The kidney proximal tubule is responsible for the clearance of many drugs and toxins; this role also renders it highly vulnerable to injury. We have used a dual-channel vascularized proximal tubule epithelial cell microphysiologic system (MPS) to model the OAT1/3 mediated renal clearance of compounds including para-aminohippurate and morphine/morphine metabolites and successfully used MPS in vitro parameters to predict human renal clearance. In addition, have also identified a multi-step mechanism of Ochratoxin A nephrotoxicity involving OATs, cytochrome P450s, and GSTs using kidney MPS technology.

Availability of human primary cell-based 3D human small intestinal microtissues that recapitulate structural, efflux and influx transporters, and show functional mimicry with the in vivo counterpart is critical to obtain predictive and reproducible in vitro testing tool for drug development. An in vitro intestinal tissue model that expresses the relevant drug transporters and drug metabolizing enzymes, such as ABCB1/MDR1/P-gp, ABCC1/MRP1, ABCC2/MRP2, and ABCG2/BCRP, CYP3A4, CYP2J2, UDP-glucuronosyltransferases, and carboxylesterases will mitigate drug discovery challenges across the pharmaceutical industry and advance screening of xenobiotic compounds intended for oral administration. These 3D human gut models will also bridge the gap in preclinical testing by providing a more predictive in vitro drug testing platform.

The placenta is an important regulator of fetal exposure to chemicals. We present a novel microengineered biomimetic platform to investigate the maternal-to-fetal transfer of heavy metals in the human placenta with focus on the role of the BCRP/ABCG2 transporter.