Research in the Wang laboratory focuses on pharmaceutical analysis, drug metabolism and pharmacokinetics, biotechnology and drug delivery, as well as drug discovery for parasitic infectious diseases.
First, we develop Mass Spectrometry (MS)-based quantitative proteomic and metabolomic methods to determine absolute concentrations of proteins (e.g., cytochrome P450s [CYPs], FMOs, and membrane transporters) and lipids (e.g., sterols and eicosanoids) in cells, tissues, as well as in hepatic cells-derived exosomes. Then we use these quantitative results to assist physiologically-based pharmacokinetic (PBPK) modeling of therapeutic drugs, PBPK-guided design of microfluidics-based liver-on-a-chip technology, and development of exosomal biomarkers for liver diseases and precision medicine. In addition, quantitative changes in sterol levels are used to understand functional roles of leishmanial sterol biosynthesis enzymes (e.g., CYP5122A1) and mechanisms of resistance of antileishmanial drugs.
Second, we develop novel oral drug delivery strategies by modulating intestinal permeability. Intercellular junction-modulating peptides have been shown to enhance oral bioavailability of drugs with poor permeability. We aim to apply this biotechnology to developing novel oral formulations of drugs to treat leishmaniasis and human African trypanosomiasis.
Third, we develop microfluidics-based organ-on-a-chip biotechnology (e.g., liver-on-a-chip) to better predict pharmacological and toxicological effects of drugs and diets in the human liver. Accurate modeling and prediction of human pharmacokinetics, drug-drug interactions and hepatotoxicity of drugs and diets (e.g., herbs and alcohol) remain challenging and are under active research. Current investigations utilize conventional in vitro cell cultures and in vivo rodent models to recapitulate human liver functions and diseases, e.g., metabolism, absorption-excretion, signaling, and inflammation. Unlike conventional in vitro cell culture methods, microfluidics-based microscale cell culture (cells-on-a-chip) provides a well-controlled system with physiologically realistic parameters that emulates the organ-to-organ network of the human body. A liver-on-a-chip system could provide human-derived cells with a microenvironment resembling the in vivo situation more closely by controlling medium flow, medium-to-cell ratio, and organ-organ interactions. When properly designed, a liver-on-a-chip system may better predict in vivo pharmacological and toxicological effects of drugs and diets in the human liver. In addition, such system could be used to accurately predict PK and drug-drug interactions in humans.