Mary Caitlin Sok

Ph.D. Proposal Presentation (RESCHEDULED)

Date: Tuesday, October 10th

Time: 12:00pm

Location: Suddath Seminar Room (IBB 1128)

Committee Members:

Edward A. Botchwey, PhD (Advisor)

Andrew B. Adams, MD, PhD

Julia E. Babensee, PhD

Andrew S. Neish, MD

Krishnendu Roy, PhD

Immunomodulatory Biomaterials for the Induction of Transplant Tolerance

A major challenge in the transplant field is achieving a fine balance between achieving sufficient immunosuppression to prevent donated tissue rejection while managing the many side effects that occur in both the acute and chronic timeframe after induction of immunosuppressive therapy. For example, there is an increased incidence of wound healing complications following transplant surgery compared to similar non-transplantation procedures. Innate immune cells including monocytes, macrophages, and dendritic cells have emerged as critical cellular mediators that can play a role in modulating the immune response to allograft towards tolerance and acceptance. The overall hypothesis for the proposed research is that local recruitment of tolerogenic subsets of macrophages, dendritic cells, and T cells via delivery of Aspirin-Triggered Resolvin D1 (AT-RvD1) and on-site education via IL-10 will promote graft tolerance and wound healing associated with transplantation. We will first investigate how local delivery of the lipid proresolving molecule AT-RvD1 regulates monocyte recruitment and impacts vascular remodeling after injury. Next, we will develop an immunomodulatory hydrogel capable of the dual delivery of IL-10 and AT-RvD1 and quantify the recruitment of tolerogenic subsets of innate and adaptive immune cells.  Finally, using a skin transplant model, we will investigate how local immunomodulation via biomaterial is able to direct the cellular response to allograft towards inducing tolerance.