Ren Sun, PhD

Dr. Sun's laboratory is currently investigating the tumorigenic nature of the herpesviruses, EBV and HHV-8. The Lab will integrate biology and nanotechnology to define the underlying mechanism, and develop new diagnostic and therapeutic approaches, with murine gammaherpesvirus 68(MHV-68) as an in vivo model. The lab has previously identified Rta, a molecular switch that disrupts latency and initiates the lytic cycle. Using genomic approaches, the lab will identify the downstream target genes, and the cellular signal transduction pathways that control the expression and function of Rta and determine the optimal combination of these cellular factors/pathways to most efficiently reactive the herpesviruses, using a microfluidic system consisting of nano transducers. The lab will also identify cellular genes that play a role in viral replication and investigate the underlying molecular mechanisms. Another aspect that has captured our interest is the replication mechanism of hepatitis C virus (HCV). The lab has recently conducted genome-wide mutagenesis to build a high-resolution functional map of the HCV genome, which lays the foundation for further mechanistic studies and discoveries of novel therapeutic targets. The other challenge the lab undertakes is to apply nanotechnologies in viral detection and therapy. Sun's lab plans to build linkers between proteins and nanowires or quantum dots, which will will allow the lab to detect various viruses simultaneously. In addition, to develop new anti-viral therapies, we will use microfluidics to select specific inhibitors of viral and cellular proteins.

Viral infections are associated not only with acute illnesses, but also chronic diseases. In contrast to the rapidly manifesting SARS, Epstein-Barr virus (EBV) and Kaposi's Sarcoma-associated Herpesvirus (KSHV) are associated with several malignancies. To understand the molecular mechanism of viral replication and its role in pathogenesis, we are pursuing our research in the following directions. 1) We have identified a viral gene, which can initiate the complete lytic replication cascade of KSHV. We are addressing the questions of how it controls the expression of downstream genes and how cellular signal pathways control the viral switch. 2) We will determine the optimal combination of these cellular factors/pathways to most efficiently reactive the herpesviruses, using a microfluidic system consisting of nano transducers, which will be capable of sensing, making logical decisions, and providing real-time feedback control. 3) Murine herpesvirus-68 (MHV-68) is utilized as an in vivo model to dissect the roles of virus-encoded cytokines in viral replication and tumor-pathogenesis. 4) We take genomic, proteomic, and structural biology approaches to define the structure and function of viral proteins encoded by MHV-68 and SARS coronavirus. 5) We are initiating clinical trials by intentionally activating viral lytic gene expression in tumor cells to destroy tumor lesions. We will use molecular imaging technologies (PET, CT and CCD) to monitor viral replication and immune responses in mice and patients.