Research in the Wedel Lab relates to the understanding of regulatory T cell (Treg) function and lineage stability. Our studies include the discovery of intrinsic modulatory signaling networks that promote the resolution of inflammation in conventional T cells and/or optimize Treg function. Identifying novel immunomodulatory drug targets and strategies are essential to improving transplant outcomes because current immunosuppressive regimens fail to resolve persistent anti-donor responses. New therapeutics can be optimized to induce immune tolerance and thus long-term graft survival.
Active projects include:
1. T regulatory cell biology: CD4+ T regulatory cells (Tregs) are specialized subpopulations of CD4+ T cells that can suppress inflammation. Physiologically, Tregs maintain immunological homeostasis by resolving inflammation and preventing overwhelming immune responses to protect from autoimmunity. The Wedel Lab studies how intrinsic signaling networks within Tregs direct important milestones of Treg biology: Treg induction, immunomodulatory activity, Treg subset differentiation and/or Treg dedifferentiation into pro-inflammatory exTregs. We use cutting-edge multiomic screening platforms to dissect intrinsic signaling networks and to understand how Tregs can be controlled to ultimately suppress/resolve (allo-)immune responses. The goals of these studies are to identify novel molecular interactions that can be pharmacologically targeted to enhance immunoregulation following organ transplantation and promote the induction of operational tolerance (acceptance of the transplant in the absence of immunosuppressive drugs).
2. Omics research: The Wedel Lab explores transcriptional programs, ligand-receptor interactions and intrinsic signaling networks within the intragraft microenvironment, secondary lymphoid organs, and immune cells in the peripheral blood of humans and in vivo animal models, that developed transplant tolerance, have stable graft function or during active transplant rejection. By understanding mechanisms that are important for the modulation of alloimmune responses, we can identify central signaling nodes and molecular switches that are powerful to shift inflammation to immunoregulation. Our goals include the identification of central immunomodulators that target protolerogenic signaling networks in different cell types that are powerful to induce immunological tolerance following organ transplantation.
3. Translational and clinical studies: The Wedel Lab is particularly interested and committed to translate findings into therapeutics that can improve long-term graft function and quality-of-life post-transplantation. We are part of a national multi-center clinical trial where we plan to explore immunomodulatory molecules and alloimmune mechanisms following a novel pro-tolerogenic therapy in pediatric kidney transplant recipients. Additionally, we utilize collected datapoints in machine learning approaches and generate data-driven algorithms that will support future clinical decision making in pediatric transplant recipients (“transformative care”).
The Wedel Lab also participates in patient-centered initiatives (Clusters of Clinical Excellence) where we collaborate with multiple labs to study immune responses in immunocompromised patients, including pediatric transplant recipients. We bring our expertise in transplant immunology, assay development and omics-based research to a multidisciplinary team with the goal to identify strategies on how to optimize protective immune responses in immunocompromised pediatric patients.