(3bv) Exploiting Synthetic Materials to Study and Direct Immune Response

Over the past several decades, synthetic materials have contributed dramatically to new prophylactic and therapeutic treatments for a range of illness and disease, but drug delivery – the time, concentration, location, and specificity with which biological cargo is delivered – continues to be a major obstacle for medicine. My research interests have focused on designing and exploiting synthetic materials to achieve increased levels of control over the delivery of biological cargo. During this poster session I will highlight examples from my graduate and postdoctoral research which demonstrate the utility of synthetic biomaterials for enhancing the delivery of drugs, proteins, and nucleic acids in vitro and in vivo, and more recently, in the context of translational research focused on vaccination and immunotherapy. Building on this past work, I will describe my plans to nucleate a distinct, independent research program at the interface of immunology and materials engineering.

I completed doctoral studies at the University of Wisconsin – Madison under the guidance of Professor David Lynn in the department of Chemical and Biological Engineering. One major research area centered on development of degradable multilayered films that permit spatial or temporal control over the delivery of DNA and proteins from the surfaces of biomedical devices such as intravascular stents. In collaboration with the Abbott research group at UW, I initiated a parallel project aimed at exploiting the properties of a redox-active ferrocene-containing lipid to reversibly control DNA interactions using chemical and electrochemical cues. In October 2009 I accepted a postdoctoral fellowship from the Ragon Institute of MGH, MIT, and Harvard, initiating postdoctoral research with Professor Darrell Irvine at MIT. My postdoctoral work focuses on enhancing vaccination by exploiting the properties of biomaterials to increase the persistence of vaccine components in lymph nodes – the key site of immune response generation – and to engineer specific immunological profiles by controlled release of small molecules (immunomodulators) known to bias immune response.

A central theme of my research is application of basic science to develop new technologies, which is illustrated by my past projects in drug delivery that have generated 4 patent filings and 21 peer-reviewed publications. Immunology is an area flush with opportunities to apply biomaterials in the study of basic questions and to develop new strategies for improving human health. My expertise in biomaterials design, immunology, and vaccinology uniquely positions me to capitalize on these opportunities. The overarching goal of my research lab will be to exploit biomaterials to generate immune responses with specific, tunable characteristics. This concept has two research thrusts: 1) basic investigations aimed at understanding interactions between synthetic materials and key immune cells, and 2) development of biomaterial vaccines to combat infectious diseases and autoimmune disorders.

Related References:

(1)       C. M. Jewell*, J. Jung*, R. P. Carney, F. Stellacci, and D. J. Irvine, “Oligonucleotide delivery by cell-penetrating “striped” nanoparticles.” 2011 – In revision.

(2)       C. M. Jewell, S. C. Bustamante López, and D. J. Irvine, “In situ engineering of the lymph node microenvironment via intranodal injection of adjuvant-releasing polymer particles.” Proc. Natl. Acad. Sci. USA 2011 – In press.

(3)       C. M. Metallo, P. A. Gameiro, E. L. Bell, K. R. Mattaini, J. Yang, K. Hiller, C. M. Jewell, Z. R. Johnson, D. J. Irvine, L. Guarente, J. K. Kelleher, M. G. Vander Heiden, O. Iliopoulos, and G. Stephanopoulos, “Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia.” Nature 2011 – In press.

(4)       D. J. Irvine and C. M. Jewell, “Vaccine and Immunotherapy Delivery.”, Comprehensive Biomaterials, Ed. P. Ducheyne, Elsevier Press, 2011 – In press.

(5)       R. M. Flessner, C. M. Jewell, D. G. Anderson, and D. M. Lynn, “Degradable Polyelectrolyte Multilayers that Promote the Release of siRNA.” Langmuir 2011, 27, 7868-7876.

(6)       A. S. Breitbach, A.H. Broderick, C. M. Jewell, S. Gunasekaran, Q. Lin, D. M. Lynn, and H. E. Blackwell, “Surface-mediated release of a synthetic small-molecule modulator of bacterial quorum sensing: Gradual release enhances activity.” Chemical Communications 2011, 47, 370-372.

(7)       B. Sun, R. M. Flessner, E. M. Saurer, C. M. Jewell, N. J. Fredin, and D. M. Lynn, “Characterization of pH-induced changes in the morphology of polyelectrolyte multilayers assembled from poly(allylamine) and low molecular weight poly(acrylic acid).” Journal of Colloid and Interface Science 2011, 355, 431-441.

