Research Overview
Major Project Milestones (last 5 years)
Demonstrated for the first-time HIV-1 downregulates the protein synthesis machinery of the infected lymphocytes, potentially interfering with the ability to mount a protective antiviral response. Determined the gene necessary is VPR, which is a viral pathogenicity determinant.
Discovered the mechanism for continued HIV-1 synthesis of viral proteins involves retention of nuclear cap-binding protein
Characterized the impact of host microRNA on HIV-1 and counter-measures by HIV-1 change the activity of a subset of host microRNAs
Discovered a new molecular rheostat governing synthesis of growth-control genes:
DHX9/RNA helicase A is necessary for translation of selected mRNAs
DHX9 is recruited to cognate mRNAs:
- At a structurally complex RNA element in 5' leader, which we call PCE (post-transcriptional control element: that is conserved in retroviruses that infect human and animal hosts
- The RNA-protein interaction between DHX9/PCE
facilitates protein synthesis of the cognate mRNA, while mutation of DHX9 or
PCE selectively inhibits their translation
- retroviruses that infect avian, bovine, feline, simian species
- human retroviruses, e.g. HIV-1, HTLV-1
- human and rat junD, proto-oncogene
