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The Nguyen lab is dedicated to translating cutting-edge research into life-changing therapies for patients suffering from cancer, myocardial infarction, colitis, and other diseases. Our interdisciplinary team of experts combines the power of molecular engineering, pharmaceutical sciences, and bioinformatics to develop genetically and molecularly engineered biotherapeutics that are safe, effective, and tailored to the individual needs of each patient.

Our mission is to revolutionize medicine by developing next-generation therapeutics that target diseases at the molecular level, offering hope and improved quality of life to patients and their families. With a relentless focus on translational research and a commitment to the highest standards of scientific excellence, the Nguyen lab is dedicated to making a difference in the lives of patients around the world. Join us in our mission to transform healthcare through innovative biomolecular engineering.

Research Interests

 

 

Developing therapeutics for cardiac repair

Coronary heart disease is a global health crisis, claiming millions of lives every year. When a heart attack occurs, a significant number of cardiomyocytes, the specialized muscle cells responsible for contracting the heart, die and are replaced by non-contractile scar tissue. This can lead to a weakened heart and ultimately, heart failure.

In our lab, we are dedicated to changing the course of heart disease by developing innovative biomaterials that can prevent cell death and reprogram different types of cells into functional cardiomyocytes, effectively repairing damaged cardiac tissue and restoring normal heart function.

Publications:

ZipperCells Exhibit Enhanced Accumulation and Retention at the Site of Myocardial Infarction. N. Jasiewicz, KC Mei, H. M. Oh, P. Chansoria, D. Hendy, E. Bonacquisti, E. Bachelder, K. Ainslie, H. Yin, L. Qian, B.Jensen, J. Nguyen*. Advanced Healthcare Materials, https://onlinelibrary.wiley.com/doi/abs/10.1002/adhm.202201094, November 2022

In Situ-Crosslinked Zippersomes Enhance Cardiac Repair by Increasing Accumulation and Retention. Jasiewicz NE, Mei KC, Oh HM, Bonacquisti EE, Chaudhari A, Byrum C, Jensen BC, Nguyen J*. bioRxiv [Preprint]. 2024 Mar 16:2024.03.14.585030. doi: 10.1101/2024.03.14.585030.

 

Genetically encoded materials – protein-based materials to target tumor-associated macrophages

While current anticancer therapies primarily target cancer cells, the tumor stroma also plays a crucial role in cancer progression. To address this gap in treatment, we have developed a novel drug delivery approach that targets not only tumor cells but also inflammatory cells. Specifically, we developed a delivery platform that utilizes single-chain variable fragment antibodies to inhibit inflammatory monocyte migration to tumors and polarize macrophages towards the tumoricidal M1 phenotype by hijacking the CCL2/CCR2 pathway. This approach capitalizes on the targeting specificity of antibody fragments and exploits CCR2 receptor structure and function to improve therapeutic efficacy.

Our protein delivery approach minimizes carrier-induced toxicity, as the antibody fragments serve both as a delivery vehicle and therapeutic drug. Through this proposal, we synthesized a modular CCR2-targeting system for macrophage polarization to promote macrophage polarization, and inhibit tumor growth and metastasis in a triple-negative breast cancer (TNBC). Our therapeutic is designed to be used in combination with anti-PD-1 blockade and other therapeutics for the potential treatment of cancer.

Publications:

Killing tumor-associated bacteria with a liposomal antibiotic generates neoantigens that induce anti-tumor immune responses.
Wang M, Rousseau B, Qiu K, Huang G, Zhang Y, Su H, Le Bihan-Benjamin C, Khati I, Artz O, Foote MB, Cheng YY, Lee KH, Miao MZ, Sun Y, Bousquet PJ, Hilmi M, Dumas E, Hamy AS, Reyal F, Lin L, Armistead PM, Song W, Vargason A, Arthur JC, Liu Y, Guo J, Zhou X, Nguyen J, He Y, Ting JP, Anselmo AC, Huang L. Nature Biotechnology. 2023 Sep 25. doi: 10.1038/s41587-023-01957-8.

Calreticulin P-domain-derived “Eat-me” peptides for enhancing liposomal uptake in dendritic cells. Mei KC, Thota N, Wei PS, Yi B, Bonacquisti EE, Nguyen J*.
Int J Pharm. 2024 Jan 23;653:123844. doi: 10.1016/j.ijpharm.2024.123844.

