Overview and Vision
The immune system underlies the pathophysiology of nearly every disease, yet therapies that modulate immunity for clinical benefit have yet to reach their full potential. Our laboratory works at the interface of materials science and immunobiology to innovate solutions for immunotherapy. We are guided by the principle that the immune system must dictate therapeutic design requirements and we turn to nature for inspiration to engineer highly modular and tunable materials to accomodate these criteria. By bringing together expertise in colloid and surface engineering, advanced polymerization techniques, cell engineering, and drug delivery, we are developing molecularly engineered materials that specifically target and tightly regulate the delivery of immunomodulator drugs to the organs, cells, and intracellular pathways of the immune system. In doing so, we are making substantial process in a number of arenas, including those described below.
Molecularly Engineered Materials for Biomedical Application
Materials are at the core of our research - the ability to engineer diverse materials with tailored and well-defined properties is critical to controlling biological phenomena. Our laboratory specializes in the design of novel bio- and nanomaterials using cutting edge approaches, including controlled free radical polymerization (e.g. RAFT), self-assembling polymer thin films and colloids, and the synthesis and bioconjugation of biomacromolecules. While applications in immunotherapy are a major focus, our advanced materials engineering capabilities offer foundational technologies with applications in the broader areas of tissue engineering, drug deliver, diagnostics, and cell-based therapy. We welcome collaborations in these and other areas!
Intracellular Delivery of Antigens and Molecular Adjuvants
Cells of the immune system employ a network of molecular sensors and actuators to detect invading pathogens or pathologic tissue and use resultant cues to mount an immune responses. Basic studies of these mechanisms reveal a complex dependence on the spatial organization and intracellular distribution of antigens and immunomodulatory molecules. Therefore, directing exogenously administered antigens and immunomodulatory adjuvants to the appropriate intracellular compartments in precisely defined quantities is critical to more effective vaccines and immunotherapies.
Current delivery technologies provide limited control over intracellular localization cargo, and are consequently unable to engage the entire intracellular repertoire of immunomodulatory targets. We are engineering nanoparticle based delivery systems that tightly regulate the distribution of antigens and molecular adjuvants between intracellular compartments. Combined with research focused on understanding how the intracellular distribution and trafficking of immunotherapeutics influences inflammatory and immune responses, this work is leading to the design of multimodal, tunable delivery platforms for unique drug combinations that engage multible and diverse immune signaling pathways. By eliciting more highly defined and tailored immune responses, these foundational technologies are enabling diverse applications in many diseases.
Engineering (and Re-Engineering) of Vaccine Colloids and Surfaces:
Colloids and surfaces have played a long standing role in our ability to engineer immunity - aluminum salt, or alum, has been used as a vaccine adjuvant for over 80 years, emulsified oil particles have improved the efficacy of flu vaccines in the elderly population, and microneedle patches are emerging as a better way to deliver vaccines. Using innovative polymer and interfacial engineering approaches, we are integrating new functionalities and biological activities into many existing materials used in vaccine delivery (e.g., polymeric particles, liposomes, emulsions). Additionally, we are devloping novel particles and thin ilms for augmenting immune responses and using them in entirely new and unconventional ways.
Cancer immunotherapy harnesses the intrinsic ability of the immune system to search for and specifically destroy malignant cells. Despite enormous potential, many immunotherapeutic approaches have provided only modest clinical benefit due to a limited capacity to elicit robust anti-tumor responses and overcome immunosupressive forces used by tumors to escape detection. We are addressing these challenges using a multi-faceted approach unified by theraputic strategies that confer spatial and temporal control over the delivery of coordinated immunoregulatory cues to dpecific immune cells. First, we are developing a new generation of cancers vaccines based on pH-responsive nanoparticles that enable dual delivery of tumor antigens and diverse immunostimulatory adjuvants. By combining antigen presentation and direct cellular immune responses through controlled activation of innate immune pathways. Second, we are engineering nanoscale drug delivery systems for local modulation of the immunosupressive tumor microenvironment. Finally, we are developing innovated approaches for targeting imunomodulatory agents to specific immune cell types and leveraging these approaches to enhance penetration and accumulation of drugs in tumors.
Inflammation and immunity play critical roles in the progression of both type I and type II diabetes, while also limiting the success of pancreatic islet transplantation, a promising diabetes treatment. Our group is contributing to the diabetes challenge in the following ways. First, the foundational drug delivery dechnologies developed in our group are being explored for tolerance induction through combinatorial delivery of islet auto-antigens and immunomodulatory agents. Second, we are working to improve the outcomme of pancreatic islet transplantation through molecularly re-engineering islet cell surfaces with nanostructured materials for controlled release of anti-inflammatory and immunosuprressive drugs.