Research in my lab is centered on understanding the basic principles of cellular processes, including: apoptosis and autophagy, cell cycle regulation and genomic stability, as well as intracellular membrane trafficking in the development of cancer and infectious disease.
As a lysosome-dependent quality control mechanism, autophagy (Greek for self-eating) has been increasingly recognized as essential for cellular homeostasis and for protection against diverse pathogens and cancer. We have for the first time identified UVRAG (UV Radiation Resistance Associate Gene) as a robust autophagy activator and tumor suppressor. Using cutting-edge technologies including: proteomic study, confocal/live cell imaging, cell culture and murine models, we have been able to demonstrate the roles for UVRAG in autophagy, membrane trafficking, and in tumor development (refer to NCB 2006 8(7): 688-699; NCB 2008 10(7): 759-61; Current Opinion in cell biology 2010 22(2): 226-33). We will continue to probe the underlying mechanisms of UVRAG-mediated autophagy and genomic stability in restricting tumor growth and in tumor response to cancer therapy.
Furthermore, we established that the viral Bcl-2 (vBcl-2) homolog of the g-Herpesviruses (g-HVs) family suppresses autophagy by directly targeting a key autophagy effector protein, Beclin1. The viral homologs (vBcl-2) of g-HVs have evolved enhanced anti-autophagic activity compared to their host counterpart (PLoS Pathogen 2009 5(10)). We investigated the functional significance and distinct contribution of virus-mediated autophagy and apoptosis inhibition in viral virulence. We will continue our rigorous efforts in a further exploration of the complex interactions between cellular safeguard processes vs. viral entry, infection, and pathogenesis.
We believe our studies will not only unravel the molecular bases of essential, routine cellular process, but also help translate these discoveries into more effective cancer and antiviral therapies.
Department of Molecular Microbiology & Immunology
Los Angeles, CA
Stony Brook, NY