NanoEngineering and MicroPhysiological Systems

National Institute Of Biomedical Imaging And Bioengineering, Bethesda

Investigators

Abstract

Development of Microfluidic Thyroid Organoid-on-a-chip We are interested in developing a microfluidic model of the thyroid for use in studying chronic thyroid diseases. We have established protocols for generation of thyroid organoids and spheroids from a human thyroid follicular cell line. We have also established a protocol for generation of endothelial cell microvascular networks using primary human thyroid endothelial cells. We have conducted extensive experiments to optimize thyroid follicular organoid and spheroid generation and characterize their functional and physical properties. We are further developing a fluidic device for the end goal of incorporating the thyroid organoids and microvascular networks to enable detailed investigation of cellular interactions in thyroid tissue. Evaluation of Immunomodulatory Properties of Bacterial Extracellular vesicles Extracellular vesicles are small biological nanoparticles that are used as a form of communication for bacterial and mammalian cells. They incorporate proteins and other biological molecules and are exchanged between different cells. We have established protocols for bacterial extracellular vesicle isolation and characterization. We have also extensively evaluated the effects of different storage temperatures on bacterial extracellular vesicle integrity and functionality. In addition, we have initiated proteomic analysis (through the NCI Proteomics Core) to identify bacterial proteins and bacterial extracellular vesicle proteins with high sequence similarity to thyroid protein epitopes. We are expanding these studies through computational methods for identification of potential molecular mimicry between proteins with sequence similarity. We have also developed assays to quantify antibody-extracellular vesicle interactions, and plan to apply these assays to evaluate cross-reactivity between autoantibodies and bacterial extracellular vesicles. Through these efforts, we aim to evaluate the potential role of bacterial extracellular vesicles in thyroid immune responses. Development of a Thyroid Extracellular Matrix Hydrogel for Enhanced Thyroid Cell Culture In collaboration with Dr. Kaitlyn Sadtler (NIBIB Section on Immunoengineering), we are developing a hydrogel derived from thyroid extracellular matrix for use in phenotypic cell culture of thyroid cells. Preliminary decellularization protocols have been established, and experiments for hydrogel synthesis are being initiated. Establishment of Nanoparticle Synthesis and Characterization Capabilities within NIBIB We have established a nanoparticle characterization space with capability for evaluation of nanoparticle size, zeta potential, and concentration through multiple instruments. This can enable direct evaluation of nanoparticle properties immediately after synthesis or biogenesis. We have optimized instrument protocols for characterization of extracellular vesicles.