KSHV pathbiology and the role of AAA+ ATP-ases in nuclear signaling pathways
The main focus of our research is to understand the various mechanisms employed by the KSHV virus to subvert its host leading to Kaposi's Sarcoma, the most common form of AIDS related cancer, using a range of structural and biochemical/biophysical techniques. We have a particular interest in how KSHV is able to hijack the NF-kB transcriptional pathways that are essential for survival/proliferation together with its capacity to initiate a process termed "host shut off" in which 80% of all host mRNA transcripts are degraded (also a key factor in pathogenesis). Having identified and confirmed the roles of essential proteins that participate in these mechanisms, we are also seeking ways in which they may be exploited for the design and synthesis of novel therapeutics. In addition to KSHV pathobiology, we also have interests in hexameric AAA+ ATP-ases and their roles in chromatin remodeling, DNA repair, transcription and gene expression. This necessarily involves the recognition and modulation of specific target DNA sequences as well as the recruitment of various interacting partners and transcription factors. Our particular interest is the participation of AAA+ ATP-ases in nuclear wnt signaling pathways and the processes underlying promoter activation that are poorly understood, but have important implications in disorders ranging from diabetes to the majority of human cancers.
