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Department of SurgeryWelcome to The Chong Lab
The induction of immunological tolerance to transplanted organs is a central research focus of the Chong lab. Since the early 1990s, my laboratory has been dedicated to unraveling the underlying mechanisms of transplantation tolerance. We are continuing our 20+ year collaboration with Dr. Marisa Alegre (Department of Medicine, U Chicago) to study how infections and prior sensitization events prevent the induction of stable transplantation tolerance in mouse models. Our long-term goals are to develop better strategies to induce, maintain, and diagnose tolerance in transplant recipients. The ongoing research is focused on investigating how pregnancy imprints T cell tolerance to subsequent offspring-matched heart grafts, and how memory T cells can be reprogrammed to acquire susceptibility to transplantation tolerance.
My laboratory focuses on investigating the immunobiology of memory alloreactive B cells and plasma cells. Our main objective is to develop targeted strategies for treating antibody-mediated rejection (AMR) and reversing humoral sensitization. To achieve this, we utilize experimental rodent models for fundamental mechanistic research, and are translating these findings into the clinic. We are partnering with Dr. Marlena Habal, a clinician scientist from New York University, to conduct innovative clinical trials and mechanistic studies to identify effective treatments for highly sensitized individuals, particularly multiparous women. Additionally, we have a collaboration with Dr. Marcus Clark from U Chicago, where together, we are using novel multiparameter imaging to identify functional immune architectures to gain insights into the pathogenesis of rejection in human transplant recipients. These collaborative projects allow us to bridge the gap between fundamental research and its potential application in clinical settings.
A third area of my research interest stems from a longstanding collaboration of over 10 years with Dr. Joel Collier, a bioengineer at Duke University, and Dr. Anne Sperling, a lung immunologist at The University of Virginia. This project is dedicated to developing non-inflammatory and needle-free nanoparticulate vaccines that can provide protection against respiratory infections. My laboratory is focused on elucidating the mechanisms by which antigen-displaying nanofibers induce dendritic cell activation and the generation of lung-specific CD4+ and CD8+ T cell effector and memory responses.
If you want to answer a simple question, go alone; if you want to answer a complex question, go together.
Our Current Projects
Gain an insight into our current projects
Reprogramming hypofunction in memory T cells to achieve transplantation tolerance
We are investigating the mechanisms of novel reprogramming, using classical cellular in conjunction with high-dimensional multi-omics approaches.
Desensitizing humoral responses to increase access to transplantation
The long-term goal of this project is to improve access to transplantation in historically-disadvantaged multiparous women, as well as to optimize their post-transplant outcomes through the prevention and reversal of pregnancy-induced humoral sensitization.
Autoreactive B cells and antibodies in antibody-mediated rejection
Our investigation into the specificity of B cells infiltrating biopsies diagnosed with antibody-mediated rejection indicate that these B cells were not donor-HLA reactive, but unexpectedly, they were predominantly autoreactive. This bedside-to-bench project aims to understand the immunobiology of autoreactive antibody production and their role in antibody-mediated rejection.
Redefining clinical rejection with highly multiplexed spatial profiling
This project ultimately aims to improve the diagnosis of rejection. We will also use this information to develop more clinically-relevant mouse models to study mechanisms of kidney rejection, with the eventual goal of identifying therapies for individualized treatment of rejection in the clinic.
Nanoparticle adjuvant-free vaccines
We are currently conducting mechanistic investigations with these nanofibers appended with T cell epitopes, and using mouse models or human organoid cultures, focusing on their effects on dendritic cells and T cells and in the context of influenza infection. We aspire that these investigations will lead to a new framework for designing safe and efficaciously inhaled needle-free vaccines to protect against respiratory infections.