(12ab) Engineering Intelligently Designed Nano- and Microparticles to Control Interactions with the Immune System

Nano- and micro-particulate carriers enable the site-specific delivery for controlled biological responses and can harness the intrinsic pathways by which the body responds to natural invaders. These particles are in size range which naturally associates with many innate immune cells, including antigen presenting cells (APCs), and can interface with these cells to deliver a stimulus. Through controlled design properties, engineered nano- and microparticle drug delivery vehicles have the potential to expand the breadth of many therapeutic approaches, impacting immunological outcomes through cell-specific targeted delivery. However, in many applications, such as mucosal vaccines or controlled-release lung depots, optimal particle properties have not yet been identified. Many particle design considerations have been established for systemic intravenous administration to create long-circulating drug delivery vehicles, yet less is known about particle design parameters critical to interfacing with and directing the immune system.

My research to date has focused on filling in these gaps by designing particles to engineer a controlled response with the immune system. Importantly, this research has ranged from particle synthesis, functionalization, and characterization to extensive evaluations in a range of in vitro and in vivo models. During my PhD, I investigated the role of particle properties to increase local residence times and alter the cellular fate of nano- and microparticles delivered to the lung. In these works, particle association in lung APC populations was characterized as a function of particle parameters, including size, surface charge, shape, and surface chemistry. This work demonstrated the potential use of cationic nanoparticles as pulmonary mucosal vaccines, which were shown to produce superior local and systemic immune responses, as well as PEGylated formulations to extend residence times in the airways. Research during my postdoc has focused on designing particle therapeutics, again at the interface between particle formulations and interactions with blood cells. This work has evaluated particle properties of size, shape, modulus, and surface chemistry to understand interactions with blood cells and inflamed endothelial cells under physiological blood flow, specifically during inflammatory events. Additional projects funded independently under the UM Presidentâ??s Postdoctoral Fellowship have evaluated controlled presentation of toll-like-receptor (TLR) adjuvant molecules on the surface of particle carriers to direct Th1 immune stimulation. Combined, these works demonstrate a potential for rationally designed particle therapeutics to interface with the immune system. Future research will continue to evaluate particle design features on controlled immune interactions, especially in non-intravenous routes of administration, towards the development of novel treatments for vaccinations, cancer, inflammation, and allergy.

Teaching Interests:

Transport, Mass and Energy Balances, Heat and Mass Transfer. I have experience guest lecturing for undergraduate level Chemical Process Analysis through the Mentored Teaching Award at North Carolina State University, as well as Heat and Mass Transfer at the University of Michigan.