Dr. Jewell graduated from Lehigh University with high honors in 2003 with a B.S. in Chemical Engineering and a B.S. in Molecular Biology. He attended graduate school at the University of Wisconsin – Madison, completing his PhD in Chemical Engineering with Professor David Lynn in 2008. From 2009-2012, Dr. Jewell was a postdoctoral fellow in Darrell Irvine’s lab at MIT and held a concurrent appointment as a Visiting Scientist in the Division of Vaccine Research at Harvard. He has published numerous papers, including in leading journals such as ACS Nano, PNAS, Angewandte Chemie, and Nature. Chris teaches biofluid mechanics and supports and active education and outreach program in the community. He is the recipient of numerous award for research education including the NSF CAREER Award, the Damon Runyon-Rachleff Innovation Award, and the Department’s Outstanding Teaching Award. In 2013 Dr. Jewell was selected as the state of Maryland’s Outstanding Young Engineer by the Maryland Academy of Science, the state’s highest professional honor awarded to an engineer under the age of 36.
Grant Title: Lymph Node Delivery of Immunomodulatory Biomaterial Depots for Therapeutic Vaccination
AN UPDATE FROM PROFESSOR JEWELL
Grant Title: “Lymph Node Delivery of Immunomodulatory Biomaterial Depots for Therapeutic Vaccination”
The PhRMA Pharmaceutics Starter Grant had an incredible impact on the Jewell lab and their research capabilities. The studies during the grant allowed establishment of new disease models of both cancer and autoimmunity, and supported preliminary data that ultimately led to more than $2M in funding in these areas. In addition to the financial support, the network fostered by the PhRMA foundation was invaluable in providing advice and development opportunities for Prof. Jewell and his lab members. Many of these were nucleated by interactions at events sponsored by the PhRMA Foundation at meetings such as the AAPS Conference. The grant will have a lasting impact on the Jewell lab’s growth and ability to contribute new knowledge and therapeutics at the interface of engineering and immunology.
Since wrapping up the grant almost two years ago, the lab has been working on several project areas that were nucleated during the award period. The goal of the Jewell Lab is to develop biomaterials that generate immune responses with specific, tunable characteristics. This research is carried out in three thrusts: 1) to understand the interactions between synthetic materials and immune tissues, 2) to design new materials that provide better control over the signaling and function of immunity, and 3) to translate these advances to therapeutic vaccines for cancer and autoimmune disease. One fundamental project seeks to understand how the properties of biomaterials influence the structure and function of lymph nodes – the tissues that coordinate immune response. The lab has also designed an innovative vaccine platform that offers a new level of simplicity and modularity for controlling the signaling and function of T cells in mice. On the translational front, the group has generated data demonstrating reversal of paralysis in mouse models of MS by locally controlling the function of lymph nodes. In the area of cancer, two promising vaccine strategies have been piloted in mouse models of neuroblastoma – an extra-cranial pediatric cancer, as well as in metastatic and non-metastatic melanoma models. The lab’s efforts have also been recognized by Dr. Jewell’s selection as the state’s Outstanding Young Engineering by the Maryland Academy of Sciences, the University of Maryland Research and Scholar Award, and the Bioengineering Department’s 2015 Faculty Teaching Excellence Award.
Dr. Jewell currently supports a talented team of 14 researchers (5 graduate students, 3 postdoctoral scientists, 1 senior technician and lab manager, 5 undergrads) with backgrounds in bioengineering, immunology, chemical engineering, and molecular biology. Dr. Jewell has published five papers since joining the University of Maryland, and a total of 27 papers with 1465 citations (h-index = 18). These papers have included reports in journals such as ACS Nano, Angewandte Chemie, Nature, and PNAS. Dr. Jewell and his team are also working to translate and commercialize their technologies, with a total of six published or filed patent applications, one of which was a finalist for the University of Maryland’s 2014 Invention of the Year.
In the community, Dr. Jewell’s has created a STEM education program with the Wheaton High School Biosciences Magnet and Academy programs. Through this relationship – which underpins the outreach efforts of Dr. Jewell NSF CAREER Proposal – he created a suite of activities to provide STEM exposure and long-term mentoring through design-based lessons, lab visits, and a year-long program in which the magnet students learn about research by preparing a review paper and poster on a topic they chose. The program involves lectures Dr. Jewell presents, expert interviews, writing assignments, and culminates with a poster symposium. A key component is the pairing of each participant with graduate student or postdoc mentors for the year. The program has involved more than 350 high school students and included ~50 graduate students and postdoctoral mentors.
Read more about our work and our lab at jewell.umd.edu.
1. RECENTLY PUBLISHED MANUSCRIPTS
(1) P. Zhang, Y. C. Chiu, L. H. Tostanoski, and C. M. Jewell. “Polyelectrolyte Multilayers Assembled Entirely from Immune Signals on Gold Nanoparticle Templates Promote Antigen-Specific T Cell Response.” ACS Nano 2015, 9, 6465–6477. doi: 10.1021/acsnano.5b02153.
