RESEARCH
The mission of the Immunoengineering Laboratory at Vanderbilt University is to advance discoveries and innovate technologies to improve human health though research at the intersection of molecular engineering and immunology.
Our research philosophy is guided by the fact that the immune system plays an important, if not deterministic, role in virtually every malady, and therefore, we seek to innovate strategies to precisely regulate immunological processes at the tissue, cell, and molecular level offer enormous potential to cure or prevent disease. To accomplish this, we combine molecular engineering tools and principles – spanning polymer chemistry, materials science, nanotechnology, and synthetic biology – with interdisciplinary biological and translational sciences that also leverage strong collaborations with organic chemists, cancer biologists, and immunologists.
FOCUS AREAS
Molecular Engineering
We take a largely “materials agonist” approach to developing new strategies to manipulate or study the immune system. While most of our work has leveraged polymer engineering to innovate carriers for immunomodulatory drugs, we also have expertise and active collaborations in organic synthesis of novel immunomodulators and pro-drugs, protein and antibody engineering, lipid nanoparticles, extracellular vesicles, engineered cells, and biomaterial scaffolds. Armed with a large and diverse toolbox, we are well-equipped to devise innovative strategies for controlled modulation of the immune system.
Cancer Immunotherapy
Immunotherapy has revolutionized the treatment of a growing number of cancers, resulting in complete and durable responses in some patients. Unfortunately, these remarkable outcomes remain relatively infrequent, particularly for some cancer types or patient sub-populations. Over the past decade, our group has been focused on developing new technologies and therapeutics for improving responses to cancer immunotherapy, with an emphasis on breast cancer, melanoma, kidney cancer, and neuroblastoma. We have been particularly focused on harnessing the innate immune system to reprogram tumor immunogenicity through the development of novel drug delivery systems for improving the efficacy, safety, and/or clinical utility of STING and RIG-I agonists as well as nanoparticle delivery systems and immunostimulatory adjuvants for therapeutic cancer vaccines.
Pathogen-Mimetic Vaccines
Cellular immunity is critical for defense against many important pathogens and for productive immunity against cancers. However, most clinically approved vaccines fail to generate robust and durable T cell responses. We are addressing this challenge through the development of pathogen-inspired vaccines that enhance T cell responses to protein, peptide, and mRNA vaccines for cancer and infectious disease. We seek to engineer vaccine platforms capable of enhancing and tuning cellular immunity by controlling the delivery of immunological cues to tissues and cells of the immune system. We have been particularly invested in engineering polymeric nanoparticles that can precisely regulate the intracellular delivery of antigen and adjuvants to defined subcellular compartments (e.g., cell surface, endosome, cytosol) in a manner that optimally shapes T cell responses to treat cancers or prevent respiratory infections.
Technologies to Treat Inflammatory and Autoimmune Diseases
The immune system is a double-edged sword and over or aberrant activation of the immune system can result in autoimmune diseases (e.g., type I diabetes, multiple sclerosis) or chronic inflammation. A newer direction in our group, we are exploring new strategies for inhibiting or reversing inflammatory and autoimmune diseases. In brief, we are developing strategies for localized and tissue-selective blocking of self-DNA sensing, which is involved in a diversity of inflammatory diseases, as well as “reverse vaccines” by designing autoantigens that “hitchhike” on endogenous regulators of peripheral immune tolerance such as serum proteins and extracellular vesicles.
Microenvironmental Influences on the Immune System
Our technological innovations have also enabled our exploration of more fundamental questions about the immune system and how local environmental changes can influence immune cell fate and function. For example, we are investigating how stimulation of local activation of antiviral innate immunity impacts the vascular-immune interface in tumors, how material properties influence pattern recognition pathway signaling, and the effect of fever-range temperature on immune cell function and responses to environmental stimuli.
