580 California St., Suite 400
San Francisco, CA, 94104
Key research themes
1. How can patient-derived organoids faithfully recapitulate tumor heterogeneity to improve cancer modeling and personalized treatment?
This theme investigates the capability of patient-derived organoids (PDOs), especially those originating from cancer tissues or circulating tumor cells, to mirror the genetic, phenotypic, and microenvironmental heterogeneity characteristic of primary tumors. Accurately modeling tumor heterogeneity is crucial for understanding mechanisms driving cancer progression, metastasis, and treatment resistance, ultimately facilitating personalized medicine approaches including drug screening and prediction of patient-specific therapeutic response.
Key finding: Cancer organoids generated from patient-derived tumor tissue stably preserve genetic, proteomic, morphological, and pharmacotypic features of the parental tumor, including intra- and intertumoral heterogeneity. The study... Read more
Key finding: Circulating tumor cells (CTCs) isolated from patient blood can be cultured into organoids that maintain tumor heterogeneity and drug-resistance phenotypes, providing a minimally invasive 'liquid biopsy' model. This enables... Read more
Key finding: Systematic evidence from multiple cancer types confirms that cancer organoids derived from patient tumors retain intratumoral heterogeneity and tumor clonal hierarchy, allowing them to predict clinical drug response with high... Read more
Key finding: Neuroblastoma PDOs preserve the histological architecture, patient-specific chromosomal aberrations (e.g., MYCN amplification, 1p and 11q deletions), and intratumoral heterogeneity of the originating high-risk tumors. This... Read more
2. What advances in organoid culture systems enable faithful in vitro modeling of organ-specific tissues and their cellular interactions?
This theme addresses the technological and methodological progress in establishing patient-derived organoids that recapitulate organ physiology, including cellular composition and cell-cell and cell-matrix interactions. It explores innovative culture media formulations, extracellular matrix substitutes, incorporation of immune components, and genomic engineering techniques that enhance organoid stability, maturation, and functional relevance to native tissues. Such advances are vital for leveraging organoids in basic biology, regenerative medicine, and disease modeling.
Key finding: Developed a fully defined, serum-free culture medium that supports growth of both luminal and basal prostate epithelial lineages and advanced prostate cancers in organoids. Their protocol achieves ~1-2% plating efficiency... Read more
Key finding: Established human intestinal immuno-organoids (IIOs) by co-culturing epithelial organoids with autologous tissue-resident memory T (T_RM) cells that integrate stably within the epithelium. This system recapitulates in vivo... Read more
Key finding: Developed 'Organoid Easytag', a genetic engineering platform combining CRISPR-Cas9 mediated homology-directed repair with flow cytometry-based enrichment to efficiently edit gene loci in human tissue-derived organoids.... Read more
Key finding: Reviewed how organoids derived from pluripotent or adult stem cells self-organize into multi-lineage 3D structures that preserve complex cell-cell and cell-matrix interactions seen in native tissues. The work highlights that... Read more
Key finding: Demonstrated that a novel, defined collagen-based extracellular matrix substitute supports the growth, morphology, and marker expression of mouse and human gastrointestinal organoids equivalently to Matrigel. Moreover,... Read more
3. How are patient-derived organoids being developed and standardized to advance regenerative medicine and personalized therapeutic applications?
This theme focuses on the translation of organoid technology from research to clinical and therapeutic contexts, emphasizing protocols for large-scale, GMP-compliant organoid production, biobanking, gene editing, and disease modeling from various tissues. These developments address scalability, reproducibility, ethical considerations, and functional maturation necessary to realize organoids as tools for regenerative medicine, drug discovery, and precision oncology.
Key finding: Established a Good Manufacturing Practice (GMP)-compatible and scalable protocol for isolation, expansion, and cryopreservation of undifferentiated human pancreas organoids from clinical-grade donor tissue without enzymatic... Read more
Key finding: Reviewed the utility of hiPSC-derived organoids as versatile in vitro models for simulating human organogenesis, disease states, and personalized drug responses. Highlighted the integration of gene editing and emerging... Read more
Key finding: Produced liver organoid-like structures in vitro by co-culturing genetically engineered adult human liver cells (hepatocytes, liver sinusoidal endothelial cells, and mesenchymal stem cells) on Matrigel. These organoids... Read more
Key finding: Provided a comprehensive framework linking stem cell biology, tissue self-organization, and engineering approaches to generate 3D organoids from pluripotent and adult stem cells for hepatic, biliary, and pancreatic tissues.... Read more
Key finding: Identified emergent ethical issues specific to organoid biobanking, including the moral and legal status of organoids, donor consent challenges, governance models, and commercialization concerns. The paper stresses the need... Read more