Our major research interest is to understand the biology and the function of extracellular vesicles (EVs) both in physiological and pathophysiological conditions. The aim is to develop a novel tool for disease diagnosis and treatment. Currently, we engineer EVs for visualization, monitoring and targeted-delivery of oligonucleotide therapeutics, including non-coding RNAs (microRNAs), DNAs, and CRISPR-Cas9 as well as low-molecular-weight drugs to develop an advanced therapeutic approach. The ultimate goal of our research is to translate basic scientific findings into clinical applications.
Vesicle release from cells or tissues into the extracellular space is an evolutionally conserved process. In recent years, these vesicles collectively termed small Extracellular vesicles (EVs), including exosomes and microvesicles, became increasingly acknowledged as mediators of cell-cell communication. EVs contain a wide range of biomolecules such as proteins, RNAs, and DNAs, which transfer these functional cargos to distant cells or tissues through circulation. Due to their increased stability in circulation, biocompatibility, low immunogenicity and toxicity, EVs are attractive diagnostic markers and delivery systems for therapeutics.
The lab utilizes genetic/cellular engineering tools to investigate EV biology. In particular, we are developing a biological method to engineer EVs as a drug delivery cargo for oligonucleotide therapeutics and small molecular drugs.
Current research projects:
Targeted Therapeutic Delivery for Type 1 Diabetes
One of the major challenges in gene therapy is targeted delivery. Using beta-cell targeting peptide labeled EVs as a delivery cargo of tissue-specific gene expression system, we aim to develop tools to promote beta-cell health and protect them from immune clearance in pancreatic beta cells to treat type 1 diabetes.
EV-mediated microRNA delivery for EGFR positive tumors
MicroRNAs (miRNAs) are small endogenous non-coding RNA molecules that regulate gene expression in diverse biological processes. Some miRNAs can be a potent therapeutic target for a specific type of cancer and a promising therapeutic molecule. Our lab is developing an EV-miRNA mimic/inhibitor delivery system for EGFR positive tumors to study the efficacy of the miRNA treatment.
Development of “therapeutic guide proteins” using an in vivo EV-display screen
The biocompatibility feature of EVs makes an ideal carrier for in vivo targeting. We are developing an in vivo exosome-display screening strategy to select a “guide protein” expressed on the surface of naturally occurring cell-derived vesicles using the combination of scFv library screening and EV engineering.