Engineering Durable AS Immune Tolerance via Push/Pull Immunomodulation of Dendritic Cells

Tuesday, June 16, 2026

10:00 AM-12:00 PM

BIOMED PhD Research Proposal 

Title: 
Engineering Durable Antigen-Specific (AS) Immune Tolerance via Push/Pull Immunomodulation of Dendritic Cells

Speaker:
Sihan Jia, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University

Advisor:
Peter Deak, PhD
Assistant Professor
Department of Chemical and Biological Engineering
College of Engineering
Drexel University 

Details:
Autoimmune and inflammatory diseases arise when dendritic cells (DCs) drive antigen-specific effector responses rather than tolerance. Current tolerogenic DC strategies are limited by incomplete, unstable reprogramming and off-target immunosuppression. This proposal develops a Push/Pull Immunomodulation (PPI) platform that simultaneously suppresses pro-inflammatory activation (“push”) and reinforces tolerogenic, regulatory programming (“pull”) in DCs to induce durable, antigen-specific tolerance.

Using a high-throughput screen of 40,833 immunomodulator/PRR-agonist combinations, we identified lead PPI formulations that maximize the IL-10/TNF-α ratio and engage tolerogenic checkpoints, including PD-L1 and BTLA, as well as the tryptophan-kynurenine-AhR axis. These leads are validated in human monocyte-derived DCs against clinical comparators and delivered via PLGA microparticles and lymph-node-targeting liposomes to confirm antigen-specific regulatory T-cell induction, in vivo persistence, and trafficking. The central proposed aim tests whether antigen-loaded PPI-DCs establish durable, antigen-specific tolerance in vivo using the MOG35-55 experimental autoimmune encephalomyelitis model, assessing clinical protection, antigen-specific Treg induction, and bystander specificity.

Together, this work defines a generalizable, biomaterial-enabled approach to engineering long-lived antigen-specific immune tolerance.

Contact Information

Natalia Broz
njb33@drexel.edu