across the microtissues were determined for a panel of 11 benchmark drugs with known human absorption and Caco-2 permeability data. Drug-drug interactions were examined using efflux transporter substrates and inhibitors. The 3D-intestinal microtissues recapitulate the structural features and physiological barrier properties of the human small intestine. The microtissues also expressed drug transporters and metabolizing enzymes found on the intestinal wall. Functionally, the SMI microtissues were able to discriminate between low and high permeability drugs and correl...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 28, 2011
Dopaminergic signaling and plasticity are essential to numerous CNS functions and pathologies, in... more Dopaminergic signaling and plasticity are essential to numerous CNS functions and pathologies, including movement, cognition, and addiction. The amphetamine- and cocaine-sensitive dopamine (DA) transporter (DAT) tightly controls extracellular DA concentrations and half-life. DAT function and surface expression are not static but are dynamically modulated by membrane trafficking. We recently demonstrated that the DAT C terminus encodes a PKC-sensitive internalization signal that also suppresses basal DAT endocytosis. However, the cellular machinery governing regulated DAT trafficking is not well defined. In work presented here, we identified the Ras-like GTPase, Rin (for Ras-like in neurons) (Rit2), as a protein that interacts with the DAT C-terminal endocytic signal. Yeast two-hybrid, GST pull down and FRET studies establish that DAT and Rin directly interact, and colocalization studies reveal that DAT/Rin associations occur primarily in lipid raft microdomains. Coimmunoprecipitatio...
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Papers by Zachary Stevens