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Biomedical Engineering Research Seminar

Juliane Nguyen, Ph.D.

University of North Carolina at Chapel hill

Abstract

A persistent challenge in therapeutic delivery is ensuring that drugs, cells, and microbes accumulate and persist at
diseased sites long enough to provide substantial therapeutic benefit. In the heart, this limitation has constrained the efficacy of therapeutics, such as nanocarriers and cells, for myocardial infarction. To address this, we developed an in situ crosslinking strategy where each administered dose of therapeutic acts as a capturing surface for subsequent doses, thereby amplifying targetable surface area and creating localized depots. Using this approach, we engineered Zippersomes, mesenchymal stem cell-derived extracellular vesicles decorated with high-affinity heterodimerizing leucine zippers, which demonstrated increased accumulation, prolonged cardiac retention and yielded substantial improvements in heart function and tissue repair. Similarly, we created ZipperCells, mesenchymal stem cells engineered to present zipper proteins, which migrate to damaged tissue, crosslink in situ, and form “living depots” that sustain therapeutic presence and provide robust regenerative benefits. Beyond the heart, a similar challenge arises in the gastrointestinal tract, where therapeutic microbes must compete against trillions of resident bacteria and are rapidly cleared. To address this, we engineered the probiotic yeast Saccharomyces boulardii to bind extracellular matrix proteins enriched at sites of inflammation. This targeted strategy prolonged gut residence, supported robust microbial persistence, and yielded substantial improvements in both inflammatory markers and histological recovery in models of colitis.

Bio

Dr. Juliane Nguyen is Professor and Vice Chair in the Division of Pharmacoengineering and Molecular Pharmaceutics, School of Pharmacy, University of North Carolina at Chapel Hill. She serves as the Director of Graduate Admissions for the DPMP PhD program. Before joining UNC, she earned her PhD from the Philipps-University of Marburg and subsequently completed a postdoctoral fellowship at UCSF, supported by the Deutsche Forschungsgemeinschaft (DFG). Dr. Nguyen leads an interdisciplinary lab to develop innovative and personalized biotherapeutics for cancer, myocardial infarction, colitis, and other diseases by merging cutting-edge molecular engineering with pharmaceutical sciences and bioinformatics. Her work has been published in Nature Communications, Nature Biotechnology, Nature Reviews Bioengineering, Advanced Functional Materials, Biomaterials, Advanced Drug Delivery Reviews, and other key journals. She has led research programs supported by more than $20 million in grant funding. She served as a member of the NIH Drug and Biologic Therapeutic Delivery (DBTD) study section (2021-2025). Additionally, Dr. Nguyen is the Executive Editor of Advanced Drug Delivery Reviews, the Associate Editor of CMBE, and serves on the Editorial Board of the Journal of Controlled Release. Dr. Nguyen has received several prestigious awards, including the NY-STAR faculty award, the UB Exceptional Young Investigator award, the NSF CAREER Award, the Biomedical Engineering Society - CMBE Young Innovator Award, and the AAPS Emerging Leader Award. She was the recipient of the Galenus Guest Professorship at ETH Zurich. Dr. Nguyen was named a Fellow of the Controlled Release Society, a Fellow of the American Institute for Medical and Biological Engineering, and a Fellow of the American Association of Pharmaceutical Scientists.