Research

• Structural and Functional Modeling of HIV Drug Metabolism in the Infant Liver: Using both in vitro methods and novel iPS cell culture approaches, we are obtaining the kinetic (K_m, V_max, CL_int) and structural (X-ray crystal structure) parameters that define metabolism of HIV inhibitors by CYP3A7, a neonatal specific CYP isoform.
• Computational Modeling of HIV Drug Metabolism and Transport in the Infant Liver: In order to be able to accurately predict drug metabolism and disposition in the developing infant, we need to have reliable computational tools. To this end, data obtained from the in vitro and cell culture studies is being modeled to obtain the QSAR of CYP3A7 mediated metabolism of HIV inhibitors, and also to build a PBPK model of their disposition using the Simcyp™ software package.
• Development of Micro-organoid Models of the Infant Liver: Creating a 3D cellular microenvironment that accurately mimics the functions of the infant liver is of vital importance to preserve endogenous functions in a relevant model system. Although the liver has been especially challenging due to its notable cellular heterogeneity, the “organ-on-a-chip” technologies have shown promise in mimicking these cellular microenvironments. Currently, the Lampe lab is in the early stages of developing a micro-organoid model of the infant liver that would be compatible with the “organ-on-a-chip” technology that has been exploited with other organ types.