Research with a destination

IBRI researchers leverage induced pluripotent stem cell (iPSC) technology to generate cell lines that can be differentiated into multiple human cell types, including microglia, neurons, Schwann cells and other neural lineages, as well as beta cells, macrophages, osteoblasts, cardiomyocytes and many other cell types. These cells are used to understand genetic diseases, validate therapeutic targets and benchmark novel drug candidates.

IBRI scientists also integrate iPSC-derived cells into microphysiological systems (MPS) and organoid platforms that recreate multi-organ interactions. These include brain organoids for the study of neurodegenerative and other CNS diseases, as well as models that evaluate transport and other drug interactions across the blood-brain barrier.

This approach provides powerful tools for disease modeling, therapeutic discovery, and precision medicine by offering more predictive, relevant models than traditional animal systems, which often fail to capture important aspects of human disease. As these microphysiological systems are increasingly adopted by pharmaceutical companies and regulatory agencies to improve drug absorption, metabolism and toxicity predictions, they are becoming increasingly useful in the development process. Longer-term, these platforms hold promise for reducing reliance on animal models, accelerating drug development and improving the success rate of clinical trials.

IBRI researchers combine cutting-edge computational methods with the latest medicinal chemistry approaches to create novel compounds that are designed to realize the therapeutic potential of new biological discoveries made by researchers within the institute and by our collaborators. Our teams initially use virtual screening to identify a set of ligand molecules with potential as drug development candidates. More detailed analyses of the interactions between these ligands and their biological targets are then conducted using strategies that incorporate molecular dynamics calculations, pharmacophore modeling, generative AI and other computational approaches. These in silico analyses then produce molecular scaffolds that can be refined by IBRI’s medicinal chemists into drug-like compounds for preclinical and clinical development.

Data created during this process is used to continuously refine our computational models for analyzing molecular interactions, with the goal of translating research discoveries into novel treatments that are potent, selective and able to reach their targets by the desired route of administration.

Generally, protein therapeutics must maintain their stability and bind specifically and selectively to their intended target. IBRI researchers use techniques such as biolayer interferometry to evaluate the binding of different antibodies to proteins. Techniques such as differential scanning fluorimetry and dynamic light scattering address questions about stability and other properties. These resources are supplemented by collaborators at partner institutions who have capabilities in structural studies using techniques such as cryogenic electron microscopy and nuclear magnetic resonance.