- Edward G. Elcock Professor of Surgical Research
- Chief of Organ Transplantation, Department of Surgery
- Director, Comprehensive Transplant Center
PhD (2008), University of Oxford, UK
There is a growing appreciation that injuries occurring shortly after organ transplantation can set in motion a cascade of events that contribute to long-term graft dysfunction. For example, during ischemia-reperfusion injury (IRI), endothelial cells lining the graft vasculature are subjected to oxidative stress and mitochondrial dysfunction, resulting in chronic transplant dysfunction. Therefore, targeting these cells to minimize early graft injury and mitigate immune recognition can provide a viable pre-treatment strategy.
To this end, our group has developed a novel Targeted Rapamycin Micelle (TRaM) nanoparticle decorated with cyclic peptide moieties to target receptors on the endothelial cells. The targeting moiety significantly improved TRaM uptake and downregulated the production and release of pro-inflammatory cytokines in injured cells. Furthermore, pre-treatment of endothelial cells with the nanoparticles was associated with the downregulation of memory T cell responses, a crucial player involved in acute rejection and spared during induction immunosuppression. Delivery of rapamycin through standard preservation solutions augmented with nanoformulations and targeted to specific cell types can blunt early IRI responses that occur upon implantation and promote allograft longevity.
Areas of Interest
Rapamycin, Immunosuppression, Endothelium, Immunometabolism, Nanotherapy, Micelle, Vasculopathy, Transplant