- PhD, Yale University, 1993
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.
- Lee S., Salwinski L., Zhang C., Chu D., Sampankanpanich C., Reyes N.A., Vangeloff A., Xing F., Li X., Wu T.T., Sahasrabudhe S., Deng H., Lacount D.J., Sun R., "An integrated approach to elucidate the intra-viral and viral-cellular protein interaction networks of a gamma-herpesvirus," PLoS Pathog. 2011 Oct;7(10):e1002297. Epub 2011 Oct 20.
- Leang R.S., Wu T.T., Hwang S., Liang L.T., Tong L., Truong J.T., Sun R., "The anti-interferon activity of conserved viral dUTPase ORF54 is essential for an effective MHV-68 infection," PLoS Pathog. 2011 Oct;7(10):e1002292. Epub 2011 Oct 6.
- Yu F., Al-Shyoukh I., Feng J., Li X., Liao C.W., Ho C.M., Shamma J.S., Sun R.S., "Control of Kaposi's sarcoma-associated herpesvirus reactivation induced by multiple signals," PLoS One. 2011;6(6):e20998. Epub 2011 Jun 28.
- Liu Y., Tian X., Leitner W.W., Aldridge M.E., Zheng J., Yu Z., Restifo N.P., Weiss R., Scheiblhofer S., Xie C., Sun R., Cheng G., Zeng G., "Polymeric structure and host Toll-like receptor 4 dictate immunogenicity of NY-ESO-1 antigen in vivo," J Biol Chem. 2011 Oct 28;286(43):37077-84. Epub 2011 Sep 7.
- Olson C.A., Adams J.D., Takahashi T.T., Qi H., Howell S.M., Wu T.T., Roberts R.W., Sun R., Soh H.T., "Rapid mRNA-Display Selection of an IL-6 Inhibitor Using Continuous-Flow Magnetic Separation," Angew Chem Int Ed Engl. 2011 Jul 14. (Epub ahead of print)
- Al-Shyoukh I., Yu F., Feng J., Yan K., Dubinett S., Ho C.M., Shamma J.S., Sun R., "Systematic quantitative characterization of cellular responses induced by multiple signals," BMC Syst Biol. 2011 May 30;5:88.
- Wu T.T., Liao H.I., Tong L., Leang R.S., Smith G., Sun R., "Construction and characterization of an infectious murine gammaherpesivrus-68 bacterial artificial chromosome," J Biomed Biotechnol. 2011;2011:926258. Epub 2010 Dec 9.
- Li X., Feng J., Sun R., "Oxidative stress induces reactivation of Kaposi's sarcoma-associated herpesvirus and death of primary effusion lymphoma cells," J Virol. 2011 Jan;85(2):715-24. Epub 2010 Nov 10.
- Ishikawa F.N., Curreli M., Olson C.A., Liao H.I., Sun R., Roberts R.W., Cote R.J., Thompson M.E., Zhou C., "Importance of controlling nanotube density for highly sensitive and reliable biosensors functional in physiological conditions," ACS Nano. 2010 Nov 23;4(11):6914-22. Epub 2010 Oct 28.
- Wu T.T., Blackman M.A., Sun R., "Prospects of a novel vaccination strategy for human gamma-herpesviruses," Immunol Res. 2010 Dec;48(1-3):122-46. Review.