Harnessing biomaterials to study and engineer immune function
Our research combines biomaterials and nanotechnology to 1) understand the interactions between synthetic materials and immune tissues, and 2) design more selective therapeutic vaccines for cancer and autoimmunity. One direction involves direct delivery of degradable polymer depots to lymph nodes, the tissues that control adaptive immunity. Using depots loaded with myelin – the self-antigen attacked in multiple sclerosis – and regulatory or metabolic immune cues, we are able to permanently reverse paralysis in mouse models of multiple sclerosis (MS). This tolerance is myelin-specific, mediated by regulatory T cells, and is achieved with a single injection, even when administered at the peak of established disease. We have also shown these mice exhibit reduced inflammation in the brain, and are able to generate functional responses when challenged with exogenous antigen after recovering from MS. In cancer, we are using this modality to program the local lymph node microenvironment to expand T cells against tumor-associated antigens (e.g., melanoma, neuroblastoma), while maintaining plasticity that confers a highly proliferative phenotype. The goal is to recapitulate the efficacy of adoptive cell therapy, but eliminate the need to isolate, condition, and reinfuse cells to patients. In a second thrust, we have developed a new platform to self-assemble peptide antigens and combinations of toll-like receptor (TLR) ligands. These biomaterials mimic attractive features of nanomaterials (e.g., co-delivery, tunable loading), but are assembled entirely from immune signals. Thus assembly is simple, low energy, and solvent-free, while the density of signals is high relative to systems that require encapsulation in excipients or carriers. Using subcutaneous or intra-dermal injection of these materials, we are programing the levels and combinations of TLR signaling in mouse models of melanoma for cancer vaccination. To apply this idea to tolerance, we have designed assemblies comprised of self-antigens and antagonistic TLR ligands. The motivation for this approach is the discovery that excess TLR signaling plays a strong role in driving human MS and other autoimmune diseases. In cells and mouse models of MS, these materials attenuate TLR signaling to polarize T cells toward regulatory T cells that promote myelin specific-tolerance and eliminate disease. In samples from human MS patients, treatment polarizes myelin-triggered T cell response toward tolerance.
Christopher M. Jewell
Assistant Professor, Fischell Department of Bioengineering
University of Maryland
Dr. Jewell graduated from Lehigh University in 2003 with a B.S. in Chemical Engineering and a B.S. in Molecular Biology . He completed his PhD in Chemical Engineering at the University of Wisconsin - Madison in 2008. Chris then joined the Boston Consulting Group in New York City, where his work focused on consulting for R&D strategy development for global pharmaceutical and biotechnology clients. In 2009 he was awarded a Ragon Postdoctoral Fellowship, training under Dr. Darrell Irvine at MIT, and held a concurrent appointment as a Visiting Scientist in the Division of Vaccine Research at Harvard. In August 2012, Chris established his own lab. Dr. Jewell has published 47 papers and patents, including studies in Cell Reports, ACS Nano, PNAS, Angewandte Chemie, and Nature. Dr. Jewell’s efforts have been recognized by numerous awards for research and education, including selection as a 2016 Cellular and Molecular Bioengineering Young Innovator, and receipt of the NSF CAREER Award, Damon Runyon-Rachleff Innovator Award, Melanoma Research Alliance Young Investigator Award, and Controlled Release Society Postdoctoral Achievement Award. Chris has also appeared in USA Today as a “New Face of Engineering”, and was selected as the state of Maryland’s Outstanding Young Engineer by the Maryland Academy of Science, the state’s highest honor awarded to an engineer under age 36.
Molecular Engineering and Sciences Seminar Series
This weekly seminar brings together students, faculty and invited guests from various disciplines across campus to explore current trends in molecular engineering and nanotechnology. It is a forum for active interdisciplinary discussions. These talks are open to the public and attract a diverse audience of students and faculty.