(4hh) Precision Immunomodulation with Lipid Nanoparticles: Tailoring Local and Systemic Therapies

I am a core faculty leading the immunoengineering group at the Terasaki Institute for Biomedical Innovation (TIBI). Before this appointment, I was a Ph.D. student and postdoctoral fellow at The University of Michigan and the University of Connecticut, respectively. Additionally, I hold an additional Ph.D. in applied chemistry. My research history predominantly centers around designing, synthesizing, and characterizing nanoparticles tailored for biomedical and immune engineering applications. Moving forward, I intend to employ an interdisciplinary approach in developing state-of-the-art nanoparticles for regenerative medicine, immune engineering, and personalized medicine applications. At the core of my research is the aspiration to engineer novel lipid-based nanoparticle (LNP) technologies. I have concentrated my research on creating, developing, and applying diverse LNPs to modulate innate and adaptive immune responses in cancer, inflammatory diseases, and metaflammation. This involved designing LNPs for accurately delivering antigens, drugs, proteins, and other bio-reagents to modulate immune responses on localized and broader scales.

During my Ph.D., I developed various LNPs designed for co-delivering antigens (Ags), adjuvants (Ads), drugs, and lipids to tailor specific immune responses. My research has revealed that, upon systemic injection in mice, these LNPs can effectively travel to lymph nodes and successfully deliver both Ags and Ads. Such targeted delivery has produced strong and specific T-cell responses in cancer and autoimmune diseases.

Also, I produced a comprehensive library of LNPs characterized by their lipid makeup, types of cargo, surface features, and linking methods (chemical linker) for cargo. This LNP collection has been invaluable for studying immune responses initiated by the strategic delivery of specific cargos or bioreagents.

My studies show that the careful design of LNPs, particularly variations in lipid compositions or target peptides, plays a crucial role in amplifying immune reactions. We have delved deep into how LNP designs influence the delivery efficiency and overall performance of novel immunotherapeutic approaches. By precisely analyzing diverse LNP formulas, we unveiled the substantial impact of slight compositional tunning, especially in lipid structures, on immune system engagement and delivery to various cells. The findings from my Ph.D. research were accepted for publication in prestigious journals, including Nano Letters and the Journal of Controlled Releases, among others.

My findings have paved the way for my future research endeavors. I aim to delve deeper into the molecular and cellular understanding of the immune system's modulation mediated by LNPs.

Since joining TIBI as a faculty, I have generated diverse libraries of LNPs, each differing in lipid compositions and cargos. This LNP collection was engineered to probe the immune system and understand the mechanisms of metaflammation, especially in relation to obesity and autoimmune diseases. This extensive LNP library comprises a variety of lipid combinations, ranging from natural lipids, such as cholesterol, to synthetic saturated and unsaturated lipids. This diversity allows me to dissect the specific influences of these lipids on different facets of localized immune reactions.

Furthermore, we explored the immunomodulatory effects of LNPs when introduced locally into adipose tissue, aiming to elucidate the mechanisms of metaflammation and find innovative approaches to treat obesity. Equipped with these insights, my future research will explore the nuanced interplay between localized inflammatory signals and the onset, maintenance, and control of metaflammation, particularly emphasizing the use of LNPs.

Throughout my academic journey, I've contributed to over 50 journal papers in top-tier journals in my domain, including Nano Letters, Advanced Materials, Advanced Functional Materials, Advanced Healthcare Materials, Journal of Controlled Release, and Clinical Cancer Research. Additionally, I hold nine patents, wrote three book chapters, and delivered over 50 presentations at various international conferences and institutions. My work has garnered the attention of researchers across multiple fields, accumulating over 1900 citations with an H-index of 23. I also had the privilege of serving as a guest editor for several esteemed scientific journals.

Research Interests:

I am an immuno-engineer specializing in nanotechnology, keenly interested in studying nanoparticles (NPs), particularly lipid-based nanoparticles (LNPs), to modulate immune responses.

Over the past five years, my research efforts have been dedicated to the synthesis, development, and translation of various types of NPs, focusing on delivering, engineering, and modulating innate and adaptive immune responses in different animal models (from mice to monkeys) with various disease states, including cancer, inflammatory diseases, and metabolic inflammation (metaflammation). The central focus of my research is the interaction between nanotechnology and immunology, aiming to unravel fundamental biological queries that can inform and enhance the design of potent therapeutic strategies. To achieve this, my lab meticulously engineered NPs with diverse compositions and explored their potential biomedical applications toward advancing the use of nanoparticles to tackle various diseases and disorders. My research perfectly blends pharmacy, chemistry, nanotechnology, immunology, engineering, and biology. This distinctive foundation equips me to lead groundbreaking research at the intersection of nanotechnology and immunology. In the following section, I will outline the future direction of my research lab and demonstrate how my expertise in pharmaceutical science, chemistry, NP engineering, and immunology has empowered me to craft novel technological platforms that address critical challenges in treating immunological diseases with NPs.

Teaching interest: I believe that my proven track record in securing funding indicates my potential for future funding as a faculty member. For more details, kindly refer to my C.V.

I bring over a decade of teaching experience from three distinct universities, having served as a lecturer and a teaching assistant. At various universities in different countries, I led several senior-level courses within the chemistry, Pharmacy, Pharmaceutical sciences, or engineering program. Moreover, I taught multiple courses at the University of Michigan's College of Pharmacy. My teaching has consistently been met with positive student feedback, whether as the primary instructor or a supporting faculty member. Given my extensive research and educational background, I am well-equipped to teach various courses in pharmaceutical sciences, pharmacy, medicinal chemistry, chemistry, and biomedical engineering.