Molecular Biology and Genetics
Our laboratory is studying the epigenetic basis of normal development and disease, including cancer, aging, and neuropsychiatric illness. Early work from our group involved the discovery of altered DNA methylation in cancer, as well as common epigenetic (methylation and imprinting) variants in the population that may be responsible for a significant population-attributable risk of cancer. Over the last few years, our laboratory has pioneered the field of epigenomics, i.e.
The ribosome is the macromolecular complex that translates the genetic code into functional polypeptides. We are interested in how this ribonucleoprotein (RNA + protein) machine catalyzes and coordinates the complex molecular events of translation. Current work in the Green lab ranges all the way from translational initiation mechanisms in bacteria to ribosome homeostasis in human disease. In all of our projects, we rely on biochemical methods, using in vitro translation systems fully reconstituted from bacterial and yeast components.
The laboratory is interested in molecular and genetic mechanisms responsible for development of the immune system. The generation of immunologic diversity provides a spectacular example of genomic plasticity in the form of V(D)J recombination. This process, which builds antigen receptor genes from discrete gene segments, is a potential source of DNA damage and is subject to tight control. One control mechanism, identified in this laboratory, restricts V(D)J recombination to a specific time in cell cycle through the periodic destruction of the V(D)J recombinase.
Eucaryotic RNA polymerase II is unique among RNA polymerases in containing an unusual repetitive domain at the C-terminus of the largest subunit. This C-terminal domain (CTD) is comprised of tandem repeats of the consensus sequence TyrSerProThrSerProSer. We are using genetic and biochemical approaches to investigate the functional role of the CTD in biogenesis of mRNA. Both yeast and mammalian systems are being employed. A major effort in the lab is directed at studies of proteins that bind the CTD.
Telomeres protect chromosome ends from being recognized as DNA damage and chromosomal rearrangements. Conventional replication leads to telomere shortening, but telomere length is maintained by the enzyme telomerase that synthesizes telomere sequences de novo onto chromosome ends. Telomerase is specialized reverse transcriptase, requiring both a catalytic protein and an essential RNA component. In the absence of telomerase, telomeres shorten progressively as cells divide, and telomere function is lost.
Research in the Retrovirus Laboratory focuses on the molecular virology and pathogenesis of lentivirus infections. In particular, the simian immunodeficiency virus (SIV) is used to examine the molecular basis for the pathogenesis of HIV CNS disease. Research projects include studies of viral molecular genetics and host cell genes and proteins involved in the pathogenesis of disease. Further studies of lentivirus infections of macrophages and specific viral pathogenesis in the central nervous system and the lung are of interest.