Kim Laboratory

Research Projects

1. Proteomics of Tumor Extracellular Matrix

Glioblastoma (GBM) is the most aggressive primary brain tumor, driven by a highly complex tumor microenvironment (TME) that includes an aberrant extracellular matrix (ECM) promoting invasion and therapy resistance. To overcome the limitations of traditional models in capturing this native ECM, we developed glioblastoma organoids (GBOs) from stem cells that self-synthesize their own native matrix. The core of this project involves decellularizing these GBOs to physically decouple the cellular proteins from the ECM, allowing for their individual, comprehensive proteomic analysis. This study aims to define the protein composition and capture the developmental transitions of the native ECM by comparing the proteomic profiles of decellularized GBOs across different sizes. The critical understanding of GBM progression mechanics allows for more informed design of ECM-targeted therapeutics. Moreover, these isolated ECMs can be transformed into functionalized hydrogels for downstream applications in such therapeutics, or for other cell culture techniques.

2. Biomanufacturing of Tumor Organoids

This project introduces a robust, animal-product-free method for biomanufacturing glioblastoma organoids (GBOs), establishing a highly reproducible and scalable in vitro model for studying glioblastoma (GBM), the most lethal primary adult brain tumor. These GBOs grow to a clinically relevant size (1-4 mm) and spontaneously self-assemble to accurately mimic the cellular heterogeneity and development of the tumor microenvironment (TME). Crucially, the exclusion of animal-derived components reveals the inherent biology of glioblastoma stem cells (GSCs), including their transdifferentiation into endothelial cells to form the neurovascular unit (NVU) and the spatial organization of endogenously secreted extracellular matrix (ECM). Ultimately, these GBOs bridge the gap between the complex physiological relevance of animal models and the availability and human translation of 2D systems, offering a significant step toward clinically relevant in vitro systems for translational medicine.

3. Fluid Shear Stress-Derived Extracellular Vesicles in Cancer Metastasis

Metastatic breast cancer remains the second leading cause of women's mortality in the U.S. This project aims to understand the metastatic process by generating extracellular vesicles (EVs) from a highly metastatic breast cancer cell line using a simplified model of physiological blood flow fluid shear stress. EVs carry genetic material capable of altering normal host-cell behavior and are believed to be instrumental in paving the way for metastasis. The study of these shear-stress-derived EVs is crucial for understanding the formation of secondary tumors and the conditioning of the pre-metastatic niche.