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1. Immunocompetent human tissue models for cancer immunoregulation
Primary glioblastoma is the most aggressive brain cancer, with a five-year survival rate of about 5%. Despite treatment advances, current therapies do not significantly improve outcomes. This research aims to uncover pathways glioblastoma uses to evade immune surveillance, focusing on its interactions with microglia. We will identify microglial suppression mechanisms to create new therapeutic targets and enhance immune strategies against glioblastoma.
Goals:
• Develop immunocompetent cerebral organoid models.
• Investigate microglia–glioblastoma interactions.
• Engineer microglia with enhanced immunoregulatory function.
Goals:
• Develop engineered hPSC-macrophage-based immunotherapies
• Engineer hPSC-macrophages with target cell specificity.
• Enhance sensitivity and selectivity of synthetic gene circuits of cell therapies
2. Immunoengineering strategies for enhancing cell-based immunotherapies
Cell-based cancer immunotherapies face challenges from inadequate immune cell infiltration and an immunosuppressive microenvironment. Issues like limited chemotactic potential, exhaustion, and tumor cell evasion hinder engineered T cell strategies. This research investigates engineered macrophage therapy using hPSCs to boost tumor infiltration, enhance cancer cell phagocytosis, and improve the tumor-immune microenvironment for greater therapeutic efficacy.
3. SynBio approaches for advanced drug delivery
Precise spatiotemporal control of biomolecule presentation is a significant challenge in drug delivery. This research aims to employ synthetic biology and liposomal technologies to create a highly programmable bioengineered platform for advanced drug delivery applications by utilizing recombinant optogenetic transmembrane pumps and subsequent light-activation.
Goal:
• Incorporate optogenetic pumps into liposomes with an orientation bias for controlled transport.
Goals
•Develop immunocompetent kidney organoid models.
• Investigate immune interactions in kidney disease.
• Improve drug screening and mechanistic studies of renal pathology.
4. Immunocompetent human tissue models for regenerative medicine
Chronic kidney disease (CKD) affects about 36 million in the U.S. and over 850 million globally, causing significant morbidity, mortality, and healthcare costs. Despite its prevalence, curative treatments are largely absent due to inadequate in vitro models that fail to capture immune interactions. This research develops immunocompetent kidney organoids to better study autoimmune diseases, drug toxicity, and therapies. It enhances disease modeling and advances precision medicine for renal disorders by incorporating essential immune components.
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