Hugo Ramón Rosen, MD
Year elected: 2008
Current membership category: Senior
Hepatitis C is a leading cause of morbidity and mortality throughout the world. Our translational research laboratory focuses on understanding the innate and adaptive multi-cellular correlates of recovery versus viral persistence/liver injury. We utilize three human models: acute infection, liver transplantation, and therapy-induced remission. We have demonstrated the importance HCV-specific CD4+ T help in containing viral escape, that down-regulation of IL-7R alpha on CD4+ and CD8+ T lymphocytes early in HCV infection predates the development of persistence, that establishment of persistence is linked to suppressive function of Tregs, and have defined a novel role for cytotoxic CD56 positive NT cells in acute HCV infection. By characterizing responses to the entire HCV genome, we have identified immunogenic regions of potential importance for vaccine design. The natural history of HCV following liver transplant may be accelerated, providing a compelling framework for studying pathogenesis. We provided the first evidence for reconstitution of HCV-specific CTLs following liver transplantation and that the human liver allograft can prime novel CTLs. Understanding how recipient T cells can provide viral-specific immunity across HLA mismatch is an important step towards developing novel immunotherapeutics in this challenging setting. We have also examined the cellular basis for racial differences in HCV infection and differential rates responsiveness to antiviral therapy. African Americans demonstrate diminished HCV-specific T cell immunity, and, importantly, the level of T cell immunity predicts response to therapy. We have found that programmed death (PD)-1 expression on HCV-specific CTLs predicts failure of early and sustained virologic response to standard therapy.
University of Southern California Keck School of Medicine (Primary)
Janos Peti-Peterdi, MD, PhD is the representative at this institution.