Descripción del proyecto
Transplantation is a life-saving procedure for patients who suffer from end-stage organ failure. While the discovery of potent immunosuppression offers a solution to the previously insurmountable problem of organ rejection, transplant recipients still face substantial problems, including chronic rejection and adverse effects related to the chronic use of immunosuppressive drugs. Therefore, transplantation field’s ‘holy therapeutic grail’ is immunological tolerance induction without the need
for chronic immunosuppression.
Our recent work has identified innate immune responses, and in particular trained immunity, to play a critical role in transplantation. Based on compelling preliminary data, I hypothesize that trained immunity-induced myelopoiesis and hyperinflammation are proximal causes of T and B cell immunity and therefore are compelling therapeutic targets to induce immunological tolerance and significantly
improve allograft survival.
We will tackle the central hypothesis from the vantage points of medicine & immunology and biomedical engineering by pursuing two objectives: Objective 1 Medicine & Immunology – To mechanistically decipher innate immune responses and myelopoiesis in kidney transplant patients. Objective 2 Biomedical Engineering – To develop immuno-imaging and nanomedicine approaches that target innate immunity in transplantation. We have developed a comprehensive preclinical development program to evaluate these novel methods in a kidney transplant mouse model.
This Program’s successful completion will yield unique nanobiologic immunotherapies and immunoimaging strategies, which can be employed to take control of the innate immune response and promote allograft tolerance in transplantation, but can also be adopted to treat other conditions that are characterized by an exacerbated immune response, including infections, cancer and
cardiovascular diseases.