(2) J. M. Gammon, L. H. Tostanoski, A. R. Adapa, Y. C. Chiu, and C. M. Jewell. “Controlled delivery of a metabolic modulator promotes regulatory T cells and restrains autoimmunity.” J Control Release 2015, 210, 169-178. doi:10.1016/j.jconrel.2015.05.277.
(3) J. I. Andorko, K.L. Hess, and C. M. Jewell. “Harnessing the interactions of biomaterials with lymph nodes to direct immunity or tolerance.” AAPS Journal 2015, 17, 323-38. DOI: 10.1208/s12248-014-9708-2.
(4) J. I. Andorko*, L. H. Tostanoski*, E. Solano, M. Mukhamedova, and C. M. Jewell. “Intra- lymph node injection of biodegradable polymer particles.” J. Vis. Exp. 2014, 83, doi:10.3791/50984.
2. EXTERNAL FUNDING SECURED AS A RESULT OF PHRMA SUPPORT
(1) National Multiple Sclerosis Society Research Grant (PI: Jewell) 10/15-10/18 “Harnessing intra-lymph node controlled release to promote myelin-specific tolerance”
(2) Alliance for Cancer Gene Therapy Young Investigator Award (PI: Jewell) 04/15-04/18 “Harnessing intra-lymph node gene therapy to promote anti-tumor immunity”
(3) Damon Runyon Foundation Innovator Award (PI: Jewell) 01/15-01/17 “Harnessing intra-lymph node controlled release to study and enhance tumor immunity”
(4) NSF CAREER Award (PI: Jewell) 03/14-02/19 “Dissecting the role of biomaterials in lymph nodes to study and shape immunity”
(5) Alex’s Lemonade Stand Foundation “A” Award (PI: Jewell) 01/14-01/17 “Engineering the lymph node environment with therapeutic vaccine depots to combat neuroblastoma”
3. ORIGINAL RESEARCH ABSTRACT SUBMITTED WITH THE STARTER GRANT PROPOSAL
Therapeutic vaccines for cancer and autoimmune disorders would benefit from approaches which allow delivery of vaccines and drugs that direct – or modulate – immune cell populations toward specific functions. This proposal is based on direct lymph node delivery of degradable, biomaterial vaccine depots that locally release immunomodulatory cargos to lymph node- resident immune cells. Our preliminary data demonstrate that lymph node deposition of vaccine depots loaded with different concentrations of a small molecule immunomodulator (rapamycin) can be used to generate immune populations with either immunostimulatory or regulatory phenotypes. Building on these studies, the first aim tests depots containing high doses of rapamycin and myelin auto-antigens indicated in multiple sclerosis pathogenicity to determine if these materials could help combat autoimmune disorders by decreasing TH1/TH17 function and increasing TREG/TH2 regulatory functions. A parallel aim tests depots loaded with tumor antigens and low doses of rapamycin as a therapeutic cancer vaccine to determine if these biomaterials generate antigen-specific central memory T cells (TCM) which are indicated in breaking tumor tolerance. Ultimately, this strategy could lead to new therapeutic vaccines that generate tolerizing immune responses for autoimmune disorders or potent immune responses for cancer therapy, depending on the dose and combination of immunomodulators in the vaccine depots.
4. SUMMARY OF ACIVITIES CARRIED OUR DURING THE AWARD PERIOD
During 2013 the pharmaceutics starter grant provided invaluable support for pilot studies the Jewell lab conducted to study the interactions of biomaterial with lymph nodes – the tissues that direct immune response. This work occurred in two major areas: i) fundamental studies to tease out the role biomaterials carriers play in modulating the structure and signaling in lymph nodes during vaccination, and ii) application of this idea for therapeutic vaccines in the areas of cancer and autoimmunity. On the fundamental side, studies investigated the effects of materials on lymph node structure by introducing polymeric micro- and nanoparticles into lymph nodes using a direct delivery platform recently developed by Dr. Jewell. The ability of these materials to activate primary dendritic cells was characterized in the absence or presence of adjuvants. These efforts resulted in the lab’s first independent paper, a report detailing the method we have developed for delivering polymer particles, adjuvants, and peptide antigens to lymph nodes.
The Pharmaceutics Starter Grant also supported pilot translational studies aimed at exploiting the lymph node delivery platform for cancer and autoimmune therapy. In the cancer studies, the grant supported establishment of a mouse model of neuroblastoma, a serious pediatric cancer. This model was used to if polymer particles loaded with tumor antigens and small molecular drugs could be used to polarize T cell effector compartments during primary and secondary tumor challenges. In the area of autoimmunity, support from the PhRMA foundation helped established a mouse model of multiple sclerosis in the lab for testing the hypothesis that local remodeling of the lymph node microenvironment allows generation of antigen-specific tolerance during autoimmunity.