M. Deci, M. Liu, J. Gonya, C. Lee, S. Ferguson, T. Li, E. Bonacquisti, and J. Nguyen*Carrier-free CXCR4-targeted Nanoplexes Designed for Polarizing Macrophages to Suppress Tumor Growth. Special Issue: CMBE – Young Innovator, July 2019, https://rdcu.be/bPIx3

 

Live biotherapeutics for the treatment of inflammatory bowel diseases – the power of engineered, probiotic yeast

Inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis, are chronic and debilitating conditions affecting millions of people worldwide. Current therapies offer only limited relief, leaving patients struggling with severe pain, diarrhea, and other symptoms, often leading to hospitalization and surgery.

In our lab, we are developing the next-generation of therapeutics to treat IBD, using the power of engineered, probiotic yeast to create live biotherapeutics that can effectively reduce inflammation and modulate the gut microbiome towards a protective composition. By focusing on locally acting therapeutics, we can provide a more targeted and effective treatment, while minimizing the risk of systemic side-effects.

Our innovative research is driven by a passion for transforming the lives of IBD patients, who have long been underserved by traditional therapies. By harnessing the power of biomolecular engineering and cutting-edge bioinformatics, we are paving the way towards a future where IBD is no longer a source of suffering, but a manageable condition.

News story: https://news.unchealthcare.org/2024/05/researchers-engineer-yeast-to-deliver-drugs-reduce-inflammation-for-possible-inflammatory-bowel-disease-treatment/

Publications:

Targeted delivery of the probiotic Saccharomyces boulardii to the extracellular matrix enhances gut residence time and recovery in murine colitis. M. Heavey, A. Hazelton, Y. Wang, M. Garner, J. Arthur, and Nguyen J*. Nature Communications, 2024 https://www.nature.com/articles/s41467-024-48128-0

Microbe-loaded bioink designed to support therapeutic yeast growth. E. Etter, M. Heavey, M. Errington, J. Nguyen*. Biomater Sci. June 2023 https://pubs.rsc.org/en/content/articlelanding/2023/BM/D3BM00514C

Killing tumor-associated bacteria with a liposomal antibiotic generates neoantigens that induce anti-tumor immune responses.
Wang M, Rousseau B, Qiu K, Huang G, Zhang Y, Su H, Le Bihan-Benjamin C, Khati I, Artz O, Foote MB, Cheng YY, Lee KH, Miao MZ, Sun Y, Bousquet PJ, Hilmi M, Dumas E, Hamy AS, Reyal F, Lin L, Armistead PM, Song W, Vargason A, Arthur JC, Liu Y, Guo J, Zhou X, Nguyen J, He Y, Ting JP, Anselmo AC, Huang L. Nature Biotechnology. 2023 Sep 25. doi: 10.1038/s41587-023-01957-8.

 

Auxetic patches for dynamic organ repair and wound healing

We developed a new translational patch material with advanced properties that could revolutionize the field of bioadhesive materials and patches for surgical procedures and interventions. This new material exhibits instant adhesion to wet tissues, ultra-stretchability, compatibility with rapid photo-projection, and the ability to deliver therapeutics. Through in silico design and screening more than 100 patches, we created next-generation patches that conform to organ mechanics and instantly attach to a broad range of tissues. In vivo studies have demonstrated remarkable wound healing capability, without the need for removal that can cause pain and bleeding. Additionally, we have developed a new single material-based patch for the treatment of lung puncture wounds.

Publications:

Rationally Designed Anisotropic and Auxetic Hydrogel Patches for Adaptation to Dynamic Organs. P. Chansoria, J. Blackwell, E. Etter, E. Bonacquisti, N. Jasiewicz, T. Neal , S.Kamal, J. Hoque, S. Varghese, T. Egan, Juliane Nguyen* Advanced Functional Materials, August 2022 https://onlinelibrary.wiley.com/doi/10.1002/adfm.202207590

P. Chansoria, E. Etter, J. Nguyen*. Regenerating dynamic organs using biomimetic patches. Trends Biotechnol. 2021 Aug 16:S0167-7799(21)00155-4. doi: 10.1016/j.tibtech.2021.07.001

 

Funding:

       NIH NIGMS