Department of Biomedical Engineering
National University of Singapore
The TTE group leverages bioengineering tools to engineer in vitro and ex vivo tumors for personalized drug testing
Every patient’s cancer is unique. Two people with the same cancer who have the same age, gender, height, weight, and ethnicity, and who have similar medical histories, almost surely have two very different cancers biologically. Hence, there is no guarantee that the drug or drugs administered based on cohort response will work for that specific patient.
What if we could make copies of patient tumors in vitro to identify effective therapies for the patient through drug testing?
We adopt an interdisciplinary approach, interfacing with clinicians and the industry, to develop platforms to reconstruct patient tumors using organoid cultures, or to maintain patient-derived tumor explants. We leverage advanced techniques, including single-cell and spatial technologies, to characterize our models. We validate the developed platforms using in vivo evaluation and clinical correlation, where possible.
Research Directions
Developing Organoid-Based Cultures Incorporating Stromal Heterogeneity
We leverage biomaterials engineering strategies and in-depth knowledge of cancer biology and immunology to reconstruct patient tumors, combining patient-derived cancer cells with stromal cells to recapitulate tumor-stromal interactions in the tumor microenvironment.
Using advanced imaging and molecular methods, we also focus on mechanistic studies to elucidate the role of stromal heterogeneity on cancer progression and patient drug response; we have a particular interest in understanding how different CAF and TAM subpopulations influence immunotherapy resistance.
Preserving Patient-Derived Tumor Explants Ex Vivo
Using bioengineering tools, we seek to enhance the preservation of patient-derived tumor explants ex vivo for personalized medicine. Spanning different cancer types, we have developed a platform to better maintain these explants compared to conventional culture systems, preserving the entire tumor microenvironment including fibroblasts and various immune cell populations.
Recreating the 3D Tumor Microenvironment
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Modeling Ewing Sarcoma Tumors in vitro with 3D scaffolds (PNAS)
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Three-dimensional (3D) culture of bone-derived human 786-O renal cell carcinoma retains relevant clinical characteristics of bone metastases (Cancer Letters)
Growing Patient-Derived Xenograft Tumors Using 3D Scaffolds
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Hydrogel-based 3D model of patient-derived prostate xenograft tumors suitable for drug screening (Molecular Pharmaceutics)
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Generation of Matched Patient-Derived Xenograft In Vitro-In Vivo Models using 3D Macroporous Hydrogels for the Study of Liver Cancer (Biomaterials)
Recapitulating Cancer-Stromal Interactions with 3D Hydrogels
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A 3D in vitro model of patient-derived prostate cancer xenograft for controlled interrogation of in vivo tumor-stromal interactions (Biomaterials)
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Development of patient-derived colorectal cancer organoid models incorporating cancer-associated fibroblasts (Acta Biomaterialia)
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Hepatocellular carcinoma organoid co-cultures mimic angiocrine crosstalk to generate inflammatory tumor microenvironment (Biomaterials)
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Bioengineered hydrogels recapitulate fibroblast heterogeneity in cancer (Advanced Science)
Preserving Patient-Derived Tumor Explants with Bioengineered Hydrogels
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Bioengineered hydrogels enhance ex vivo preservation of patient-derived tumor explants for drug evaluation (Biomaterials)
Review Articles on Tumor Engineering
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Hydrogels to Engineer the Tumor Microenvironment In Vitro (Biomaterials Science)
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Heralding a New Paradigm in 3D Tumor Modeling (Biomaterials)
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Hot or Cold: Bioengineering Immune Contextures into Patient-Derived In Vitro Tumor Models (Advanced Drug Delivery Reviews)
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Engineering Stromal Heterogeneity in Cancer (Advanced Drug Delivery Reviews)
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Making In Vitro Tumor Models Whole Again (Advanced Healthcare Materials)