IMMUNOLOGY, INFLAMMATION, PATHOBIOLOGY | BIOENGINEERING
The areas of research interest of the Chong laboratory include:
1. Transplantation tolerance.
2. Infections in Transplantation.
3. Immunobiology of humoral immunity in transplantation.
4. A multidisciplinary effort to develop adjuvant-free vaccines for infectious diseases.
Researchers in the Chong lab use a combination of in vivo mouse models of solid organ transplantation and infectious pathogens, cutting-edge cellular immunology techniques, in vivo imaging, as well as molecular and systems biology to understand the immunobiology of transplantation rejection and tolerance, and to investigate new approaches for vaccine development. Research in the Chong lab has been continuously supported by multiple grants from the National Institutes of Health for over 23 years.
Transplantation tolerance: The induction of tolerance is a major area of research in the Chong lab, as well as in the global transplantation research community. Currently, transplant patients have to take pharmacological drugs to non-specifically suppress their immune system in order to prevent rejection. This approach, while effective, results in unwanted drug side effects and increased susceptibility to infections and malignancies. One way to avoid the need for life-long immunosuppression is to induce a specific change in the immune system so that the transplant recipient becomes tolerant to the transplanted grafts but retains normal immune responses to infections and malignancies. The Chong lab is testing therapeutic approaches for inducing transplantation tolerance in experimental models, as well as using these models to understand how tolerance is achieved, maintained and diagnosed. The long-term goal is to translate these findings to the clinic.
Infections and Transplantation: It is not sufficient that transplantation tolerance is successfully induced; it is critical that tolerance persists for the life of the transplant recipients. Indeed, clinical data suggests a correlation between infections and graft rejection. The Chong lab, in collaboration with the laboratory of Dr. Marisa Alegre, has determine that some types of bacterial infections can destabilize or even override established tolerance, and precipitate the acute rejection of the allograft. Even more intriguing is our recent observations that this loss of tolerance can be transient, and contradicts a central immunological paradigm that rejection results in sensitization and memory that was established over 70 years ago. Researchers in the Chong and Alegre labs are investigating the mechanism for this memory of tolerance that dominates of the memory of rejection, and hope to apply these insights towards understanding and improving the resilience of tolerance.
Humoral immunity and antibody-mediated rejection: Antibody-mediated rejection is currently the main cause for the loss in function of transplanted organs, especially for sensitized patients that have developed graft-specific antibodies prior to transplantation. Thus there is a strong need for new approaches that can limit antibody production that damages the graft but yet retains antibody responses that confer protection to infections. The Chong lab has recently developed new transplantation models to study graft-specific B cell responses and to identify therapies that limit these responses and yet permiting sufficient immune responses to develop against viral and bacterial infections.
Vaccine development with nanoparticles: Our interest in infections in the transplantation has led to two collaborations with faculty at the University of Chicago. Studies on the immunobiology of methicillin-resistant Staphylococcus aureus in humans and in mouse models are conducted in collaboration with the Daum and Montgomery laboratories. We are particularly interested in defining, initially in mouse models, the antigens in S. aureus that elicit protective T cell and B cell responses and then testing whether these responses are lacking in patients that succumb repeatedly to S. aureus. The long-term goal of these studies is to translate these findings to the development of an efficacious S. aureus vaccine.
Complementing these studies is a new area of investigation between the Chong and Collier laboratories that aim at applying new nanotechnologies to developing adjuvant-free vaccines for infectious diseases. The Collier laboratory has developed self-assembling protein nanofibers that have an unusually potent ability to stimulate immune responses without exogenous adjuvants. We have been working to understand the mechanisms of immune stimulation as well as to optimize this platform to specific the type of immune responses that best controls specific infections. For instance, we are designing vaccines for viral infections that require both antibody and Th1 responses and for S. aureus infections that require antibody responses and Th17 responses.