PhD Proposal

Sangeetha Srinivasan
January 7th 2015, Wednesday, 11am-12:30pm
Howey (Physics) Bldg, room#S106

Advisor: 
Julia E. Babensee, PhD
Wallace C. Coulter Department of Biomedical Engineering
Georgia Institute of Technology and Emory University

Thesis Committee: 
Julie Champion, PhD
School of Chemical and Biomolecular Engineering
Georgia Institute of Technology and Emory University

Edward Botchwey, PhD
Wallace C. Coulter Department of Biomedical Engineering
Georgia Institute of Technology and Emory University

Susan Thomas, PhD
George W. Woodruff School of Mechanical Engineering
Georgia Institute of Technology and Emory University

Krishnendu Roy, PhD
Wallace C. Coulter Department of Biomedical Engineering
Georgia Institute of Technology and Emory University

Title: Biomaterial-Based Engineering of Dendritic Cell Environments for
Targeted Immune Tolerance Induction 

Autoimmune disorders are estimated to be among the top ten
leading causes of death among women of all ages below 65, for which
available treatments include systemic immunosuppressants that cause serious
long-term side effects. There is hence a growing interest to engineer
mechanisms of inducing target-specific immune tolerance with biomaterials
particularly professional antigen presenting cells namely dendritic cells
(DCs). DCs previously studied in the context of biomaterials have been
discovered to elicit differential responses to biomaterials suggesting that
materials on their own have the ability to stimulate specific DC phenotype.
As the phenotype of DCs is a key mediator of downstream adaptive immune
responses that lead to normal or aberrant immunity, there is increasing
interest in delineating the underlying mechanisms of material-cell
interaction. In this proposal, we initially investigate the role played by
DCs in the adjuvant effect shown by certain materials such as poly
lactic-co-glycolic acid (PLGA) and further exploit the differential nature
of the response towards agarose compared to PLGA, to develop solely
biomaterial-based methods in inducing antigen-specific immune tolerance in
an *in vivo* mouse model. Moreover, DCs can be locally treated with
specific immunomodulators rather than biomaterials to express a tolerogenic
phenotype that can trigger antigen-specific immunoregulation. As a second
and distinct approach, in this proposal, we examine the possibility of
developing the spatiotemporally controlled delivery of immunomodulators
from a single implantable biomaterial niche. The design of such a delivery
device would call for not only incorporating a strategy for DC phenotype
modulation but also a technique for promoting endogenous DC recruitment
upon *in vivo* implantation; thus it would enable the localized delivery of
factors while promoting systemic circulation of in situ primed DCs for
effective downstream immune function, a feature commonly lacking in
existing treatments of autoimmune diseases. Finally, the efficacy of this
technique will be assessed in the context of an autoimmune disease model,
to explore its potential use as a therapeutic cure for individuals with
autoimmune disorders.