(8)       N. J. Fredin, R. M. Flessner, C. M. Jewell, S. L. Bechler, M. E. Buck, and D. M. Lynn, “Characterization of nanoscale transformations in polyelectrolyte multilayers fabricated from plasmid DNA using laser scanning confocal microscopy in combination with atomic force microscopy.” Microscopy Research and Technique 2010, 10.1002/jemt.20830.

(9)       E. M. Saurer, C. M. Jewell, J. M. Kuchenreuther, D. M. Lynn, “Assembly of Erodible, DNA-Containing Thin Films on the Surfaces of Polymer Microparticles: Toward a Layer-by-Layer Approach to the Delivery of DNA to Antigen-Presenting Cells.” Acta Biomaterialia 2009, 5, 913-924.

(10)   C. M. Jewell, M. E. Hays, Y. Kondo, N. L. Abbott, and D. M. Lynn, “Chemical Activation of Lipoplexes Formed from DNA and a Redox-Active, Ferrocene-Containing Cationic Lipid.” Bioconjugate Chemistry 2008, 19, 2120-2128.

(11)   C. M. Jewell and D. M. Lynn, “Surface-Mediated Delivery of DNA: Cationic Polymers Take Charge.” Current Opinion in Colloid and Interface Science 2008, 13, 395-402.

(12)   C. M. Jewell and D. M. Lynn, “Multilayered Polyelectrolyte Assemblies as Platforms for the Delivery of DNA and Other Nucleic Acid-Based Therapeutics.” Advanced Drug Delivery Reviews 2008, 60, 979-999.

(13)   C. L. Pizzey, C. M. Jewell, M. E. Hays, D. M. Lynn, N. L. Abbott, Y. Kondo, S. Golan, and Y. Talmon, “Characterization of the Nanostructure of Complexes formed by a Redox-Active Cationic Lipid and DNA.” Journal of Physical Chemistry B 2008, 112, 5849-5857.

(14)   M. E. Hays, C. M. Jewell, Y. Kondo, D. M. Lynn, N. L. Abbott, “Lipoplexes Formed by DNA and Ferrocenyl Lipids: Effect of Lipid Oxidation State on Size, Internal Dynamics and Zeta-Potential.” Biophysical Journal 2007, 93, 4414-4424.

(15)   J. Zhang, S. I. Montañez, C. M. Jewell, D. M. Lynn “Multilayered Films Fabricated from Plasmid DNA and a Side-Chain Functionalized Poly(β-amino ester): Surface-Type Erosion and Sequential Release of Multiple Plasmid Constructs from Surfaces.” Langmuir 2007, 23, 11139-11146.

(16)   B. Sun, C. M. Jewell, N. J. Fredin, D. M. Lynn, “Assembly of Multilayered Films Using Well-Defined, End-Labeled Poly(acrylic acid): Influence of Molecular Weight on Exponential Growth in a Synthetic Weak Polyelectrolyte System.” Langmuir 2007, 23, 8452-8459.

(17)   M. E. Hays, C. M. Jewell, D. M. Lynn, N. L. Abbott, “Reversible Condensation of DNA using a Redox-Active Surfactant” Langmuir 2007, 23, 5609-5614.

(18)   C. M. Jewell*, S. M. Fuchs*, R. M. Flessner, R. T. Raines, D. M. Lynn, “Multilayered Films Fabricated from an Oligoarginine-Conjugated Protein Promote Efficient Surface-Mediated Protein Transduction.” Biomacromolecules 2007, 8, 857-863.

(19)   C. M. Jewell, J. Zhang, N. J. Fredin, M. R. Wolff, T. A. Hacker, D. M. Lynn, “Release of Plasmid DNA from Intravascular Stents Coated with Ultrathin Multilayered Polyelectrolyte Films.” Biomacromolecules 2006, 7, 2483-2491. 

(20)   C. M. Jewell, M. E. Hayes, Y. Kondo, N. L. Abbott, D. M. Lynn, “Ferrocene-Containing Cationic Lipids for the Delivery of DNA: Oxidation State Determines Transfection Activity.” Journal of Controlled Release 2006, 112, 129-138.

(21)   N. L. Abbott, C. M. Jewell, M. E. Hayes, Y. Kondo, D. M. Lynn, “Ferrocene-Containing Cationic Lipids: Influence of Redox States on Cell Transfection.” Journal of the American Chemical Society 2005, 127, 11576-11577.

(22)   C.M. Jewell, J. Zhang, N. J. Fredin, D.M. Lynn, “Multilayered Polyelectrolyte Films Promote the Direct and Localized Delivery of DNA to Cells.” Journal of Controlled Release 2005, 106, 214-223.                                                                                               

*These authors contributed equally