In conjunction with our main project on PPI inhibitors, we are also interested in developing a system to systematically ablate or modulate antigen presenting cells (APC) during transplantation. Our main question is: which APC is most critical for generating a rejection response to a vascularized skin transplant? Research has shown that nearly all subsets of APCs (monocytes, neutrophils, DCs, macrophages, NK cells) play some role in the process of rejection, but which is most critical? We will design targeted nanoparticles for each subset and load them with drugs to either inhibit or modulate the response of each APC subset. Next, we will use mouse transplant models to systematically rank the relative value of each APC. This will not only provide a potential therapy for transplant rejection prevention, but also guide future research in transplant rejection.
