(2ae) Antibody-Conjugated Polymers and Nanoparticles for Targeted Chemo- and Immuno-Therapies

Cancer remains a prominent cause of death globally, with a consistent rise in new cases and fatalities every year, despite extensive research and advancements in treatment options. The emergence of innovative technologies, particularly in the field of biomedicine, has led to the development of diverse strategies for combating cancer. Nonetheless, these approaches often prove effective only for specific types of cancer or certain patients due to the inherent heterogeneity of the disease. Consequently, future therapies must strive for greater precision in treating various forms of cancer.

In the future, my research will primarily focus on the development of innovative and targeted cancer therapeutics. This encompasses a wide range of approaches, including antibody-targeted therapy and immunotherapy, aimed at effectively treating different types of cancers. Simultaneously, I will also delve into fundamental aspects of chemistry, such as exploring the structure-property relationship, as well as investigating key biological elements like the mechanism of action and signaling pathways. These investigations will serve as a solid foundation to support my research endeavors. The nature of my future research will be highly interdisciplinary, relying on the integration of various branches of knowledge and skillsets. This will encompass fields such as physical organic chemistry, synthetic chemistry, polymer chemistry, physics, bioconjugation, molecular biology, protein engineering, and immunology. By utilizing this multidisciplinary approach, I aim to address long-standing challenges in biomedicine and contribute to the overall improvement of healthcare for society. Specifically, my laboratory will prioritize the following research areas in the pursuit of next-generation therapeutics.

First and foremost, drawing inspiration from the promising targeted therapies of antibody-drug conjugates (ADCs), my research will focus on utilizing antibody-targeted delivery as an efficient strategy for treating various cancers, such as pancreatic cancer and breast cancer. While ADCs have demonstrated significant therapeutic efficacy, their design principles inherently limit their broad application, and several challenges persist. One such challenge is the low drug-to-antibody ratio observed in traditional ADCs, which leads to suboptimal therapeutic effectiveness. Additionally, the limited selection of payloads and their associated high toxicity pose significant hurdles to further drug development. To address these challenges, I will employ a combination of polymer synthesis, protein engineering, and novel conjugation chemistry techniques. Specifically, I will develop antibody polymer conjugates using a site-specific approach to overcome the limitations of traditional ADCs. This novel approach aims to achieve high drug loading, thereby improving the drug-to-antibody ratio, while ensuring high targeting efficiency. By integrating these methodologies, my research seeks to enhance the efficacy and safety profile of targeted cancer therapies, ultimately contributing to the advancement of cancer treatment strategies.

Next, my focus will be on designing a novel targeted nanomedicine strategy for cancer treatment. Nanomedicine holds immense promise as a therapeutic approach and has gained significant attention for its applications in various diseases, particularly cancer. Among the cutting-edge nanotechnologies, lipid nanoparticles or lipid-based assemblies have emerged as highly promising delivery vehicles for biomedicine applications. These lipid particles possess unique properties that enable the loading of diverse drugs, ranging from small molecules to biologics, with distinct physicochemical properties, facilitating efficient drug delivery. However, despite the FDA approval of several lipid-based drugs, achieving cancer-specific targeted delivery remains a significant challenge. Currently, most of these particles passively accumulate in the liver, resulting in minimal effective drug concentrations at the targeted disease sites. Attempts to achieve targeting efficiency through the conjugation of targeting moieties on the particle surface have been unsuccessful. This is primarily due to the short pharmacokinetics of lipid nanoparticles, along with the rapid formation of a protein corona on the particle surface, rendering the conjugated targeting moieties indistinguishable. Addressing this challenge, I aim to develop a method that enables the achievement of targeted lipid nanoparticles with desired surface properties for delivering various therapeutics to combat different diseases. By tackling this issue, my research seeks to overcome the limitations of current lipid-based nanomedicine and enhance the efficacy of targeted drug delivery, particularly in the context of cancer treatment.

Furthermore, I will devote my efforts to developing efficient immunotherapy strategies for cancer treatment by harnessing the power of our own immune system. Current immunotherapy methods, such as immune checkpoint blockade (ICB) and CART cell therapy, primarily focus on activating T cells for combating cancer. However, a significant portion of patients does not respond to these treatments. As an alternative approach, leveraging the innate immune system for cancer treatment holds promise in benefiting a larger population. To achieve this, I will employ a targeted delivery strategy to administer various immune-modulating drugs. By targeting different immune pathways through combination therapy, we aim to achieve robust therapeutic efficacy. This approach recognizes the importance of engaging multiple facets of the immune system to enhance anti-cancer responses. By exploring the potential of targeted immunotherapy, my research aims to expand the treatment options available and improve outcomes for a broader range of cancer patients. Through these efforts, we hope to contribute to the advancement of immunotherapeutic strategies and their application in clinical settings.

In summary, my research interests revolve around cancer therapeutics, encompassing a multidisciplinary approach that integrates knowledge and tools from various disciplines. Through this interdisciplinary perspective, I strive to develop novel strategies for cancer treatment. My ultimate goal is to translate these research findings into effective therapeutic drugs that can be utilized for the benefit of society as a whole. By contributing to the advancement of cancer treatment, I aim to make a meaningful impact on improving patient outcomes and enhancing overall healthcare.

Teaching Interests

As an enthusiastic educator, my primary objective is to cultivate a dynamic and captivating learning environment that inspires students to think critically and nurtures their innate love for acquiring knowledge. I firmly believe that fostering interest serves as an exceptional catalyst for effective learning, as it amplifies students' enthusiasm for exploring new concepts. Moreover, I understand that successful teaching entails a blend of expertise in the subject matter, ingenuity, and an unwavering commitment to student achievement.

Drawing upon my research experiences and diverse skill set, I am thrilled to teach a broad spectrum of courses tailored for both undergraduate and graduate students. These may include general chemistry, polymer chemistry, organic chemistry, biological chemistry, materials chemistry, thermodynamics/kinetics, and nanoscience, among others. Additionally, I have plans to introduce an innovative course titled "Biomaterials for Targeted Therapy" designed for advanced undergraduates and graduate students. This course will delve into the intricacies of designing, synthesizing, and characterizing biomaterials to achieve precise therapies that target specific tissues, cells, or even subcellular organelles. By offering a diverse range of courses and incorporating cutting-edge topics into the curriculum, I aim to equip students with the knowledge and skills necessary to thrive in their academic and professional journeys. My ultimate aim is to empower students to become independent thinkers and problem solvers, capable of making significant contributions to the fields of chemistry, biomaterials, and beyond.