BME Distinguished Lecturer Series: Designing Nanoparticles to Probe and Cross Biological Barriers to Immunotherapy

ABSTRACT

The Mucosal Associated Immune System Engineering and Lymphatics (MAISEL) Lab’s research integrates nanotechnology, materials science, and tissue engineering with physiology, medicine, and immunology to probe lymphatics and extracellular barriers via novel ex vivo, in vitro models and nanoparticles. We are particularly focused on studying mucosal barriers to the therapeutic path from the mucosal lumen to the downstream lymph nodes and integrating the newly created knowledge to design immune modulatory therapeutic interventions. We have made significant progress in understanding how nanoparticle material properties like surface chemistry, affect their transport across biological barriers including lymphatic vessels and lymph node interstitial tissues, and designing ways to use nanotechnology to study biological barriers and design therapeutics. We have found that surface chemistry modulates the lymphatic transport of nanoparticles: densely coating particles with the hydrophilic polymer polyethylene glycol (PEG) maximizes nanoparticle transport across lymphatic vessels and also affects the mechanisms used by lymphatic endothelial cells to shuttle nanoparticles into the vessel lumen. We have also found that inflammation causes an increase in stiffness in lymph nodes, characterized using our newly developed nanoparticle system in conjunction with multiple particle tracking technology. Finally, we have also explored using an adjuvant immunotherapy to treat the rare lung disease lymphangioleiomyomatosis. Overall, our work may lead improvements in the design of immunotherapies and vaccines, as targeting the lymph nodes via lymphatic vessels has been shown to increase the effectiveness of these therapies.

BIOGRAPHY

Dr. Maisel obtained her BSE in Materials Science and Engineering from the University of Michigan and PhD in Biomedical Engineering from Johns Hopkins University. She completed her postdoctoral training at the University of Chicago in lymphatic and respiratory immunobiology prior to joining the Fischell Department of Bioengineering at the University of Maryland as faculty in 2019. The Mucosal Associated Immune System Engineering and Lymphatics (MAISEL) Lab’s research integrates materials science, immunology, mucosal barrier physiology, and drug delivery to design nanoparticles to take advantage of and study the interface between biological barriers, particularly the lymphatics, interstitial tissue, and mucosal surfaces, and nanoparticles. Dr. Maisel has won several awards, including NSF GRFP and NIH F32 fellowships as a trainee, the American Lung Association Dalsemer Award, LAM Foundation Career Development Award, NSF CAREER Award, and NIH NIGMS Maximizing Investigator Research Award. Her work has led to numerous high- impact publications, particularly in the field of drug delivery and mucosal and lymphatic immunoengineering, and several patents. In addition to her research, Dr. Maisel is actively involved in increasing diversity and inclusion within Biomedical/Bioengineering through her work with BME UNITE, a group of faculty pushing for action in diversity and inclusion efforts throughout the U.S., her lab’s outreach efforts with underserved elementary and middle schools and research toward designing more inclusive lab environments, and her leadership on the recently established MARC T34 program at the University of Maryland.