Research Summary
Studies of transcriptional elongation control have led to important discoveries with relevance to human cancer and infectious diseases. My work focuses on the mechanisms and factors affecting transcriptional elongation control of HIV-1 (Human immunodeficiency virus-1).
AIDS (Acquired immune deficiency syndrome) has long been one of the most significant infectious diseases in the world, causing immune deficiency, and leading to serious infectious complications. The principal impediment to eradicating the infection is the latent reservoirs of HIV-1, which can resuscitate once drug treatment is interrupted. So, how can we kill the latent HIV-1? In patients with access to therapy, drugs aimed at inhibiting HIV replication have some limited value. “Shock and kill” is a novel concept taken as a potential first step towards the cure. Control of HIV-1 transcriptional activation is a critical step in this process.
I am interested in exploring potential host factors influencing HIV transcriptional elongation. Tat, a small HIV protein but the sensitive switch for HIV transcription activation, was known to have several host cofactors to activate latency. One widely studied cofactor is P-TEFb, a positive transcriptional elongation factor, which has been proved to form a super elongation complex with ELL2, AFF4, ENL and AF9.The general problems I wish to address are: (1) Are there any other host factors responding to Tat-mediated action? (2) How do they combine with Tat to influence HIV transcription, and interact with P-TEFb?
Using biochemistry and molecular biology techniques, such as gene knockout/knockdown, site-specific mutagenesis, real-time RT-PCR, western-blot, immunoprecipitation, chromatin immunoprecipitation, mass spectrometry, and RNA seq, we first compared the discrepant proteins that interacted with the target genes under certain conditions, such as drug treatment or gene mutation, and then explored their exact roles in HIV transcriptional control, trying to explain the above objectives. We hope the work will deepen our understanding of fundamental aspects of transcriptional elongation control, and enable the development of novel therapeutic strategies to eradicate latent HIV reservoirs in infected patients.
Impact in China
AIDS/HIV has deprived millions of lives worldwide; also it is a tough problem in China. To date in China, an increasing number of AIDS patients have received anti-virus treatments and a growing number of scientists have devoted their research to AIDS/HIV, but we are still far from killing the virus effectively and thoroughly. At UC Berkeley, I have the opportunity to expand my skills and insights in understanding the control of HIV transcriptional elongation and exploring novel anti-HIV therapeutic strategies. In the future, I hope to use my research to develop clinical therapies and contribute to advancements in combating infectious diseases.
Publications
Yu D, Zhao L, Xue T, Sun B (2012). Staphylococcus aureus autoinducer-2 quorum sensing decreases biofilm formation in an icaR-dependent manner. BMC Microbiol 12:288.
Fang H, Yu D, Hong Y, Zhou X, Li C, Sun B (2013). The LuxR family regulator Rv0195 modulates Mycobacterium tuberculosis dormancy and virulence. Tuberculosis 93:425-431.
Hong Y, Zhou X, Fang H, Yu D, Li C, Sun B (2013). Cyclic di-GMP mediates Mycobacterium tuberculosis dormancy and pathogenecity. Tuberculosis93:625-634.