(7r) Induction of Tolerance or Immunity by Targeting Antigens to Specific Antigen Presenting Cells via Synthetic Polymeric Glycosylations

As a post doc in Dr. Jeff Hubbell’s Lab at the University of Chicago, my research has focused on the development of biomaterials that target antigens to specific antigen presenting cells (APCs) for the induction of immunological tolerance or immunity. To this end, I have developed a platform based on synthetic glycopolymers that when tethered to antigens via an intracellular self-immolate linker, target APCs and release antigens in their unmodified form, thus optimizing antigen uptake and presentation by APCs. In the case of Tolerance, autoimmune disorders are driven by aberrant auto-reactive T cell responses. For this reason, therapies that specifically ablate auto-reactive T cells, unlike current therapies that induce global immune suppression, would represent a major step forward in the treatment of autoimmunity. When synthetized from monomers composed of NAc-glucosamine, our glycopolymer-antigen conjugates target antigens to hepatic APCs, which naturally induce tolerogenic T cell responses upon antigen presentation. Antigen-poly(NAc-glucosamine) conjugates are able to knockout antigen-specific T cell responses, and thus prohibit the onset of experimental murine diabetes, as well as induce regulatory T cells that provide long-term antigen-specific tolerance in the same murine diabetes model. Using the same glycopolymer platform with monomers composed of mannose and an APC-activating co-monomer, we are able to efficiently target and activate dendritic cells, which present the delivered antigens to T cells in the presence of cellular signals that induce T cell activation. When tethered to a malaria antigen and delivered via subcutaneous injection, antigen-poly(mannose) conjugates induce robust CD4 and CD8 T cell responses and muster antibodies that prevent malaria infection in human hepatocytes. My lab will focus on the development of immuno-modulatory biomaterials that are capable inducing immunity to infectious disease and malignancy. In addition, we will focus on biomaterials based strategies that use cells from tissue donors to induce tolerance in transplant recipients and eliminate the need for a life-time of suppressive therapies.

Post Doc Funding: Whitaker International Scholars Award

PhD Research: Reactive oxygen sensitive biomaterials for the treatment diseases associated with intestinal inflammation, Georgia Institute of Technology: Bioengineering, School of Chemical Engineering. Advisor: Dr. Niren Murthy.

Master’s Research: Molecular thermodynamics of polymeric dendrimers, University of Oklahoma, Chemical Engineering and Material Science. Advisor: Dr. Lloyd L. Lee.

Teaching Interests:

In addition to performing research, I have a very diverse set of teaching experiences. As an undergraduate, I worked for a year as a solo English Teacher to high school and college level students in the town of Clermont-Ferrand, France. Then as a master’s student at the University of Oklahoma, I had the chance to TA both lab and lecture courses and was given the award as the best graduate TA during the Fall 2003 semester. After completing my master’s degree, I solo taught undergraduate math courses at Florida State University, while I applied to PhD bioengineering programs. My research background in molecular thermodynamics and chemical engineering core course work at Georgia Tech have endowed me with a strong mathematical background that will facilitate my teaching of core chemical engineering courses such as transport phenomenon, engineering math, design, and of course thermodynamics. In addition, my research involving organic synthesis, biomaterials, and protein engineering will enable me to teach and create a variety of electives that will be interesting to undergraduates and graduate students alike.

Selected Publications:

M. Damo, D.S. Wilson, E. Simeoni, J.A. Hubbell, “TLR-3 stimulation improves immunity elicited by dendritic cell exosome-based vaccines in a murine model of melanoma”, Sci. Rep. 5, 17622, (2015).

C.D. Herman*, D.S. Wilson*, K.A. Lawrence, X. Ning, R. Olivares-Navarrete, J.K. Williams, R.E. Guldberg, N. Murthy, Z. Swartz, B.D. Boyan, “Rapidly polymerizing injectable click hydrogel therapy to delay bone growth in a murine resynostosis model”, Biomaterials. 35, 9698, (2014). * Authors contributed equally to this work

R.E. Whitmire, D.S. Wilson, A. Singh, M.E. Levenston, N. Murthy, A.J. Garcia, “Self-assembling nanoparticles for intra-articular delivery of anti-inflammatory proteins”, Biomaterials. 30, 7665, (2012).

D.S. Wilson, G. Dalmasso, L. Wang, S. Sitaraman, D. Merlin, N. Murthy., “Orally delivered thioketal nanoparticles loaded with TNF-α-siRNA target inflammation and inhibit gene expression in the intestines”, Nat. Mater., 9, 923, (2010).

D.S. Wilson, L.L Lee, “Chemical Potentials and Phase Equilibria of Lennard-Jones Mixtures: A Self-consistent Integral Equation Approach”, J. Chem. Physics, 123, 44512, (2005).

D.S. Wilson, L.L. Lee, “Molecular Recognition and Adsorption Equilibria in Starburst Dendrimers: Gas Structure and Sensing via Molecular Theory”, Fluid Phase Equilibria, 228-229, 197, (2005).